Discussion on the relationship between gut microbiota and glioma through Mendelian randomization test based on the brain gut axis.

BACKGROUND: In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR). METHOD: We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis. RESULTS: Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk. CONCLUSION: This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.

Production and characterization of novel monoclonal antibodies against pathological human TDP-43 proteins.

The RNA/DNA-binding protein TDP-43 plays a pivotal role in the ubiquitinated inclusions characteristic of TDP-43 proteinopathies, including most cases of frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer disease (AD). To understand the mechanisms of pathological TDP-43 processing and identify potential biomarkers, we generated novel phosphorylation-independent monoclonal antibodies (MAbs) using bacteria-expressed human full-length recombinant TDP-43. Remarkably, we identified a distinctive MAb, No. 9, targeting an epitope in amino acid (aa) region 311-360 of the C-terminus. This antibody showed preferential reactivity for pathological TDP-43 inclusions, with only mild reactivity for normal nuclear TDP-43. MAb No. 9 revealed more pathology in FTLD-TDP type A and type B brains and in AD brains compared to the commercial p409/410 MAb. Using synthetic phosphorylated peptides, we also obtained MAbs targeting the p409/410 epitope. Interestingly, MAb No. 14 was found to reveal additional pathology in AD compared to the commercial p409/410 MAb, specifically, TDP-43-immunopositive deposits with amyloid plaques in AD brains. These unique immunopositivities observed with MAbs No. 9 and No. 14 are likely attributed to their conformation-dependent binding to TDP-43 inclusions. We expect that this novel set of MAbs will prove valuable as tools for future patient-oriented investigations into TDP-43 proteinopathies.

The Microstructure and Mechanical Properties of Si3N4f/BN/SiBCN Microcomposites Fabricated by the PIP Process.

SiBCN ceramics based on SiC, BN and Si3N4 structures have good comprehensive properties such as high-temperature resistance, oxidation resistance, creep resistance and long life, which makes it one of the very promising ceramic material systems in military and aerospace fields, etc. In this study, SiBCN ceramics, as well as Si3N4f/BN/SiBCN microcomposites, were prepared by a polymer infiltration pyrolysis method using PBSZ as the polymer precursor. The PBSZ was completely ceramized by pyrolysis at 900 °C. The weight loss and elemental bonding forms of the products after the pyrolysis of the precursors hardly changed from 600 °C to 900 °C. After pyrolysis at 600 °C for 4 h and using the BN coating obtained from twice deposition as the interfacial phase, a more desirable weak interface of fiber/matrix with a binding strength of 21.96 ± 2.01 MPa can be obtained. Si3N4f/BN/SiBCN ceramic matrix microcomposites prepared under the same pyrolysis conditions have a relatively good tensile strength of 111.10 MPa while retaining a weak interface between the fibers and the matrix. The results of the study provide more theoretical and methodological support for the application of new composite structural ceramic material systems.

Epidemiological survey and risk factor analysis of high-risk human papillomavirus in women in Longgang District, Shenzhen.

Objective: The objective of this study was to assess the prevalence of high-risk HPV infection in married women in Longgang District, Shenzhen, and to analyze the distribution of HPV subtypes across different age groups while identifying risk factors associated with HPV infection. Methods: 1. From January 2018 to December 2020, 209,627 married women in Longgang District were selected as study subjects, using high-risk HPV testing as the primary screening means. HPV 16 or 18 positive directly referred to colposcopy, other types positive continued liquid-based thin-layer cytology (TCT) examination, if ≥ ASCUS, referred to colposcopy, and biopsy if necessary. 2. 210 female patients who came to our hospital for HPV testing from January 2018 to December 2020 were used for the study, including 130 HPV-positive patients and 80 HPV-negative patients. The risk factors of HPV infection were studied by questionnaire. Results: The HPV infection rate in 2018 was 13.17%, including LSIL 6.87%, HSIL 3.57%, the single type infection rate was 79.83%, top5 monotypes were 52, 53, 16, 58, 81, multiple types infection rate was 20.17%, top5 multiple types were 52/ 53, 52/68, 16/52 52/58, 52/81; 2019 HPV positivity rate was 10.23%, including LSIL 5.98%, HSIL 5.81%, the monotypic infection rate was 82.5%, top5 monotypic were: 52, 16, 58, 51, 53, multi heavy sex infection rate was 17.5%, top5 multi typic were: 52/53, 52/58, 52/68, 16/52, 51/52; HPV positive rate in 2020 was 11.28%, including LSIL 6 %, HSIL 4.84%, monotypic infection rate was 79.89%, top5 monotypic were: 52, 16, 53, 58, 51, multiheavy category infection rate was 20.11%, top5 multitypic were: 52/58, 16/52, 52/68, 52/53, 51/52. 30-50 years old is the high prevalence age of HPV susceptibility, followed by 50-60 years old, and HPV52 is the most common type. 2. 210 female patients were surveyed by filling out questionnaires: Smoking history, age at first sex, age at first pregnancy, abortion, number of sexual partners, contraceptive method, bleeding during intercourse, cervicitis, vaginitis, sleeping habits, and mental status totaling 11 factors were significant between infected and control (P < .05). Dichotomous logistic regression analysis with these 11 factors as independent variables and HPV infection as dependent variable revealed that abortion (OR=2.117, 95% CI: 1.337-3.354), number of sexual partners (OR=2.562, 95% CI: 1.222-5.373), cervicitis (OR=2.873, 95% CI: 1.407-5.868), vaginitis (OR=2.413, 95% CI: 1.158-5.026) staying up late (OR=2.408, 95% CI: 1.134-5.115) and mental status (OR=3.139, 95% CI: 1.470-6.703) were six factors that were risk factors for HPV infection. Conclusion: The common HPV infection types among women in Longgang district were mainly 52, 16, 58, 53, and 51, with a predominance of a single type of infection. The positive rate and pathogenicity of HPV 52 were higher than HPV 16. Women aged 30-60 years should be included in priority screening for cervical lesions. The six factors of miscarriage, number of sexual partners, cervicitis, vaginitis, staying up late, and mental status were risk factors for HPV infection occurrence.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Ammonium Ion-Pre-Intercalated MnO2 on Carbon Cloth for High-Energy Density Asymmetric Supercapacitors.

With the continuous development of green energy, society is increasingly demanding advanced energy storage devices. Manganese-based asymmetric supercapacitors (ASCs) can deliver high energy density while possessing high power density. However, the structural instability hampers the wider application of manganese dioxide in ASCs. A novel MnO2-based electrode material was designed in this study. We synthesized a MnO2/carbon cloth electrode, CC@NMO, with NH4+ ion pre-intercalation through a one-step hydrothermal method. The pre-intercalation of NH4+ stabilizes the MnO2 interlayer structure, expanding the electrode stable working potential window to 0-1.1 V and achieving a remarkable mass specific capacitance of 181.4 F g-1. Furthermore, the ASC device fabricated using the CC@NMO electrode and activated carbon electrode exhibits excellent electrochemical properties. The CC@NMO//AC achieves a high energy density of 63.49 Wh kg-1 and a power density of 949.8 W kg-1. Even after cycling 10,000 times at 10 A g-1, the device retains 81.2% of its capacitance. This work sheds new light on manganese dioxide-based asymmetric supercapacitors and represents a significant contribution for future research on them.

Mechanism of salidroside regulating autophagy based on network pharmacology and molecular docking.

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.

Hypermethylation in the promoter regions of flavonoid pathway genes is associated with skin color fading during 'Daihong' apple fruit development.

Apple fruit skin color fading is not well understood although the molecular mechanism of skin color formation is well known. The red-fleshed apple cultivar 'Daihong' (DH) exhibited fading skin color during fruit development despite having a heterozygous R6 allele but lacking Red-TE for red fruit skin. In this study, transcriptomic analysis revealed the expression level of MdMYB10 increased with fruit development whereas reduced expression levels of MdMYBPA1, MdCHS, MdANS, MdUFGT, MdLAR, and MdANR were observed, consistent with decreased levels of chalcone, anthocyanin, catechin, epicatechin, and procyanidin B2. Whole-genome bisulfite sequencing (WGBS) indicated a global gain in cytosine methylation levels and increased methylation in 5' and 3' flanking regions of genes and transposable elements (TEs), and in TE bodies in all CG, CHG and CHH contexts, especially the mCHH context, during fruit development. The increased DNA methylation was attributed to reduced expression levels of DNA demethylase genes, including MdDME1, MdROS1, and MdROS2. Association analysis revealed a significant negative correlation between promoter methylation levels of MdCHS, MdCHI, MdMYBPA1, and their respective transcript levels, as well as a negative correlation between promoter methylation levels of MdCHS, MdCHI, MdANR, and MdFLS, and the content of chalcones, naringenin-7-glucoside, epicatechin, and quercetin. Treatment with the DNA demethylation agent 5-aza-2'-deoxycytidine verified the negative correlation between DNA methylation and gene expression within the flavonoid pathway. These findings suggest that hypermethylation in promoter regions of genes of the flavonoid biosynthesis pathway is associated with the reduction of gene expression and flavonoid content, and fruit skin color fading during DH apple development.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

Peripheral artery disease mediating the effect of metabolic syndrome related diseases on lower limb ulcers: Mendelian randomization analysis.

Background: Previous observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored. Method: This research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD. Results: Univariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD. Conclusion: Hypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.

Short-term exposure to extreme temperature and outpatient visits for respiratory diseases among children in the northern city of China: a time-series study.

BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Kiwifruit Peel Extract Improves the Alterations in Lipid Metabolism in High-fat Diet-fed Model Rats.

Previous studies have demonstrated that the kiwifruit peel, which is usually discarded by consumers and factories, has the highest polyphenol content among all parts of the kiwifruit. To maximize the utilization of these waste resources, the aim of this study was to examine the regulatory effects of polyphenols extracted from kiwifruit peel (KPE) on lipid metabolism and investigate their underlying mechanisms. Thirty-two male Sprague‒Dawley rats were divided into four groups: those fed a normal diet, those fed a high-fat (HF) diet, and those fed a HF diet with a low dose of KPE solution (50 mg/kg) or a high dose of KPE (100 mg/kg) by gavage. The findings of the study revealed that KPE effectively reduced body weight gain and the increases in triglycerides and total cholesterol in serum induced by the HF diet (HFD). Additionally, KPE supplementation led to a significant decrease in hepatic fat accumulation, potentially by increasing hepatic oxidation abilities. Hepatic lipidomics demonstrated that KPE influenced various metabolic pathways, including linoleic acid metabolism, steroid biosynthesis, and the biosynthesis of unsaturated fatty acids in HFD-induced rats, which were associated with the downregulation of FATP2, ACC, FAS, GPAT, DGTA1, DGTA2, and PPARγ expression as well as the upregulation of AMPK, PGC-1α, CPT-1, and PPARα expression. These findings suggest that KPE has considerable regulatory effects in rats with dyslipidaemia, which may provide supporting information for the reuse of kiwifruit peel.

Effect of chlorogenic acid grafted chitosan on microbiological compositions of sea bass (Lateolabrax japonicus) fillets: Dominant spoilage bacteria, inhibition activity and membrane damage mechanisms.

This study investigated the effect of chlorogenic acid grafted chitosan (CS-g-CA) on the microbiota composition of sea bass (Lateolabrax japonicus), isolated and identified the specific spoilage organisms (SSOs) in the late stage of refrigerated fillets and evaluation of their spoilage potential. Moreover, antibacterial activity and membrane damage mechanism of CS-g-CA against spoilage bacteria was also investigated. Illumina-MiSeq high throughput sequencing results showed that CS-g-CA retarded the growth of Pseudomonas spp., which largely contributed to delaying the quality degradation of sea bass during storage. Then nine spoilage bacteria were isolated and identified from the fillets at the end of storage and inoculated into sterile fish fillets to determine their spoilage capacity. Results showed that fish fillets inoculated with spoilage bacteria exhibited a significant increase in TVB-N, TBA and putrescine content and decreased sensory quality during storage. Subsequently, the inhibitory activity of CS-g-CA against spoilage bacteria was investigated and strains that were more sensitive to the CS-g-CA with a strong spoilage capacity were selected for the study of the inhibition mechanism. Results suggested that CS-g-CA had strong inhibitory activity and led to bacterial death through the mechanism of membrane damage. Overall, this study analyzed the effect of CS-g-CA on the preservation of fish fillets from a microbiological point of view to provide a reference for the anti-bacterial preservation of aquatic products.

Immunotherapy-Induced Hypophysitis Following Treatment With Tislelizumab in an Elderly Patient With Bladder Cancer and Prostate Cancer: A Case Report.

Immune checkpoint inhibitors represent a hopeful and emerging group of medications employed in the regulation of the immune response against cancer, displaying tremendous potential in cancer treatment. However, the administration of these drugs has been linked to the occurrence of adverse events, among which hypophysitis appears to be a prevailing complication affecting a substantial number of patients. Given the potential gravity of this condition, it is strongly recommended to actively monitor hormone levels throughout the treatment process, allowing for the prompt detection and provision of appropriate therapeutic measures. The present study showcases a case involving a 72-year-old individual afflicted with both bladder cancer and prostate cancer, who subsequently developed autoimmune hypophysitis and secondary adrenocortical insufficiency following the administration of programmed death protein 1 (PD-1) inhibitors.

An Accurate Electro-Thermal Coupling Model of a GaAs HBT Device under Floating Heat Source Disturbances.

Taking into consideration the inaccurate temperature predictions in traditional thermal models of power devices, we undertook a study on the temperature rise characteristics of heterojunction bipolar transistors (HBTs) with a two-dimensional cross-sectional structure including a sub-collector region. We developed a current-adjusted polynomial electro-thermal coupling model based on investigating floating heat sources. This model was developed using precise simulation data acquired from SILVACO (Santa Clara, CA, USA). Additionally, we utilized COMSOL software (version 5.6) to simulate the temperature distribution within parallel power cells, examining further impacts resulting from thermal coupling. The research findings indicate that the rise in current induces modifications in the local carrier concentration, thereby prompting variations in the local electric field, including changes in the heat source's peak location and intensity. The device's peak temperature exhibits a non-linear trend regulated by the current, revealing an error margin of less than 1.5% in the proposed current-corrected model. At higher current levels, the drift of the heat source leads to an increase in the heat dissipation path and reduces the coupling strength between parallel devices. Experiments were performed on 64 GaAs (gallium arsenide) HBT-based power cells using a QFI infrared imaging system. Compared to the traditional temperature calculation model, the proposed model increased the accuracy by 6.84%, allowing for more precise predictions of transistor peak temperatures in high-power applications.

The effects of double gelatin containing chitosan nanoparticles-calcium alginate coatings on the stability of chicken breast meat.

The effects of gelatin coatings (2% and 4%) containing chitosan nanoparticles (ChNPs; 1% and 2%), in combination with calcium-alginate coatings (CA; 2%), on quality attributes and shelf life of chicken breast meat were evaluated at 4°C for 12 days. The results indicated that double-active gelatin-calcium alginate coatings had significant (p < .05) effects on moisture and protein content. Incorporation of ChNPs into double gelatin-CA coatings led to significant reduction (p < .05) in TBARS, pH, and TVB-N values at the end of storage. The counts of total viable count (TVC), coliforms, yeasts, and molds were significantly (p < .05) lower in all coated samples, particularly in treated samples by 4% gelatin containing 2% ChNPs + 2% CA coatings (6.85, 6.78, and 5.91 log CFU/g, respectively, compared with 8.35, 8.76, and 7.71 log CFU/g in control) at the end of keeping time. The results of sensory attributes showed that the coated samples had higher overall acceptability scores compared with the untreated samples. A synergistic relationship between the concentrations of gelatin and ChNPs was observed in maintaining the quality characteristics of meat samples during storage. Therefore, this study aims to evaluate the performance of double gelatin coating containing ChNPs in combination with CA coating in the storage quality improvement of chicken breast meat stored for 12 days at 4 °C to develop novel and practical coatings for meat and meat products.

miRNA-137-5p improves spatial memory and cognition in Alzheimer's mice by targeting ubiquitin-specific peptidase 30.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder causing progressive dementia. Research suggests that microRNAs (miRNAs) could serve as biomarkers and therapeutic targets for AD. Reduced levels of miR-137 have been observed in the brains of AD patients, but its specific role and downstream mechanisms remain unclear. This study sought to examine the therapeutic potential of miR-137-5p agomir in alleviating cognitive dysfunction induced in AD models and explore its potential mechanisms. METHODS: This study utilized bioinformatic analysis and a dual-luciferase reporter assay to investigate the relationship between miR-137-5p and ubiquitin-specific peptidase 30 (USP30). In vitro experiments were conducted using SH-SY5Y cells to assess the impact of miR-137-5p on Aß1-42 neurotoxicity. In vivo experiments on AD mice evaluated the effects of miR-137-5p on cognition, Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis, as well as its influence on USP30 levels. RESULTS: It was discovered that miR-137-5p mimics efficiently counteract Aß1-42 neurotoxicity in SH-SY5Y cells, a protective effect that is negated by USP30 overexpression. In vivo experiments demonstrated that miR-137-5p enhances the cognition and mobility of AD mice, significantly reducing Aß1-42 deposition, Tau hyperphosphorylation, and neuronal apoptosis within the hippocampus and cortex regions. Mechanistically, miR-137-5p significantly suppresses USP30 levels in mice, though USP30 overexpression partially buffers against miR-137-5p-induced AD symptom improvement. CONCLUSION: Our study proposes that miR-137-5p, by instigating the downregulation of USP30, has the potential to act as a novel and promising therapeutic target for AD.

Glycerol-weighted chemical exchange saturation transfer nanoprobes allow 19F/1H dual-modality magnetic resonance imaging-guided cancer radiotherapy.

Recently, radiotherapy (RT) has entered a new realm of precision cancer therapy with the introduction of magnetic resonance (MR) imaging guided radiotherapy systems into the clinic. Nonetheless, identifying an optimized radiotherapy time window (ORTW) is still critical for the best therapeutic efficacy of RT. Here we describe pH and O2 dual-sensitive, perfluorooctylbromide (PFOB)-based and glycerol-weighted chemical exchange saturation transfer (CEST) nano-molecular imaging probes (Gly-PFOBs) with dual fluorine and hydrogen proton based CEST MR imaging properties (19F/1H-CEST). Oxygenated Gly-PFOBs ameliorate tumor hypoxia and improve O2-dependent radiotherapy. Moreover, the pH and O2 dual-sensitive properties of Gly-PFOBs could be quantitatively, spatially, and temporally monitored by 19F/1H-CEST imaging to optimize ORTW. In this study, we describe the CEST signal characteristics exhibited by the glycerol components of Gly-PFOBs. The pH and O2 dual-sensitive Gly-PFOBs with19F/1H-CEST MR dual-modality imaging properties, with superior therapeutic efficacy and biosafety, are employed for sensitive imaging-guided lung cancer RT, illustrating the potential of multi-functional imaging to noninvasively monitor and enhance RT-integrated effectiveness.

Feeding Behavior Responses of the Small Copepod, Paracalanus parvus, to Toxic Algae at Different Concentrations.

The feeding relationship between copepods and phytoplankton has immense ecological significance. This study investigated the feeding behavior of copepods by studying the feeding selectivity of Paracalanus parvus, a key small copepod species, using a high-speed camera. The feeding behavior of P. parvus separately fed on three algae, Prorocentrum minimum, Alexandrium minutum, and Thalassiosira weissflogii, was studied at five different concentrations. The factors characterizing feeding behavior, including the beating frequency (BF), beating time (BT), and rejection behavior, were analyzed. The average BT and BF of P. parvus fed on toxic algae were significantly lower than those of copepods fed on nontoxic algae, indicating that the toxic algae negatively affected their feeding behavior. There were no significant differences in feed rejection among the three algae during the short period of experimentation, indicating that the rejection behavior was insignificant in the early period (within 20 min) of feeding on toxic algae. The feeding behavior was inhibited when the concentration reached 250 cells/mL. The BT was initially affected at increasing concentrations followed by the BF, and P. minimum and A. minutum reduced the BF at concentrations of 250 and 1000 cells/mL, respectively. Analysis of the average BFs revealed that P. parvus was more significantly affected by P. minimum containing diarrheal shellfish poison than by A. minutum containing paralytic shellfish poison. The BF of copepods fed on P. minimum was significantly lower than that of copepods fed on A. minutum at 250-500 cells/mL but was not significantly different from that at 1000 cells/mL. This indicated that the inhibitory effect of P. minimum on the feeding behavior was more significant at concentrations observed at the onset of red tide blooms (0.25-0.5 × 102 cells/mL), but insignificant at concentrations reaching those in advanced red tides (>103 cells/mL). This study demonstrates that toxic dinoflagellates alter the feeding behavior of copepods and describes the variations in their feeding response to different algal species and concentrations. The findings provide crucial insights for further studies on the feeding relationship between copepods and phytoplankton and on functional assessment of plankton ecosystems.