Integrated analysis of genes shared between type 2 diabetes mellitus and osteoporosis.

Background: The relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OP) has been widely recognized in recent years, but the mechanism of interaction remains unknown. The aim of this study was to investigate the genetic features and signaling pathways that are shared between T2DM and OP. Methods: We analyzed the GSE76894 and GSE76895 datasets for T2DM and GSE56815 and GSE7429 for OP from the Gene Expression Omnibus (GEO) database to identify shared genes in T2DM and OP, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). Shared genes were then further analyzed for functional pathway enrichment. We selected the best common biomarkers using the least absolute shrinkage and selection operator (LASSO) algorithm and validated the common biomarkers, followed by RT-PCR, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to validate the expression of these hub genes in T2DM and OP mouse models and patients. Results: We found 8,506 and 2,030 DEGs in T2DM and OP, respectively. Four modules were identified as significant for T2DM and OP using WGCNA. A total of 19 genes overlapped with the strongest positive and negative modules of T2DM and OP. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed these genes may be involved in pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin system signaling pathway. The LASSO algorithm calculates the six optimal common biomarkers. RT-PCR results show that LTB, TPBG, and VNN1 were upregulated in T2DM and OP. Immunofluorescence and Western blot show that VNN1 is upregulated in the pancreas and bones of T2DM model mice and osteoporosis model mice. Similarly, the level of VNN1 in the sera of patients with T2DM, OP, and T2DM and OP was higher than that in the healthy group. Conclusion: Based on the WGCNA and LASSO algorithms, we identified genes and pathways that were shared between T2DM and OP. Both pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin systems may be associated with the pathogenesis of T2DM and OP. Moreover, VNN1 may be a potential diagnostic marker for patients with T2DM complicated by OP. This study provides a new perspective for the systematic study of possible mechanisms of combined OP and T2DM.

Childhood exposure to organophosphate pesticides: Functional connectivity and working memory in adolescents.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents. METHODS: We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance. RESULTS: We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males. CONCLUSION: In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.

Longitudinal changes in functional neural activation and sensitization during face processing in fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we previously demonstrated aberrant neural activity responding to faces in young girls with FXS cross-sectionally. Here, we tested the hypothesis that abnormalities in neural activation and sensitization would increase with age in 65 girls with FXS, ages 5-16 years, relative to an age-matched control group of 52 girls who had comparable cognitive function and clinical symptoms. METHODS: Functional NIRS data were collected at two time points, 2.8±0.6 years apart during a face-processing task. Linear mixed-effects models examined longitudinal neural profiles in girls with FXS and control. Correlational analysis was performed to examine associations between neural sensitization (increasing neural response to repeated stimuli), and clinical ratings. RESULTS: In girls with FXS, 32 participants had one, and 24 had two fNIRS scans. In controls, 21 had one, and 29 had two fNIRS scans. Brain activations in the right middle and superior frontal gyri were higher in FXS than controls at both time points. Neural sensitization also increased in FXS at a higher rate than controls in the superior frontal gyrus when responding to upright faces. For the FXS group, sensitization in the superior frontal gyrus positively correlated with longitudinal increases in anxiety and social avoidance scores. CONCLUSION: Girls with FXS show increasingly abnormal neural activation and sensitization responding to faces over time. Aberrant neural sensitization in girls with FXS is associated with longitudinal changes in anxiety and social skills.

Enantioselective synthesis of 4-aryl-3,4-dihydrocoumarins via N-heterocyclic carbene catalyzed ß-arylation/cyclization of α-bromoenals.

4-Aryl-3,4-dihydrocoumarins are one of the most important structural motifs. Herein, we disclose an enantioselective N-heterocyclic carbene catalyzed ß-arylation/cyclization of α-bromoenals with 3-aminophenols under mild conditions. The protocol allows for the rapid preparation of 4-aryl-3,4-dihydrocoumarins in acceptable yields with good enantioselectivities. The products of this reaction could be converted into chiral diarylpropanoic acid derivatives without erosion of the enantioselectivity.

Action Programmed Nanoantibiotics with pH-Induced Collapse and Negative-Charged-Surface-Induced Deformation against Antibiotic-Resistant Bacterial Peritonitis.

The incorporation of well-designed antibiotic nanocarriers, along with an antibiotic adjuvant effect, in combination with various antibiotics, offers an opportunity to combat drug-resistant strains. However, precise control over morphology and encapsulated payload release can significantly impact their antibacterial efficacy and synergistic effects when used alongside antibiotics. Here, this study focuses on developing lipopeptide-based nanoantibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH-induced collapse and negative-charged-surface-induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug-resistant strains. The modulation regulations of the lipopeptide nanocarriers with modular design are governed by the authors. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip results in a significantly low fractional inhibitory concentration index of 0.375 and a remarkable reduction in the minimum inhibitory concentration of Cip against multidrug-resistant (MDR) Escherichia coli (clinical isolated strains) by up to 32-fold. The survival rate of MDR E. coli peritonitis treated with nanoantibiotics is significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic shows no obvious toxicity to major organs.

Genomic analysis of PIN-FORMED genes reveals the roles of SmPIN3 in root architecture development in Salvia miltiorrhiza.

Salvia miltiorrhiza is a widely utilized medicinal herb in China. Its roots serve as crucial raw materials for multiple drugs. The root morphology is essential for the quality of this herb, but little is known about the molecular mechanism underlying the root development in S. miltiorrhiza. Previous study reveals that the polar auxin transport is critical for lateral root development in S. miltiorrhiza. Whether the auxin efflux carriers PIN-FORMEDs (PINs) are involved in this process is worthy investigation. In this study, we identified nine SmPIN genes in S. miltiorrhiza, and their chromosome localization, physico-chemical properties, and phylogenetic relationship were analyzed. SmPINs were unevenly distributed across four chromosomes, and a variety of hormone responsive elements were detected in their promoter regions. The SmPIN proteins were divided into three branches according to the phylogenetic relationship. SmPINs with close evolutionary distance showed similar conserved motif features. The nine SmPINs showed distinct tissue-specific expression patterns and most of them were auxin-inducible genes. We generated SmPIN3 overexpression S. miltiorrhiza seedlings to investigate the function of SmPIN3 in the root development in this species. The results demonstrated that SmPIN3 regulated the root morphogenesis of S. miltiorrhiza by simultaneously affecting the lateral root development and the root anatomical structure. The root morphology, patterns of root xylem and phloem as well as the expressions of genes in the auxin signaling pathway all altered in the SmPIN3 overexpression lines. Our findings provide new insights for elucidating the regulatory roles of SmPINs in the auxin-mediated root development in S. miltiorrhiza.

Association between preoperative albumin and length of hospital stay in non-cardiac surgery patients with pulmonary hypertension: A secondary retrospective analysis.

To explore the risk factors affecting the length of hospital stay (LOS) as well as to examine the relationship between preoperative serum albumin levels and LOS following non-cardiac, non-obstetric surgery in patients with pulmonary hypertension (PHTN). This study represents a secondary retrospective analysis based on 287 non-cardiac, non-obstetric procedures performed on 195 PTHN patients at a single institution in the USA between 2007 and 2013. The primary outcome was the LOS. We conducted a multiple logistic regression analysis to compare the LOS between the 2 groups, divided at a serum albumin level of 3.5 g/dL. After adjusting for multiple covariates, the ORs for the long length of stay (LOS > 7 days) for the high group(albumin > 3.5 g/dL) compared with the low group (albumin ≤ 3.5 g/dL) were 0.35 (95%CI: 0.21~0.6), 0.41 (95%CI: 0.22 ~0.76), 0.41 (95%CI: 0.18~0.94) from model 2 to model 4. The stratified analysis results indicate that these findings are stable (p for trend > 0.05). In this study, it was observed that low levels of preoperative albumin were associated with an increased risk of prolonged hospital stay after non-cardiac, non-obstetric surgery in patients with PHTN. This implies that optimizing preoperative nutrition could potentially reduce the LOS for non-cardiac, non-obstetric surgery in patients with PHTN.

Enhancement of Colorimetric pH-Sensitive Film Incorporating Amomum tsao-ko Essential Oil as Antibacterial for Mantis Shrimp Spoilage Tracking and Fresh-Keeping.

Anthocyanin-based smart packaging has been widely used for food freshness monitoring, but it cannot meet the requirements of smart films with antibacterial properties. This study aimed to enhance the antibacterial properties of intelligent films by incorporating Amomum tsao-ko essential oil (AEO) for mantis shrimp spoilage tracking and keeping the product fresh. A smart film was designed by introducing AEO and purple potato anthocyanin (PPA) to a polyvinyl alcohol/cellulose nanocrystal (PVA/CNC) polymer matrix. Our findings revealed that APP and AEO imparted the smart film with a favorable oxygen barrier, UV protection, mechanical properties, and antioxidant and pH/NH3-sensitive functions. Interestingly, the PVA/CNC-AEO-PPA film achieved 45.41% and 48.25% bactericidal efficacy against S. putrefaciens and V. parahaemolyticus, respectively. Furthermore, a visual observation confirmed that the target film (PVA/CNC-AEO-PPA) changed color significantly during mantis shrimp spoilage: rose red-light red-pink-light gray-dark gray. Meanwhile, the PVA/CNC-AEO-PPA film retarded the quality deterioration of the mantis shrimp effectively. The PVA/CNC-AEO-PPA film shows great application potential in mantis shrimp preservation and freshness monitoring; it is expected to become a rapid sensor for detecting seafood quality non-destructively and a multifunctional film for better preservation of product quality.

Small Intestinal Endocrine Cell Derived Exosomal ACE2 Protects Islet ß-Cell Function by Inhibiting the Activation of NLRP3 Inflammasome and Reducing ß-Cell Pyroptosis.

Background: The "gut-islets axis" is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets ß-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the "gut-islet axis.". Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets ß cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2. Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by ß-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets ß-cell function and ß-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces ß-cell pyroptosis. Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and ß cell pyroptosis, thereby restoring islets ß cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.

Genome-wide identification of the SAUR gene family and screening for SmSAURs involved in root development in Salvia miltiorrhiza.

KEY MESSAGE: SmSAUR4, SmSAUR18, SmSAUR28, SmSAUR37, and SmSAUR38 were probably involved in the auxin-mediated root development in Salvia miltiorrhiza. Salvia miltiorrhiza is a widely utilized medicinal plant in China. Its roots and rhizomes are the main medicinal portions and are closely related to the quality of this herb. Previous studies have revealed that auxin plays pivotal roles in S. miltiorrhiza root development. Whether small auxin-up RNA genes (SAURs), which are crucial early auxin response genes, are involved in auxin-mediated root development in S. miltiorrhiza is worthy of investigation. In this study, 55 SmSAUR genes in S. miltiorrhiza were identified, and their physical and chemical properties, gene structure, cis-acting elements, and evolutionary relationships were analyzed. The expression levels of SmSAUR genes in different organs of S. miltiorrhiza were detected using RNA-seq combined with qRT‒PCR. The root development of S. miltiorrhiza seedlings was altered by the application of indole-3-acetic acid (IAA), and Pearson correlation coefficient analysis was conducted to screen SmSAURs that potentially participate in this physiological process. The diameter of primary lateral roots was positively correlated with SmSAUR4. The secondary lateral root number was positively correlated with SmSAUR18 and negatively correlated with SmSAUR4. The root length showed a positive correlation with SmSAUR28 and SmSAUR37 and a negative correlation with SmSAUR38. The fresh root biomass exhibited a positive correlation with SmSAUR38 and a negative correlation with SmSAUR28. The aforementioned SmSAURs were likely involved in auxin-mediated root development in S. miltiorrhiza. Our study provides a comprehensive overview of SmSAURs and provides the groundwork for elucidating the molecular mechanism underlying root morphogenesis in this species.

[Effects and Mechanisms of Polystyrene Microplastics on Extracellular Antibiotic Resistance Genes in Wastewater].

Microplastics (MPs) and antibiotic resistance genes (ARGs) are typical co-existing emerging pollutants in wastewater treatment plants. MPs have been shown to alter the distribution pattern of ARGs in sludge, but their effects on free extracellular ARGs (feARGs) in wastewater remain unclear. In this study, we used fluorescence quantitative PCR to investigate the dynamics of feARGs (including tetC, tetO, sul1, and sul2) in wastewater and their transition mechanisms after 60 d of exposure to typical MPs (polystyrene, PS). The results showed that the absolute abundance of tetracycline feARGs decreased by 28.4 %-76.0 % and 35.2 %-96.2 %, respectively, under nm-level and mm-level PS exposure and changed by -55.4 %-122.4 % under µm-level PS exposure. The abundance of sul1 showed a trend of nm-level > µm-level > mm-level upon PS exposure, and the changes in sul1 abundance was greater with ρ(PS)=50 mg·L-1 exposure. The relative abundance of sul2 was reduced by 25.4 %-42.6 % and 46.1 %-90.3 % after µm-level and mm-level PS exposure, respectively, and increased by 1.9-3.9 times after nm-level PS exposure, and the sul2 showed a higher reduction at ρ (PS)=50 mg·L-1 exposure than that at ρ (PS)=0.5 mg·L-1. The Pearson correlation analysis showed that the relative abundance of feARGs during PS exposure was positively correlated with cell membrane permeability and typical mobile genetic elements (intI1) abundance and negatively correlated with reactive oxygen species level. Our findings elucidated the effects and corresponding mechanisms of PS on the growth and mobility of feARGs in wastewater, providing a scientific basis for the control of the combined MPs and ARGs pollution in wastewater.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and MSNs@PDA nanoparticles for miRNA amplified detection and fluorescence imaging.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and mesoporous silica nanoparticles@polydopamine (MSNs@PDA) was established to detect miRNA. The surface of MSNs rich in mesopores was coated with a layer of PDA, which can adsorb and quench the fluorescence of single-stranded Fuel DNA with fluorescent carbon dots (CDs) modified at the end through fluorescence resonance energy transfer (FRET). After adding double-stranded DNA-gold nanoparticles (dsDNA-AuNPs) and target let-7a, it will trigger two toehold-mediated strand displacement reactions (TSDR), leading to the recovery of fluorescence and the recycling of target let-7a (excitation wavelength: 380 nm; emission wavelength: 458 nm). The recovery value of fluorescence is proportional to the logarithm of the target microRNA let-7a concentration, thus realizing the sensitivity amplification detection of disease markers. The MSNs@PDA@Fuel DNA-CDs/dsDNA-AuNPs nanoplatform based on the strategy of "on-off-on" and TSDR cyclic amplification may hold great potential as an effective and safe nanoprobe for accurate fluorescence imaging of diseases related to miRNA with low abundances.

AZIN2 is associated with apoptosis of germ cells in undescended testis.

Undescended testis (UDT), known as cryptorchidism (CRY), is a common congenital disorder in which one or both testicles do not descend normally into the scrotum. A unilateral UDT model was established by inducing UDT in mice through surgery. The results showed that the testis in the UDT model group was abnormal; the lumen of the seminiferous tubule was atrophic; apoptosis, necrosis and shedding were observed in many of the germ cells; the level of sex hormones was abnormal; and mature sperm was reduced. Subsequently, transcriptome sequencing was conducted on the testicular tissue of UDT model mice. Through analysis and verification of differential genes, AZIN2 was identified as playing a key role in the decline in male fertility caused by cryptorchidism. AZIN2 expression and spermine content was down-regulated in the testis of the UDT group. We then used a combination of hypoxanthine and xanthine to create a GC-1 cell damage model. In this model, AZIN2 expression and spermine content was down-regulated. When si-Azin2 transfected GC-1 cells, cell viability and proliferation were decreased. However, in the GC-1 cell damage model transfected with Azin2 over-expressed plasmid, AZIN2 expression and spermine content was up-regulated, reversing the cell damage caused by hypoxanthine and xanthine, and restoring the proliferation ability of GC-1 cells. These results indicate that in UDT, down-regulated AZIN2 expression is a factor in testicular damage. This discussion of the connection between AZIN2 and germ cells has important clinical significance as it provides an important reference for the diagnosis and treatment of cryptorchidism.

PEG-crosslinked O-carboxymethyl chitosan films with degradability and antibacterial activity for food packaging.

This study developed a kind of PEG-crosslinked O-carboxymethyl chitosan (O-CMC-PEG) with various PEG content for food packaging. The crosslinking agent of isocyanate-terminated PEG was firstly synthesized by a simple condensation reaction between PEG and excess diisocyanate, then the crosslink between O-carboxymethyl chitosan (O-CMC) and crosslinking agent occurred under mild conditions to produce O-CMC-PEG with a crosslinked structure linked by urea bonds. FT-IR and 1H NMR techniques were utilized to confirm the chemical structures of the crosslinking agent and O-CMC-PEGs. Extensive research was conducted to investigate the impact of the PEG content (or crosslinking degree) on the physicochemical characteristics of the casted O-CMC-PEG films. The results illuminated that crosslinking and components compatibility could improve their tensile features and water vapor barrier performance, while high PEG content played the inverse effects due to the microphase separation between PEG and O-CMC segments. The in vitro degradation rate and water sensitivity primarily depended on the crosslinking degree in comparison with the PEG content. Furthermore, caused by the remaining -NH2 groups of O-CMC, the films demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. When the PEG content was 6% (medium crosslinking degree), the prepared O-CMC-PEG-6% film possessed optimal tensile features, high water resistance, appropriate degradation rate, low water vapor transmission rate and fine broad-spectrum antibacterial capacity, manifesting a great potential for application in food packaging to extend the shelf life.

Characterization of a predictive signature for tumor microenvironment and immunotherapy response in hepatocellular carcinoma involving neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

[Correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy].

OBJECTIVE: To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). METHODS: Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children's Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. RESULTS: Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c.677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group (P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. CONCLUSION: The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Biofilm of petroleum-based and bio-based microplastics in seawater in response to Zn(II): Biofilm formation, community structure, and microbial function.

Microplastic biofilms are novel vectors for the transport and spread of pathogenic and drug-resistant bacteria. With the increasing use of bio-based plastics, there is an urgent need to investigate the microbial colonization characteristics of these materials in seawater, particularly in comparison with conventional petroleum-based plastics. Furthermore, the effect of co-occurring contaminants, such as heavy metals, on the formation of microplastic biofilms and bacterial communities remains unclear. In this study, we compared the biofilm bacterial community structure of petroleum-based polyethylene (PE) and bio-based polylactic acid (PLA) in seawater under the influence of zinc ions (Zn2+). Our findings indicate that the biofilm on PLA microplastics in the late stage was impeded by the formation of a mildly acidic microenvironment resulting from the hydrolysis of the ester group on PLA. The PE surface had higher bacterial abundance and diversity, with a more intricate symbiotic pattern. The bacterial structures on the two types of microplastics were different; PE was more conducive to the colonization of anaerobic bacteria, whereas PLA was more favorable for the colonization of aerobic and acid-tolerant species. Furthermore, Zn increased the proportion of the dominant genera that could utilize microplastics as a carbon source, such as Alcanivorax and Nitratireductor. PLA had a greater propensity to harbor and disseminate pathogenic and drug-resistant bacteria, and Zn promoted the enrichment and spread of harmful bacteria such as, Pseudomonas and Clostridioides. Therefore, further research is essential to fully understand the potential environmental effects of bio-based microplastics and the role of heavy metals in the dynamics of bacterial colonization.

Design of battery shell stamping parameters for vehicles based on fusion of various artificial neural network models.

The application of neural network model in engineering prediction is frequent. The BPE shell material was optimized, and the reliability of the new material was verified by modal simulation. The accuracy of finite element modeling was ensured by constrained mode experiments, and all variables were preprocessed by Latin hypercube sampling. The design parameters were determined by Monte Carlo simulation. Four different neural networks, including back propagation (BP), radial basis function (RBF), extreme learning machine (ELM) and wavelet neural network (WNN), are used to train and learn the dataset. The BPE weight reduction ratio was 14.3%, the stress was reduced by 18.6%, deformation displacement was reduced by 14.2%, and the first-order mode was increased by 29.1%.

Comparison of genes involved in brain development: insights into the organization and evolution of the telencephalic pallium.

The mechanisms underlying the organization and evolution of the telencephalic pallium are not yet clear.. To address this issue, we first performed comparative analysis of genes critical for the development of the pallium (Emx1/2 and Pax6) and subpallium (Dlx2 and Nkx1/2) among 500 vertebrate species. We found that these genes have no obvious variations in chromosomal duplication/loss, gene locus synteny or Darwinian selection. However, there is an additional fragment of approximately 20 amino acids in mammalian Emx1 and a poly-(Ala)6-7 in Emx2. Lentiviruses expressing mouse or chick Emx2 (m-Emx2 or c-Emx2 Lv) were injected into the ventricle of the chick telencephalon at embryonic Day 3 (E3), and the embryos were allowed to develop to E12-14 or to posthatchling. After transfection with m-Emx2 Lv, the cells expressing Reelin, Vimentin or GABA increased, and neurogenesis of calbindin cells changed towards the mammalian inside-out pattern in the dorsal pallium and mesopallium. In addition, a behavior test for posthatched chicks indicated that the passive avoidance ratio increased significantly. The study suggests that the acquisition of an additional fragment in mammalian Emx2 is associated with the organization and evolution of the mammalian pallium.