Isolation, whole genome sequencing and application of a broad-spectrum Salmonella phage.

Salmonella is considered as one of the most common zoonotic /foodborne pathogens in the world. The application of bacteriophages as novel antibacterial agents in food substrates has become an emerging strategy. Bacteriophages have the potential to control Salmonella contamination.We have isolated and characterized a broad-spectrum Salmonella phage, SP154, which can lyse 9 serotypes, including S. Enteritidis, S. Typhimurium, S. Pullorum, S. Arizonae, S. Dublin, S. Cholerasuis, S. Chester, S. 1, 4, [5], 12: i: -, and S. Derby, accounting for 81.9% of 144 isolates. SP154 showed a short latent period (40 min) and a high burst size (with the first rapid burst size at 107 PFUs/cell and the second rapid burst size at approximately 40 PFUs/cell). Furthermore, SP154 activity has higher survival rates across various environmental conditions, including pH 4.0-12.0 and temperatures ranging from 4 to 50 °C for 60 min, making it suitable for diverse food processing and storage applications. Significant reductions in live Salmonella were observed in different foods matrices such as milk and chicken meat, with a decrease of up to 1.9 log10 CFU/mL in milk contamination and a 1 log10 CFU/mL reduction in chicken meat. Whole genome sequencing analysis revealed that SP154 belongs to the genus Ithacavirus, subfamily Humphriesvirinae, within the family Schitoviridae. Phylogenetic analysis based on the terminase large subunit supported this classification, although an alternate tree using the tail spike protein gene suggested affiliation with the genus Kuttervirus, underscoring the limitations of relying on a single gene for phylogenetic inference. Importantly, no virulence or antibiotic resistance genes were detected in SP154. Our research highlights the potential of using SP154 for biocontrol of Salmonella in the food industry.

High Density 3D Carbon Tube Nanoarray Electrode Boosting the Capacitance of Filter Capacitor.

Electric double-layer capacitors (EDLCs) with fast frequency response are regarded as small-scale alternatives to the commercial bulky aluminum electrolytic capacitors. Creating carbon-based nanoarray electrodes with precise alignment and smooth ion channels is crucial for enhancing EDLCs' performance. However, controlling the density of macropore-dominated nanoarray electrodes poses challenges in boosting the capacitance of line-filtering EDLCs. Herein, a simple technique to finely adjust the vertical-pore diameter and inter-spacing in three-dimensional nanoporous anodic aluminum oxide (3D-AAO) template is achieved, and 3D compactly arranged carbon tube (3D-CACT) nanoarrays are created as electrodes for symmetrical EDLCs using nanoporous 3D-AAO template-assisted chemical vapor deposition of carbon. The 3D-CACT electrodes demonstrate a high surface area of 253.0 m2 g-1, a D/G band intensity ratio of 0.94, and a C/O atomic ratio of 8. As a result, the high-density 3D-CT nanoarray-based sandwich-type EDLCs demonstrate a record high specific areal capacitance of 3.23 mF cm-2 at 120 Hz and exceptional fast frequency response due to the vertically aligned and highly ordered nanoarray of closely packed CT units. The 3D-CT nanoarray electrode-based EDLCs could serve as line filters in integrated circuits, aiding power system miniaturization.

Research on the mechanism of leader-follower product sales competition based on market access restrictions and forward contract considerations.

Market access restrictions have been the focus of attention for various market players, but there are fewer studies on the competitive mechanism of market access restrictions on firms' product sales. This paper investigates the competitive mechanism of leader-follower product sales based on market access restrictions and forward contracts. First, the mechanism of leader-follower sales decisions based on market access restrictions and forward contracts is clarified. Second, it models the forward default risk suffered by followers and the profit rate of leader-follower based on market access restrictions and forward considerations by Bayes' posterior probability method. Moreover, it severely explores the impact mechanisms of the degree of market access restrictions on leaders and followers when followers do not adopt and adopt forwards and makes a simulation analysis. The results show that: (i) When followers do not employ forward contracts, the less restrictive degree of market access increases the supply of leaders, and leaders' competition for product sales further leads to a decrease in the provision of followers. (ii) When followers use forwards, leaders' and followers' expected discounted profit rates decrease with the total supply of products in the market increases. (iii) If the degree of market access restrictions is low, the followers suffer an increased forward default risk, resulting in their rate of revenue decrease. The findings of this paper have some practical significance and policy implications for the regulator to adjust the degree of market access restriction in each restricted access area, to establish a reasonable and efficient competitive environment for product sales, as well as for firms to choose the optimal way of competing for product sales.

Associations between hollow viscus injury and acute kidney injury in blunt abdominal trauma: A national trauma data bank analysis.

PURPOSE: It is well established that hollow viscus perforation leads to sepsis and acute kidney injury (AKI) in non-trauma patients. However, the relationship between traumatic hollow viscus injury (HVI) and AKI is not well understood. Utilizing data from the National Trauma Data Bank, we investigated whether HVI serves as a risk factor for AKI. Additionally, we examined the characteristics of AKI in stable patients who underwent conservative treatment. METHODS: We reviewed blunt abdominal trauma (BAT) cases from 2012 to 2015, comparing patients with and without AKI. Significant factors from univariate analysis were tested in a multivariate logistic regression (MLR) to identify independent AKI determinants. We also analyzed subsets: patients without HVI and stable patients given conservative management. RESULTS: Out of the 563,040 BAT patients analyzed, 9073 (1.6%) developed AKI. While a greater proportion of AKI patients had HVI than those without AKI (13.3% vs. 5.2%, p < 0.001), this difference wasn't statistically significant in the MLR (p = 0.125). Notably, the need for laparotomy (odds = 3.108, p < 0.001) and sepsis (odds = 13.220, p < 0.001) were identified as independent risk factors for AKI. For BAT patients managed conservatively (systolic blood pressure >90 mmHg, without HVI or laparotomy; N = 497,066), the presence of sepsis was a significant predictor for the development of AKI (odds = 16.914, p < 0.001). CONCLUSIONS: While HVI wasn't a significant risk factor for AKI in BAT patients, the need for laparotomy was. Stable BAT patients managed conservatively are still at risk for AKI due to non-peritonitis related sepsis.

Unexpected Self-Assembly of Nanographene Oxide Membranes upon Electron Beam Irradiation for Ultrafast Ion Sieving.

Nanographene oxide (nGO) flakes-graphene oxide with a lateral size of ≈100 nm or less-hold great promise for superior flux and energy-efficient nanofiltration membranes for desalination and precise ionic sieving owing to their unique high-density water channels with less tortuousness. However, their potential usage is currently limited by several challenges, including the tricky self-assembly of nano-sized flakes on substrates with micron-sized pores, severe swelling in aqueous solutions, and mechanical instability. Herein, the successful fabrication of a robust membrane stacked with nGO flakes on a substrate with a pore size of 0.22 µm by vacuum filtration is reported. This membrane achieved an unprecedented water permeance above 819.1 LMH bar-1, with a high rejection rate of 99.7% for multivalent metal ions. The nGO flakes prepared using an electron beam irradiation method, have uniquely pure hydroxyl groups and abundant aromatic regions. The calculations revealed the strong hydrogen bonds between two nGO flakes, which arise from hydroxyl groups, coupled with hydrophobic aromatic regions, greatly enhance the stability of stacked flakes in aqueous solutions and increase their effective lateral size. The research presents a simple yet effective approach toward the fabrication of advanced 2D nanographene membranes with superior performance for ion sieving applications.

Discovery and Development of NLRP3 Inhibitors Targeting the LRR Domain to Disrupt NLRP3-NEK7 Interaction for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Targeting NLRP3 inflammasome, specifically its interaction with NEK7 via the LRR domain of NLRP3, is a promising therapeutic strategy. Our research aimed to disrupt this interaction by focusing on the LRR domain. Through virtual screening, we identified five compounds with potent anti-inflammatory effects and ideal LRR binding affinity. Lead compound C878-1943 underwent structural optimization, yielding pyridoimidazole derivatives with different anti-inflammatory activities. Compound I-19 from the initial series effectively inhibited caspase-1 and IL-1ß release in an adjuvant-induced arthritis (AIA) rat model, significantly reducing joint swelling and spleen/thymus indices. To further enhance potency and extend in vivo half-life, a second series including II-8 was developed, demonstrating superior efficacy and longer half-life. Both I-19 and II-8 bind to the LRR domain, inhibiting NLRP3 inflammasome activation. These findings introduce novel small molecule inhibitors targeting the LRR domain of NLRP3 protein and disrupt NLRP3-NEK7 interaction, offering a novel approach for RA treatment.

d-Pinitol Improves Diabetic Sarcopenia by Regulation of the Gut Microbiome, Metabolome, and Proteome in STZ-Induced SAMP8 Mice.

d-Pinitol (DP) is primarily found in Vigna sinensis, which has been shown to have hypoglycemic and protective effects on target organs. However, the mechanism of DP in treating diabetic sarcopenia (DS) is still unclear. To explore the underlying mechanism of DS and the protective targets of DP by high-throughput analysis of 16S rRNA gene, metabolome, and the proteome. Streptozotocin-induced SAMP8 mice were intragastrically administrated DP (150 mg/kg) for 8 weeks. Fecal 16S rRNA gene sequencing and gastrocnemius muscle metabolomic and proteomic analyses were completed to investigate the gut-muscle axis interactions. DP significantly alleviated the muscle atrophy in diabetic mice. Dysfunction of the gut microbiota was observed in the DS mice. DP significantly reduced the Parabacteroides, Akkermansia, and Enterobacteriaceae, while it increased Lachnospiraceae_NK4A136. Metabolome and proteome revealed that 261 metabolites and 626 proteins were significantly changed in the gastrocnemius muscle of diabetic mice. Among these, DP treatment restored 44 metabolites and 17 proteins to normal levels. Functional signaling pathways of DP-treated diabetic mice included nucleotide metabolism, ß-alanine, histidine metabolism, ABC transporters, and the calcium signaling pathway. We systematically explored the molecular mechanism of DS and the protective effect of DP, providing new insights that may advance the treatment of sarcopenia.

Abnormal cerebral blood flow in children with developmental stuttering.

BACKGROUND: Stuttering affects approximately 5% of children; however, its neurological basis remains unclear. Identifying imaging biomarkers could aid in early detection. Accordingly, we investigated resting-state cerebral blood flow (CBF) in children with developmental stuttering. METHODS: Pulsed arterial spin labelling magnetic resonance imaging was utilised to quantify CBF in 35 children with developmental stuttering and 27 healthy controls. We compared normalised CBF between the two groups and evaluated the correlation between abnormal CBF and clinical indicators. RESULTS: Compared with healthy controls, the stuttering group exhibited decreased normalised CBF in the cerebellum lobule VI bilaterally, right cuneus, and left superior occipital gyrus and increased CBF in the right medial superior frontal gyrus, left rectus, and left dorsolateral superior frontal gyrus. Additionally, normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus was positively correlated with stuttering severity. CONCLUSIONS: Children who stutter display decreased normalised CBF primarily in the cerebellum and occipital gyrus, with increased normalised CBF in the frontal gyrus. Additionally, the abnormal CBF in the left cerebellum lobule VI and left superior occipital gyrus was associated with more severe symptoms, suggesting that decreased CBF in these areas may serve as a novel neuroimaging clue for stuttering. IMPACT: Stuttering occurs in 5% of children and often extends into adulthood, which may negatively affect quality of life. Early detection and treatment are essential. We used pulsed arterial spin labelling magnetic resonance imaging to visualise the resting-state cerebral blood flow (CBF) in children who stutter and healthy children. Normalised CBF was decreased in stutterers in the cerebellum and occipital gyrus and increased in the frontal gyrus. Stuttering severity was linked to abnormal normalised CBF in the left cerebellum lobule VI and left superior occipital gyrus, suggesting that CBF may serve as a novel neuroimaging clue for stuttering.

Diastereoselective Synthesis of 4-Hydroxy-2-quinolinones via Formal [2 + 4] Cycloaddition Reactions Using α-Diazo Pyrazoleamides as C2 Synthons.

A rhodium-catalyzed highly stereoselective formal [2 + 4]-cycloaddition reaction of α-diazo pyrazoleamides and 2-aminophenyl ketones that produces 4-hydroxy-2-quinolinones in good yields with excellent diastereoselectivities has been developed. A pyrazolium ylide species that is generated from α-diazo pyrazoleamides is used as a C2 synthon for this cycloaddition. This protocol offers an efficient approach to a variety of 4-hydroxy-2-quinolinones featuring sequential quaternary centers.

A non-antibiotic antimicrobial drug, a biological bacteriostatic agent, is useful for treating aerobic vaginitis, bacterial vaginosis, and vulvovaginal candidiasis.

Background: Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are widely used to treat vaginitis, recurrent vaginitis occurs in some patients. Resistance to these agents is the major cause of recurrent vaginitis. Therefore, there is an urgent need to develop novel drugs. Methods: We investigated the efficacy of a new biological bacteriostatic agent (BBA), composed of lysozyme, phytoalexin, chitosan oligosaccharide, sinensetin, 18ß/20α-glycyrrhizin, and betaine, against vaginitis using in vitro and in vivo studies. First, we evaluated the antibacterial effects of BBA against 13 microbial strains commonly present in aerobic vaginitis, bacterial vaginosis, vulvovaginal candidiasis, and healthy vaginas. Second, we assessed the safety of various doses of BBA administered orally for 4 weeks in female mice. Third, we examined the in vivo anti-proliferative and anti-inflammatory effects of BBA in Candida albicans-, Candida glabrata-, and Gardnerella-induced vaginitis models. Finally, we evaluated the anti-vaginitis effect of a BBA gel prepared with 0.5% (w/v) ammonium acryloyldimethyltaurate/Vp copolymer. Results: BBA effectively suppressed the growth of the main causative pathogens of vaginitis in vitro. BBA, either undiluted or diluted two-fold, inhibited all microorganisms cultured for 8 h. No obvious organ damage was detected when BBA was administered to mice. Both BBA alone and 70% BBA in a gel formulation effectively inhibited the proliferation of C. albicans, C. glabrata, and Gardnerella in vaginal lavage samples and alleviated tissue inflammation in mice with vaginitis. The 70% BBA gel performed better than BBA alone at treating vaginitis in mice infected with Gardnerella vaginalis. Conclusion: BBA alone and a 70% BBA gel inhibited the growth of pathogens and effectively alleviated inflammation caused by C. albicans, C. glabrata, and G. vaginalis.

Glassware Influences the Perception of Orange Juice in Simulated Naturalistic versus Urban Conditions.

The latest research demonstrates that people's perception of orange juice can be influenced by the shape/type of receptacle in which it happens to be served. Two studies are reported that were designed to investigate the impact, if any, that the shape/type of glass might exert over the perception of the contents, the emotions induced on tasting the juice and the consumer's intention to purchase orange juice. The same quantity of orange juice (100 ml) was presented and evaluated in three different glasses: a straight-sided, a curved and a tapered glass. Questionnaires were used to assess taste (aroma, flavour intensity, sweetness, freshness and fruitiness), pleasantness and intention to buy orange juice. Study 2 assessed the impact of the same three glasses in two digitally rendered atmospheric conditions (nature vs urban). In Study 1, the perceived sweetness and pleasantness of the orange juice was significantly influenced by the shape/type of the glass in which it was presented. Study 2 reported significant interactions between condition (nature vs urban) and glass shape (tapered, straight-sided and curved). Perceived aroma, flavour intensity and pleasantness were all significantly affected by the simulated audiovisual context or atmosphere. Compared to the urban condition, perceived aroma, freshness, fruitiness and pleasantness were rated significantly higher in the nature condition. On the other hand, flavour intensity and sweetness were rated significantly higher in the urban condition than in the natural condition. These results are likely to be relevant for those interested in providing food services, or company managers offering beverages to their customers.

Identification of candidate plasma miRNA biomarkers for the diagnosis of head and neck squamous cell carcinoma.

Aim: Current head and neck squamous cell carcinoma (HNSCC) diagnostic tools are limited, so this study aimed to identify diagnostic microRNA (miRNA) biomarkers from plasma. Materials & methods: A total of 76 HNSCC and 76 noncancerous control (NC) plasma samples underwent microarray analysis and quantitative reverse transcription PCR to screen for diagnostic plasma miRNAs. The diagnostic potential of the miRNAs was evaluated by the receiver operating characteristic curve. Results: miR-95-3p and miR-579-5p expression was shown to be significantly upregulated, and that of miR-1298-3p to be downregulated in HNSCC patients compared with controls. The final diagnostic panel included miR-95-3p, miR-579-5p and miR-1298-3p with an area under the curve of 0.83. Conclusion: This three-miRNA panel has potential for the diagnosis of HNSCC.

Early detection of head and neck cancer is crucial. In this study, we established a diagnostic model based on blood samples. This is a convenient diagnostic and screening tool that can help people early detect head and neck cancer.

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells.

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.

Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer.

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.

Effect of obstructive sleep apnea on postoperative delirium: a system review and meta-analysis.

PURPOSE: To investigate the impact of obstructive sleep apnea (OSA) on postoperative delirium (PD), and evaluate the effectiveness of positive airway pressure (PAP) therapy on PD among OSA patients. METHODS: We systematically searched Embase, Cochrane Library and PubMed databases from their establishment to November 27, 2022. A random-effects approach was employed to determine aggregated results. Subgroup and sensitivity analyses were carried out to investigate heterogeneity. RESULTS: Sixteen eligible studies were included in the analysis. Thirteen studies revealed that OSA significantly elevated the likelihood of developing PD (OR = 1.71; 95%CI = 1.17 to 2.49; p = 0.005). Subgroup analysis according to delirium assessment scales showed that OSA did not exhibit an association with the incidence of PD assessed by the Confusion Assessment Method-Intensive Care Unit (OR = 1.14; 95%CI = 0.77 to 1.67; p = 0.51) but enhanced the likelihood of developing PD evaluated with other measurement scales (OR = 2.15; 95%CI = 1.44 to 3.19; p = 0.0002). Three additional studies explored the impact of PAP treatment on PD among OSA individuals, indicating no significant reduction in PD incidence with PAP use (OR = 0.58; 95%CI = 0.13 to 2.47; p = 0.46). CONCLUSIONS: OSA may not be a risk factor for PD in critically ill patients in the intensive care unit, but may increase the likelihood of developing PD among individuals receiving regular care in the ward postoperatively. The efficacy of PAP therapy in decreasing PD incidence among OSA patients remains debatable.

Characteristics of JN.1-derived SARS-CoV-2 subvariants SLip, FLiRT, and KP.2 in neutralization escape, infectivity and membrane fusion.

SARS-CoV-2 variants derived from the immune evasive JN.1 are on the rise worldwide. Here, we investigated JN.1-derived subvariants SLip, FLiRT, and KP.2 for their ability to be neutralized by antibodies in bivalent-vaccinated human sera, XBB.1.5 monovalent-vaccinated hamster sera, sera from people infected during the BA.2.86/JN.1 wave, and class III monoclonal antibody (Mab) S309. We found that compared to parental JN.1, SLip and KP.2, and especially FLiRT, exhibit increased resistance to COVID-19 bivalent-vaccinated human sera and BA.2.86/JN.1-wave convalescent sera. Interestingly, antibodies in XBB.1.5 monovalent vaccinated hamster sera robustly neutralized FLiRT and KP.2 but had reduced efficiency for SLip. These JN.1 subvariants were resistant to neutralization by Mab S309. In addition, we investigated aspects of spike protein biology including infectivity, cell-cell fusion and processing, and found that these subvariants, especially SLip, had a decreased infectivity and membrane fusion relative to JN.1, correlating with decreased spike processing. Homology modeling revealed that L455S and F456L mutations in SLip reduced local hydrophobicity in the spike and hence its binding to ACE2. In contrast, the additional R346T mutation in FLiRT and KP.2 strengthened conformational support of the receptor-binding motif, thus counteracting the effects of L455S and F456L. These three mutations, alongside D339H, which is present in all JN.1 sublineages, alter the epitopes targeted by therapeutic Mabs, including class I and class III S309, explaining their reduced sensitivity to neutralization by sera and S309. Together, our findings provide insight into neutralization resistance of newly emerged JN.1 subvariants and suggest that future vaccine formulations should consider JN.1 spike as immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.

Association of UGT1A6 gene polymorphisms with sodium valproate-induced tremor in patients with epilepsy.

BACKGROUND: Individual susceptibility to sodium valproate (VPA)-induced tremors may be due to genetic polymorphisms in the gene encoding the uridine diphosphate glucuronosyltransferase (UGT) enzyme, which affec the drug's clinical efficacy and cause toxic side effects. This study aimed to investigate the association between UGT1A6 polymorphisms and VPA-induced tremors in patients with epilepsy. METHODS: In total, 128 patients with epilepsy were enrolled. Patients with epilepsy who received VPA were divided into tremor and non-tremor groups. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the genotype of UGT1A6 polymorphisms. RESULTS: Carriers of the UGT1A6 A541G mutant genotype conferred a higher risk of tremor than wild-type carriers (odds ratio 2.128, P = 0.045). Logistic regression analysis showed that the A541G mutant genotype was a significant genetic risk factor for VPA-induced tremors. This suggests that individual susceptibility to VPA-induced tremors may result, at least partially, from genetic variation in UGT1A6 A541G. CONCLUSIONS: Patients with epilepsy carrying the UGT1A6 A541G mutant genotype may have VPA-induced tremors, and early detection of this genotype will help guide the clinical individualizsation of VPA treatment.

Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.

Low glucose is a common microenvironment for rapidly growing solid tumors, which has developed multiple approaches to survive under glucose deprivation. However, the specific regulatory mechanism remains largely elusive. In this study, we demonstrate that glucose deprivation, while not amino acid or serum starvation, transactivates the expression of DCAF1. This enhances the K48-linked polyubiquitination and proteasome-dependent degradation of Rheb, inhibits mTORC1 activity, induces autophagy, and facilitates cancer cell survival under glucose deprivation conditions. This study identified DCAF1 as a new cellular glucose sensor and uncovered new insights into mechanism of DCAF1-mediated inactivation of Rheb-mTORC1 pathway for promoting cancer cell survival in response to glucose deprivation.

Prefrontal activity and heart rate variability during cognitive tasks may show different changes in young and older adults with and without mild cognitive impairment.

Background: Age-related decline in cognitive function is often linked to changed prefrontal cortex (PFC) activity and heart rate variability (HRV). Mild cognitive impairment (MCI), a transitional stage between normal aging and dementia, might have further degeneration beyond aging. This study aimed to investigate the differences between young and older adults with or without MCI in cognitive functions, task-induced PFC activation and HRV changes. Methods: Thirty-one healthy young adults (YA), 44 older adults (OA), and 28 older adults with MCI (OA-MCI) were enrolled and compared in this cross-sectional study. Each participant received a one-time assessment including cognitive and executive functions, as well as the simultaneous recording of PFC activity and HRV during a cognitive task paradigm. Results: We observed age-related decrease in global cognitive functions, executive functions, HRV, and increase in PFC activity. The MCI further deteriorated the global cognitive and executive performances, but not the HRV or the prefrontal activation. Conclusion: Older people showed lower performances in general cognitive function and executive function, compensatory increase of PFC activity, and reduced HRV. Older people with MCI had further deterioration in cognitive performance, but not in PFC activation and HRV.

High-resolution and highly-multiplexed option for fiber-fed spectrograph of the wide field MUltiplexed Survey Telescope (MUST).

In recent decades, rapid advances in astronomical imaging campaigns have generated an urgent need for detailed spectroscopic surveys with increased speed and efficiency. The 6.5 m MUltiplexed Survey Telescope (MUST) aims to address these current demands. The performance of the multi-object fiber-fed spectrograph (MOFS) plays a critical role for spectroscopic survey telescopes, directly influencing the realization of scientific aims. In this paper, we demonstrate a high-resolution and highly-multiplexed option for MOFS of MUST. The system is believed to be first to apply a 92 mm × 92 mm large-size detector in a Schmidt-like camera and reduces the average central obscuration to 14%. Thanks to the F/1.25 camera design with excellent image quality, the spectrograph achieves up to 800 150µm-large-core optical fibers integration. It can obtain the broadband spectral information (395 nm-435 nm, 520 nm-570 nm, 610 nm-680 nm) of 800 objects with a high resolution of >16,000 within one exposure. The spectrograph theory, design method, and final system scheme of the MOFS can offer good reference and guidance for the spectrograph design in the spectroscopic survey.