Diabetic kidney disease (DKD) is a common and serious complication of diabetes, affecting approximately 40% of patients with the condition. The pathogenesis of DKD is complex, involving multiple proce Show more
Diabetic kidney disease (DKD) is a common and serious complication of diabetes, affecting approximately 40% of patients with the condition. The pathogenesis of DKD is complex, involving multiple processes such as metabolism, inflammation, and fibrosis. Given its increasing incidence and associated mortality, there is an urgent need to identify novel pathogenic genes and therapeutic targets. This study systematically identified hub DKD-associated genes and their potential molecular mechanisms through bioinformatic analysis. Gene expression datasets from DKD patients and healthy controls were obtained from the GEO database. Hub genes were screened using differential expression analysis, weighted gene co-expression network analysis (WGCNA), LASSO regression, random forest (RF) algorithms, and consensus clustering for DKD patient classification. Additionally, immune cell infiltration analysis was performed on differentially expressed genes to explore the relationship between hub genes and the immune microenvironment. Potential drugs targeting LPL were predicted based on gene-drug interaction analysis. Immunohistochemistry was used to verify the expression of LPL and TNF-α in kidney tissues from patients with varying degrees of DKD severity, as well as their relationship with kidney function impairment. This study revealed that LPL, a lipoprotein metabolism gene, plays a crucial role in DKD, participating in cholesterol and glycerolipid metabolism as well as PPAR signaling. LPL expression was negatively correlated with pro-inflammatory M1 macrophages and various subsets of T cells, including naïve CD4 T cells and gamma delta T cells, while positively correlated with follicular helper T cells, suggesting its immune-regulation effects in DKD progression. Potential LPL-targeting drugs, such as Ibrolipim, anabolic steroid, and acarbose, might mitigate DKD. LPL expression was decreased with DKD severity and was correlated with TNF-α and kidney dysfunction markers, indicating its key role in DKD progression. LPL is a pivotal regulator of lipid metabolism and immune inflammation in DKD. Potential drugs targeting LPL offer new candidates for precision treatment of DKD. These findings lay a theoretical foundation for understanding the molecular mechanisms of DKD and developing LPL-based therapeutic strategies. Show less
Francesco Cavallieri, Francesco Bove, Alessandro Zampogna+11 more · 2025 · Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · Springer · added 2026-04-24
To identify preoperative clinical predictive factors of postoperative speech changes in Parkinson's disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Demograph Show more
To identify preoperative clinical predictive factors of postoperative speech changes in Parkinson's disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Demographic variables, neuroimaging data, and clinical characteristics were retrospectively collected from consecutive PD patients, before, 1 and 10-years after bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015. Predictors of postoperative speech changes (demographic, clinical and MRI variables) were assessed with univariate and multivariate logistic regression analyses. We considered as "event" a worsening of speech subscore (UPDRS item 18; MDS-UPDRS item 3.1) in the postoperative on-stimulation/off-medication (1-year follow-up) or under chronic treatment (10-years follow-up) conditions compared with the preoperative off-medication condition. 324 PD patients (males: 196; disease duration at surgery: 11.10 [± 4.13] years; age at surgery: 56.25 [± 8.52] years) were included in the analysis. Overall, the speech item of the clinical rating did not change in 138 patients (42.6%), it improved in 113 patients (34.9%) and worsened in 73 patients (22.50%) 1-year after surgery. The preoperative off-medication speech item score and the degree of motor improvement after surgery in the med-off condition predicted the 1-year postoperative speech change. In the long-term subgroup (n=51) the preoperative percentage of daily time spent with fluctuations was associated with long-term speech worsening. Effects of STN-DBS on speech can substantially vary in PD patients. Predictors of short-term speech deterioration appears to be related to preoperative off-medication speech impairment and degree of motor improvement after surgery. Show less
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatment Show more
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less
While a growing body of literature exists on initial word-to-meaning mapping and retrieval of fully lexicalized words, our understanding on the consolidation that occurs between these two stages remai Show more
While a growing body of literature exists on initial word-to-meaning mapping and retrieval of fully lexicalized words, our understanding on the consolidation that occurs between these two stages remains limited. The current study investigated the neural correlates of retrieving newly learned word using oscillatory brain dynamics. Participants learned to associate new words with unknown objects and performed overt and covert naming tasks during the first and last days of a five-day training period. Behavioral results showed improved overt naming on Day 5 compared to Day 1. Selecting only words that were successfully produced in the overt naming task, we examined oscillatory activity associated with word retrieval while participants produced new words covertly, both pre- (Day 1) and post (Day 5) learning. The results showed a robust alpha (8-12 Hz) and lower beta (13-25 Hz) power decrease during covert naming after learning. We hypothesize that this alpha-beta power decrease indexes successful word retrieval following consolidation. Show less
This study aimed to compare the safety profile of high-power (HPL) and low-power (LPL) Holmium:YAG lasers in retrograde intrarenal surgery (RIRS), using urinary Kidney Injury Molecule-1 (KIM-1) as an Show more
This study aimed to compare the safety profile of high-power (HPL) and low-power (LPL) Holmium:YAG lasers in retrograde intrarenal surgery (RIRS), using urinary Kidney Injury Molecule-1 (KIM-1) as an early biomarker for acute kidney injury (AKI). Sixty patients with renal stones (1.5-2.5 cm) were prospectively randomized into HPL and LPL groups. Urinary KIM-1 and KIM-1/creatinine ratios were measured preoperatively and at 4 and 24 h postoperatively. Intraoperative parameters, stone-free rates (SFR), complications, and renal function (eGFR, serum creatinine) were also assessed. Intrarenal temperatures were recorded before and after lithotripsy. Operative time, SFR, complication rates, and renal function parameters were similar between groups (p > 0.05). However, KIM-1 levels were significantly higher in the HPL group at 24 h postoperatively (278.8 ± 239.6 pg/mL vs. 170.3 ± 172.9 pg/mL, p = 0.003), and the KIM-1/creatinine ratio was also elevated (5.5 ± 4.5 vs. 3.1 ± 2.0, p = 0.035). No significant differences were observed in postoperative serum creatinine or eGFR. Intraoperative renal temperatures increased slightly in the HPL group, but the difference was not statistically significant. While high-power laser lithotripsy does not adversely affect global renal function, it is associated with elevated levels of renal injury biomarkers, suggesting greater subclinical renal stress. Show less
Biallelic pathogenic variants in the Genetic data were derived from a Polish cohort of 5623 whole exome sequenced patients. In 52 cases the indication for WES genetic testing was "hypertriglyceridemia Show more
Biallelic pathogenic variants in the Genetic data were derived from a Polish cohort of 5623 whole exome sequenced patients. In 52 cases the indication for WES genetic testing was "hypertriglyceridemia '' and for 5571 there was another clinical indication, mainly autism spectrum disorder, dysmorphia and neurodegenerative diseases. We present 22 heterozygous and 2 homozygous/compound heterozygous individuals for the pathogenic/likely pathogenic LPL variant and describe HTG levels, phenotypic manifestations and age of onset in the context of molecular findings where available. We report for the first time heterozygous LPL individuals with very severe HTG (TG ≥ 22.6 mmol/l; > 2000 mg/dl) and additional symptoms such as pancreatitis and recurrent abdominal pain. We argue that although the individuals carrying the single LPL pathogenic/likely pathogenic variant display the whole disease spectrum, the severe phenotype of heterozygotes with dominantly inherited LPL-related HTG may also exist. Show less
Lipoprotein lipase (LPL) is critical for clearance of circulating triglycerides and for tissue fatty acid supply. LPL is primarily synthesized and secreted by adipocytes into the interstitium and must Show more
Lipoprotein lipase (LPL) is critical for clearance of circulating triglycerides and for tissue fatty acid supply. LPL is primarily synthesized and secreted by adipocytes into the interstitium and must traffic from there to the abluminal/basolateral side of capillary endothelial cells. There, LPL binds glycosylphosphatidylinositol-anchored protein 1, GPIHBP1, which stabilizes the protein and facilitates its movement across the endothelial cells to the luminal side where it functions in hydrolysis of lipoprotein triglycerides. Importance of LPL traffic is supported by findings that rare mutations in GPIHBP1 cause hypertriglyceridemia. However our understanding of how LPL is secreted by adipocytes and traffics to endothelial cells is incomplete. Here we examined the possibility that secretion and traffic of adipocyte LPL might involve generation of small extracellular vesicles (sEVs/exosomes) which often mediate cell-cell communication. Proteomic analysis of sEVs secreted by adipocytes showed them enriched in LPL. To study LPL secretion and transfer we generated human derived pre-adipocytes (HPA) that stably express tagged LPL (FLAG and His epitopes). LPL pulldown and sEV isolation from HPA conditioned media documented that greater than 70% of secreted LPL is present in sEVs. The mechanism for LPL secretion in sEVs was found to involve the ESCRT-independent neutral sphingomyelinase 2 (nSMase2) pathway, as treatment with the nSMase2 inhibitor GW4869 reduced secretion by 80%. The above observations were reproduced using highly sensitive nanoparticle flow cytometry. The sEV associated LPL has lipolytic activity and it is released by heparin addition indicating it is on the sEV surface. In addition, using human derived microvascular endothelial cells with stable lentiviral expression of GPIHBP1 we show that LPL positive sEVs transfer LPL to these cells, but not to control cells without GPIHBP1. Our findings suggest that sEV formation by nSMase2 controls adipocyte LPL secretion and traffic, that sEVs protect LPL activity and facilitate LPL transfer to GPIHBP1 on endothelial cells. Show less
Lipoprotein lipase (LPL) is a triglyceride lipase that is contained in intracellular vesicles in an inactive storage form before secretion, but the precise structural details have not yet been resolve Show more
Lipoprotein lipase (LPL) is a triglyceride lipase that is contained in intracellular vesicles in an inactive storage form before secretion, but the precise structural details have not yet been resolved. Using cryo-electron tomography (cryo-ET), we observe that LPL exists inside of storage vesicles as a filament with an 11-nanometer diameter and is packed in these vesicles in two distinct patterns. Next, we solved a 4.2-Å resolution cryo-electron microscopy (cryo-EM) structure of this 11-nanometer LPL filament using purified protein. The filament is made of repeating pairs of LPL molecules with occluded active sites, rendering the LPL inactive. The comparison of the in situ subtomogram average and the in vitro cryo-EM structure indicates that the previously uncharacterized physiological storage form of LPL is an inactive filament. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of obesity and type 2 diabetes, can progress to metabolic dysfunction-associated steatohepatitis and fibrosi Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of obesity and type 2 diabetes, can progress to metabolic dysfunction-associated steatohepatitis and fibrosis. MASLD is characterized by elevated hepatic lipid accumulation (steatosis) and insulin resistance. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, induces hepatic insulin resistance and steatosis in animal models through unknown mechanisms. Herein, we investigated the mechanisms behind KD-induced metabolic dysfunction-associated steatohepatitis and fibrosis at thermoneutrality, identifying upregulated inflammatory and lipogenic pathways, including Il-6, Tnf, Mapk13, Lpl, and Pparg. Given the substantial increase in IL-6 during MASLD progression, we investigated IL-6-gp130 signaling using liver- and adipocyte-specific knockout mice. Liver-specific gp130 deletion failed to prevent KD-induced hepatic steatosis and glucose intolerance. In contrast, adipocyte-specific gp130 deletion significantly reduced KD-induced hepatic steatosis by suppressing lipolysis in white adipose tissue and reducing p-JNK and p-p38 signaling in the liver. In agreement, adipocyte-specific deletion of gp130 protected mice from KD-induced hepatic steatosis in response to recombinant IL-6 treatment. Our studies demonstrate the importance of adipose tissue-liver crosstalk in mediating MASLD progression and identify adipocyte IL-6-gp130 as a potential therapeutic target. Show less
Small ruminant lentivirus (SRLV) infections occur worldwide in goats and sheep and have negative impact on the production and welfare of animals. During recent years, many studies have focused on the Show more
Small ruminant lentivirus (SRLV) infections occur worldwide in goats and sheep and have negative impact on the production and welfare of animals. During recent years, many studies have focused on the host factors that determine the resistance of individual animals to SRLV infection; consideration of such factors would be an alternative to current control programmes based on culling seropositive animals. The aim of this study was to analyse the relationship between the expression of two previously selected goat genes, Primary fibroblast cultures obtained from the skin of goats with high SRLV proviral DNA load (HPL), low proviral load (LPL) or free of infection were inoculated with the A5 SRLV subtype circulating in the flock. The course of infection was observed based on cytopathic changes in cell cultures and the presence of SRLV A5 RNA, of which the level was monitored using a quantitative reverse-transcription PCR. The relative expression of the selected host genes following SRLV infection was analysed. The kinetics of SRLV replication differed, and distinctly higher numbers of SRLV particles were detected in cells derived from the HPL animal. The expression profiles of The observed relationship between expression of Show less
Familial chylomicronemia syndrome (FCS) is a rare monogenic disorder characterized by severe hypertriglyceridemia caused by pathogenic variants in genes involved in triglyceride metabolism. Glycosylph Show more
Familial chylomicronemia syndrome (FCS) is a rare monogenic disorder characterized by severe hypertriglyceridemia caused by pathogenic variants in genes involved in triglyceride metabolism. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of triglyceride-rich lipoproteins. We present 3 unrelated cases of FCS with a newly identified homozygous complex insertion-deletion variant in GPIHBP1, namely c.460₄₆₁delinsAAA, p.Ala154Lysfs*153. All 3 cases presented with severe hypertriglyceridemia, a high FCS clinical score, and significantly reduced lipoprotein lipase (LPL) activity (being 6.6 mUI the value corresponding to 20% of normal activity). These observations expand the spectrum of pathogenic GPIHBP1 variants in FCS. The identification of GPIHBP1 variant reinforces the causal link between GPIHBP1 mutations and LPL deficiency, as evidenced by diminished LPL activity, and further expands the genetic landscape of FCS. Show less
Alternative sources of dietary fish oil (FO) are necessary for the growth of the aquaculture industry. This study investigated the potential benefits of black soldier fly larvae oil (BSFLO) as a feed Show more
Alternative sources of dietary fish oil (FO) are necessary for the growth of the aquaculture industry. This study investigated the potential benefits of black soldier fly larvae oil (BSFLO) as a feed ingredient in the diets of African catfish hybrids ( Show less
Ruyun Gao, Ning Lou, Sheng Yang+7 more · 2025 · Clinical cancer research : an official journal of the American Association for Cancer Research · added 2026-04-24
Third-generation EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge Show more
Third-generation EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge. This study investigates the metabolic mechanisms driving third-generation EGFR-TKI resistance. We conducted plasma metabolomics analysis on 216 longitudinal samples from 186 patients with NSCLC enrolled in the clinical trial of rezivertinib (NCT03386955). Additionally, multiomics profiling of rezivertinib-resistant cell lines, functional in vitro experiments, and single-cell RNA sequencing analyses of 215 patients with NSCLC were integrated to reveal underlying mechanisms. Nonresponder patients exhibited elevated glycerophospholipids and dysregulated lysophospholipid (LPL) metabolism. Unsupervised clustering identified two patient subgroups, with cluster 1 (characterized by high LPL levels) associated with poorer survival (P = 0.022). A metabolite-based predictive model achieved robust performance [AUC: 0.7762 (training) and 0.7485 (test)]. Longitudinal analyses demonstrated LPLs and lysophosphatidic acid (LPA) accumulation during the resistance process. Integrated multiomics analyses highlighted epithelial-mesenchymal transition and glycerophospholipid reprogramming in rezivertinib-resistant cells. Functional assays confirmed that LPA promoted cell migration and invasion and attenuated the efficacy of third-generation EGFR-TKI, whereas disruption of the LPA-LPA receptor signaling axis reversed LPA-mediated resistance. Single-cell RNA sequencing identified an LPA-secreting malignant subset (cluster c4), characterized by enhanced epithelial-mesenchymal transition activation and extensive microenvironmental cross-talk through Wnt, TGF-β, and extracellular matrix signals. Our study highlights the pivotal role of LPA-mediated signaling and metabolic reprogramming in third-generation EGFR-TKI resistance. Targeting LPA production or its downstream pathways may offer novel therapeutic strategies to overcome resistance. This study provides critical metabolic insights for managing EGFR-mutant NSCLC. Show less
Breast cancer (BRCA) ranks among the most frequently diagnosed malignancies worldwide. Immune infiltration plays a critical role in tumor progression and therapeutic response. However, the precise mec Show more
Breast cancer (BRCA) ranks among the most frequently diagnosed malignancies worldwide. Immune infiltration plays a critical role in tumor progression and therapeutic response. However, the precise mechanisms underlying immune infiltration in BRCA remain incompletely understood. Machine learning (support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression) and weighted gene co-expression network were utilized to screen hub genes. An immune infiltration assessment was carried out via TIMER and CIBERSORT. The prognostic and survival of risk model and immune infiltration-associated hub genes were analyzed through Kaplan-Meier survival analysis, Cox regression, and ROC curve evaluation. Cell functional assays and xenograft models in vivo were utilized to examine lipoprotein lipase (LPL) function. The impact of LPL on macrophage polarization was evaluated using THP-1-derived macrophages and immunohistochemistry analysis of immune infiltration (CD4, CD8, and F4/80) in vivo. 10 hub immune regulators were identified in BRCA, which were associated with lipid metabolism. Hub genes and a prognostic risk model exhibited high predictive accuracy for BRCA patient survival and prognosis. Overexpression of LPL inhibited BRCA cell proliferation, migration, and invasion while promoting M1-like macrophage polarization. In vivo, LPL overexpression significantly suppressed tumor growth and enhanced immune cell infiltration, as indicated by the elevation of CD4 + and F4/80 + cells along with a decline in CD8 + macrophage abundance. This study identifies a novel lipid metabolism-related gene signature and demonstrates that LPL overexpression modulates macrophage polarization and inhibits BRCA progression. Show less
Physiology is closely synchronized to daily and seasonal light/dark cycles. Humans artificially extend daylight and experience irregular light schedules, resulting in dysregulation of metabolism and b Show more
Physiology is closely synchronized to daily and seasonal light/dark cycles. Humans artificially extend daylight and experience irregular light schedules, resulting in dysregulation of metabolism and body mass. In rodents, winter-like conditions (cold and short photoperiod) can alter energy balance and adipose tissue mass. To determine if photoperiod alone, independent of temperature, is a strong enough signal to regulate adiposity, we compared the effects of long and short photoperiod at thermoneutrality on adiposity and WAT gene expression in photoperiod-sensitive, F1 generation wild-derived adult male white-footed mice ( Show less
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs a Show more
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs and PLA-MPs were prepared, with PLA-MPs having a rougher surface and broader size distribution. In vitro, PLA-MPs showed higher cytotoxicity to granulosa cells compared to PS-MPs. In vivo, MPs exposure disrupted the estrous cycle, and damaged ovarian reserve. Granulosa cell apoptosis and cytokine activation led to transzonal projection retraction, oocyte oxidative stress, meiotic abnormalities, and reduced oocyte retrieval and polar body extrusion rate, thus reducing litter size. PS-MPs induced more severe intestinal and ovarian impairment. Analysis of feces 16S rRNA, serum metabolomics, and ovarian RNA sequencing revealed that lipoprotein lipase (LPL) was suppressed by both MPs, linking gut microbiota, lipid metabolism, and ovarian injury. Fecal microbiota transplantation as a rescue strategy in MPs exposed mice upregulated LPL, alleviating ovarian reserve decline. In PLA-MPs exposed mice, ovarian reserve related indicators partially recovered after a two-week exposure cessation. These results clarify the similarities and differences in how PS-MPs and PLA-MPs impair ovarian function via gut-ovary axis and lipid metabolism dysregulation. Show less
Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidenc Show more
Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG's preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG's action against KYD. Show less
Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in Show more
Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in this process. Through the automatization of the mapping ability, this area progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the VWFA and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions, suggesting that populations of neurons within the VWFA distinctively encode written and spoken language. This functional organization of neural populations enables the area to respond to both written and spoken inputs. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Show less
Quinolinic acid (QA) is a metabolite of tryptophan catabolism involved in the biosynthesis of nicotinamide adenine dinucleotide (NAD). It has been extensively studied in the context of neuropsychiatri Show more
Quinolinic acid (QA) is a metabolite of tryptophan catabolism involved in the biosynthesis of nicotinamide adenine dinucleotide (NAD). It has been extensively studied in the context of neuropsychiatric disorders in the past decades. Recent studies have also linked high plasma QA levels to obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes. In the present study, we have explored the impact of long-term oral QA administration on glucose and lipid metabolism in mice. We observed a protective role for QA in preventing hepatic lipid accumulation in high-fat-diet fed mice, whereas oral administration of NAD showed opposite effects. We further demonstrated that QA reduces hepatic lipid uptake by inhibiting the expression of lipoprotein lipase (LPL) and fatty acid translocase (CD36) in liver, thereby mitigating liver lipid accumulation in the context of a high-fat diet. Our data suggest that QA is an important regulator of lipid homeostasis and has potential as a therapeutic target for MASLD. Show less
<b>Introduction:</b> Colonic diverticular disease (diverticulosis) is a currently worldwide increasing gastrointestinal disorder with a particularly high prevalence in Western countries. T Show more
<b>Introduction:</b> Colonic diverticular disease (diverticulosis) is a currently worldwide increasing gastrointestinal disorder with a particularly high prevalence in Western countries. The operative treatment of acute diverticulitis could be executed through open or laparoscopic techniques. A non-resectional procedure, namely laparoscopic peritoneal lavage (LPL) and drainage, has also been adopted as a less invasive treatment strategy to treat patients with diverticular perforation and purulent peritonitis.<b>Aim:</b> The present work was conducted to pool the currently available evidence regarding the safety and efficacy of LPL for the treatment of complicated perforated diverticulitis.<b>Methods:</b> The analysis included studies that compared patients who underwent LPL to those who underwent surgical resection. Fifteen articles were eligible for this review after searching the Scopus, PubMed Central, Cochrane Library, and Google Scholar databases.<b>Results:</b> The meta-analysis demonstrated that operative time and blood loss were significantly lower in the LPL group (p<0.001). The rates of overall morbidity and reoperation were comparable in the two groups (p = 0.57 and 0.74, respectively). There were significantly lower rates of cardiovascular (p < 0.001) and respiratory complications (p = 0.01), incisional/parastomal hernia formation (p = 0.02), ICU admission (p < 0.001), length of hospital stay (p < 0.001), permanent stoma formation (p < 0.001), and mortality (p < 0.001), and higher rates of sepsis (p = 0.03), intra-abdominal abscess formation (p < 0.001), and postoperative recurrence (p < 0.001) in the LPL group.<b>Conclusions:</b> Compared to the colon resection procedures for the treatment of complicated diverticulitis, laparoscopic peritoneal lavage had comparable overall morbidity and reoperation rates and lower rates of permanent stoma formation and mortality. Still, there is concern regarding the recurrence and intra-abdominal abscess formation. Show less
The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epitheli Show more
The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epithelial cells are the precursors of milk fat globules (MFG). However, it is unclear what happens to proteins during the transformation process from LD to MFG, and little is known about the regulation of LD diameter in vivo. In this study, 12 mid-lactation Saanen dairy goats were randomly divided into 2 groups: a control group fed a basal diet and an experimental group fed a basal diet supplemented with CLA at 90 g/d. Goat milk was collected for analysis of composition and MFG size. Mammary gland tissue was collected for analysis of LD diameter and proteins. The size of MFG was found to depend on LD diameter in the mammary glands of dairy goats. The regression equations for MFG size (Y) and LD diameter (x) were Y Show less
Taurine is an amino acid widely present in animal tissues. Recent research has highlighted the importance of including taurine in the diet of various commercially relevant species. This study evaluate Show more
Taurine is an amino acid widely present in animal tissues. Recent research has highlighted the importance of including taurine in the diet of various commercially relevant species. This study evaluated the impact of taurine supplementation in the diet of Seriola rivoliana on the activity of antioxidant enzymes, lysozyme, and the expression of metabolic-related genes in different tissues. Three experimental diets were designed with 0% (Control), 1%, and 2% of taurine concentrations, administered over 60 days. The results indicated that taurine supplementation significantly improved the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) in the liver and plasma. Additionally, an increase in lysozyme (LZM) activity was observed in mucus and plasma of the fish. Regarding gene expression, the 2% taurine supplementation significantly increased the expression of critical genes involved in carbohydrates and lipid metabolism, such as glucokinase (gck), hexokinase (hk1), and acetyl-CoA carboxylase (acoa1) in the liver, as well as lipase (lpl), cholecystokinin (cck), and trypsin (try1) in the intestine. These results suggest that taurine not only enhances the antioxidant and immune capacity of the fish but also optimizes their energy metabolism and digestion, which could contribute to improved aquaculture diets, promoting more excellent resistance to oxidative stress and better overall health of fish raised under intensive conditions. Show less
Prediction has become a key concept for understanding language comprehension, language production, and more recently reading. Recent studies suggest that predictive mechanisms in reading may be relate Show more
Prediction has become a key concept for understanding language comprehension, language production, and more recently reading. Recent studies suggest that predictive mechanisms in reading may be related to domain-general statistical learning (SL) abilities that support the extraction of regularities from sequential input. Both mechanisms have been discussed in relation to developmental dyslexia. Some suggest that SL is impaired in dyslexia with negative effects on the ability to make linguistic predictions. Others suggest that dyslexic readers rely to a greater extent on semantic and syntactic predictions to compensate for lower-level deficits. Here, we followed these two research questions in a single study. We therefore assessed the effects of semantic and syntactic prediction in reading and SL abilities in a population of university students with dyslexia and a group of typical readers using fMRI. The SL task was a serial reaction time (SRT) task that was performed inside and outside the scanner. The predictive reading task was performed in the scanner and used predictive versus nonpredictive semantic and syntactic contexts. Our results revealed distinct neural networks underlying semantic and syntactic predictions in reading, group differences in predictive processing in the left precentral gyrus and right anterior insula, and an association between predictive reading and SL, particularly in dyslexic readers. These findings contribute to our understanding of the interplay between SL, predictive processing, and compensation in dyslexia, providing new insights into the neural mechanisms that support reading. Show less
Given that lipoprotein lipase (LPL) activity assays are not standardized for clinical use, we aimed to define reference values applicable to our clinical setting and identify a cut-off point to help d Show more
Given that lipoprotein lipase (LPL) activity assays are not standardized for clinical use, we aimed to define reference values applicable to our clinical setting and identify a cut-off point to help distinguish Familial Chylomicronemia Syndrome from Multifactorial Chylomicronemia Syndrome, particularly in patients with inconclusive genetic findings. We evaluated 28 patients with a history of TG levels above 880 mg/dL (10 mmol/L), and assessed their likelihood of FCS using the Moulin score. LPL activity was measured in post-heparin plasma using a radiometric assay. Thirty normotriglyceridemic controls were used to define reference values. Genetic testing for FCS canonical genes and lipid profile was performed in all sHTG patients. The reference value for LPL activity was 33.3 (18.7-70.3) mIU, with a cut-off of 8.42 mIU (25 % of the median of NTG) to distinguish FCS from MCS. Eighteen patients without genetic variants in canonical genes, a Moulin score <9 and LPL activity >25 % of NTG, were classified as MCS. Five genetic diagnosed FCS patients, with a Moulin score>10 presented LPL activity <25 % of NTG. Four patients with inconclusive genetic results and a Moulin score>10 were classified as FCS according to LPL activity. LPL activity in patients with sHTG could be useful for differentiating FCS and MCS, particularly in patients with ambiguous or negative genetic findings, highlighting the need for specialized laboratory support in diagnostics. Show less
Our use of language, which is profoundly social in nature, essentially takes place in interactive contexts and is shaped by precise coordination dynamics that interlocutors must observe. Thus, languag Show more
Our use of language, which is profoundly social in nature, essentially takes place in interactive contexts and is shaped by precise coordination dynamics that interlocutors must observe. Thus, language interaction is highly demanding on fast adjustment of speech production. Here, we developed a real-time coupled-oscillators virtual partner (VP) that allows - by changing the coupling strength parameters - to modulate the ability to synchronise speech with a virtual speaker. Then, we recorded the intracranial brain activity of 16 patients with drug-resistant epilepsy while they performed a verbal coordination task with the VP. More precisely, patients had to repeat short sentences synchronously with the VP. This synchronous speech task is efficient to highlight both the dorsal and ventral language pathways. Importantly, combining time-resolved verbal coordination and neural activity shows more spatially differentiated patterns and different types of neural sensitivity along the dorsal pathway. More precisely, high-frequency activity (HFa) in left secondary auditory regions is highly sensitive to verbal coordinative dynamics, while primary regions are not. Finally, while bilateral engagement was observed in the HFa of the inferior frontal gyrus BA44 - which seems to index online coordinative adjustments that are continuously required to compensate deviation from synchronisation - interpretation of right hemisphere involvement should be approached cautiously due to relatively sparse electrode coverage. These findings illustrate the possibility and value of using a fully dynamic, adaptive, and interactive language task to gather deeper understanding of the subtending neural dynamics involved in speech perception, production as well as their interaction. Show less
This study used whole-genome sequence data on 406 beef cattle (203 Hanwoo and 203 Angus) to detect signatures of selection using four different methods; integrated haplotype score (iHS), Rsb, XP-EHH, Show more
This study used whole-genome sequence data on 406 beef cattle (203 Hanwoo and 203 Angus) to detect signatures of selection using four different methods; integrated haplotype score (iHS), Rsb, XP-EHH, and runs of homozygosity (ROH). Based on Rsb and XP-EHH analysis, 36 and 21 genomic regions differed significantly between Angus and Hanwoo breeds. Within breeds, we identified 108 regions (76 in Hanwoo and 32 in Angus) with the ROH analysis and 331 regions with the iHS method (298 in Hanwoo and 33 in Angus). The candidate genes related to meat quality, such as HSPA9 and LPL, were found within Hanwoo, while genes associated with growth and meat quantity traits, including ACTC1 and TMEM68, were identified within Angus. This study can assist in understanding the selection history of these breeds and identifying the genomic regions associated with the traits selected for in the breeding programs for these cattle breeds. Show less
Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle pa Show more
Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm Show less