[A study of mismatched negative in normal hearing patients of different ages].

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） µV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） µV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） µV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） µV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.

STUB1 exacerbates calcium oxalate-induced kidney injury by modulating reactive oxygen species-mediated cellular autophagy via regulating CFTR ubiquitination.

The formation of calcium oxalate (CaOx) crystals in the kidneys leads to renal epithelial damage and the progression of crystalline nephropathy. This study investigated the role of STIP1 homology and U-box protein 1 (STUB1), an E3 ubiquitin ligase, and cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, in CaOx-related renal damage and autophagy regulation. HK-2 cells were treated with various doses of CaOx monohydrate (COM) to simulate kidney injury in vitro. Cell viability, reactive oxygen species (ROS) production, and apoptosis were assessed. The regulation of CFTR ubiquitination by STUB1 was confirmed by immunoprecipitation. An in vivo model was established by injecting mice with glyoxylate. COM treatment dose-dependently decreased cell viability, increased TNF-α and ROS production, and induced apoptotic cell death in HK-2 cells. COM-treated cells also showed decreased CFTR protein expression. CFTR overexpression improved cell viability and reduced ROS production in COM-stimulated HK-2 cells. Bioinformatics analysis predicted CFTR's ubiquitination binding site for STUB1. Further analysis confirmed the role of STUB1 as a ubiquitin ligase in CFTR degradation. Knockdown of STUB1 upregulated CFTR expression, while STUB1 overexpression had the opposite effect. Knockdown of CFTR reversed the impact of STUB1 deficiency on autophagy. The in vivo experiments showed that CFTR overexpression attenuated kidney tissue damage and CaOx deposition in mice. STUB1-mediated CFTR ubiquitination plays a crucial role in mitigating calcium oxalate-related renal damage by regulating autophagy. Targeting the STUB1/CFTR axis may hold therapeutic potential for treating kidney injury associated with calcium oxalate deposition.

Evaluating the impact of recombinant human epidermal growth factor on scar formation in oral and maxillofacial traumatic wound healing.

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.

Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Drug delivery system based on metal-organic framework improved 5-Fluorouracil against spring viremia of carp virus.

Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo. The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC50) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.

SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity.

It has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how nsp15 processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research has mainly focused on short single-stranded RNA as substrates, and whether nsp15 prefers single-stranded or double-stranded RNA for cleavage is controversial. In the present work, we prepared numerous RNA substrates, including both long substrates mimicking the viral genome and short defined RNA, to clarify the substrate preference and cleavage pattern of SARS-CoV-2 nsp15. We demonstrated that SARS-CoV-2 nsp15 preferentially cleaved pyrimidine nucleotides located in less thermodynamically stable areas in dsRNA, such as AU-rich areas and mismatch-containing areas, in a nicking manner. Because coronavirus genomes generally have a high AU content, our work supported the mechanism that coronaviruses evade the antiviral response mediated by host cell dsRNA sensors by using nsp15 dsRNA nickase to directly cleave dsRNA intermediates formed during genome replication and transcription.

APOBEC shapes tumor evolution and age at onset of lung cancer in smokers.

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues1,2. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B)3-6. However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low (LAS) and high (HAS) APOBEC mutagenesis. LAS are enriched for A3B-like mutagenesis and KRAS mutations, whereas HAS for A3A-like mutagenesis and TP53 mutations. Unlike APOBEC3A, APOBEC3B expression is strongly associated with an upregulation of the base excision repair pathway. Hypermutation by unrepaired A3A and tobacco smoking mutagenesis combined with TP53-induced genomic instability can trigger senescence7, apoptosis8, and cell regeneration9, as indicated by high expression of pulmonary healing signaling pathway, stemness markers and distal cell-of-origin in HAS. The expected association of tobacco smoking variables (e.g., time to first cigarette) with genomic/epigenomic changes are not observed in HAS, a plausible consequence of frequent cell senescence or apoptosis. HAS have more neoantigens, slower clonal expansion, and older age at onset compared to LAS, particularly in heavy smokers, consistent with high proportions of newly generated, unmutated cells and frequent immuno-editing. These findings show how heterogeneity in mutational burden across co-occurring mutational processes and cell types contributes to tumor development, with important clinical implications.

MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

Genome-wide identification and stress response analysis of BcaCPK gene family in amphidiploid Brassica carinata.

BACKGROUND: Calcium-dependent protein kinases (CPKs) are crucial for recognizing and transmitting Ca2+ signals in plant cells, playing a vital role in growth, development, and stress response. This study aimed to identify and detect the potential roles of the CPK gene family in the amphidiploid Brassica carinata (BBCC, 2n = 34) using bioinformatics methods. RESULTS: Based on the published genomic information of B. carinata, a total of 123 CPK genes were identified, comprising 70 CPK genes on the B subgenome and 53 on the C subgenome. To further investigate the homologous evolutionary relationship between B. carinata and other plants, the phylogenetic tree was constructed using CPKs in B. carinata and Arabidopsis thaliana. The phylogenetic analysis classified 123 family members into four subfamilies, where gene members within the same subfamily exhibited similar conserved motifs. Each BcaCPK member possesses a core protein kinase domain and four EF-hand domains. Most of the BcaCPK genes contain 5 to 8 introns, and these 123 BcaCPK genes are unevenly distributed across 17 chromosomes. Among these BcaCPK genes, 120 replicated gene pairs were found, whereas only 8 genes were tandem duplication, suggesting that dispersed duplication mainly drove the family amplification. The results of the Ka/Ks analysis indicated that the CPK gene family of B. carinata was primarily underwent purification selection in evolutionary selection. The promoter region of most BcaCPK genes contained various stress-related cis-acting elements. qRT-PCR analysis of 12 selected CPK genes conducted under cadmium and salt stress at various points revealed distinct expression patterns among different family members in response to different stresses. Specifically, the expression levels of BcaCPK2.B01a, BcaCPK16.B02b, and BcaCPK26.B02 were down-regulated under both stresses, whereas the expression levels of other members were significantly up-regulated under at least one stress. CONCLUSION: This study systematically identified the BcaCPK gene family in B. carinata, which contributes to a better understanding the CPK genes in this species. The findings also serve as a reference for analyzing stress responses, particularly in relation to cadmium and salt stress in B. carinata.

Effects of Preoperative Oral Carbohydrate on Perioperative Maternal Outcomes Undergoing Cesarean Section: A Systematic Review and Meta-Analysis.

Purpose: Preoperative oral carbohydrate (CHO) is a rapid postoperative rehabilitation protocol that improves perioperative outcomes and is widely used in adult surgical patients. However, pregnant women are excluded because of the possibility of aspiration due to delayed gastric emptying. This meta-analysis was conducted to evaluate the efficacy of preoperative oral CHO in elective cesarean section. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 2023. Randomized controlled trials were included. The risk of bias was assessed using the Cochrane tool. Risk ratios and 95% confidence intervals were calculated. Meta-analysis was performed using random-effects models to estimate risk ratios and mean differences (MDs) with 95% confidence intervals (CIs). The outcomes included thirst and hunger scores, incidence of vomiting and nausea, time to flatus, and homeostatic model assessment of insulin resistance (HOMA-IR). Results: A total of nine studies with 1211 patients were included in the analysis. The levels of thirst and hunger were evaluated using a 10-point visual analog scale, with 0 representing the best and 10 representing the worst. The severity of hunger (weighted mean difference (WMD: -2.34, 95% CI: -3.13 to -1.54), time to flatus (WMD: -3.51 hours, 95% CI: -6.85 to -0.17), and HOMA-IR (WMD: -1.04, 95% CI: -1.31 to -0.77) were significantly lower in the CHO group compared to the control group. However, there were no significant differences in the severity of thirst or the incidence of vomiting and nausea between the CHO and control groups. Conclusion: Preoperative oral CHO during cesarean section alleviates thirst and hunger, shortens the time of postoperative flatus, and reduces HOMA-IR. However, the available evidence is insufficient to reach a clear consensus on the benefits or harms of preoperative oral CHO during cesarean section. Therefore, it is premature to make a definitive recommendation for or against its routine use.

Identification, Evolutionary Dynamics, and Gene Expression Patterns of the ACP Gene Family in Responding to Salt Stress in Brassica Genus.

Acyl carrier proteins (ACPs) have been reported to play a crucial role in responding to biotic and abiotic stresses, regulating growth and development. However, the biological function of the ACP gene family in the Brassica genus has been limited until now. In this study, we conducted a comprehensive analysis and identified a total of 120 ACP genes across six species in the Brassica genus. Among these, there were 27, 26, and 30 ACP genes in the allotetraploid B. napus, B. juncea, and B. carinata, respectively, and 14, 13, and 10 ACP genes in the diploid B. rapa, B. oleracea, and B. nigra, respectively. These ACP genes were further classified into six subclades, each containing conserved motifs and domains. Interestingly, the majority of ACP genes exhibited high conservation among the six species, suggesting that the genome evolution and polyploidization processes had relatively minor effects on the ACP gene family. The duplication modes of the six Brassica species were diverse, and the expansion of most ACPs in Brassica occurred primarily through dispersed duplication (DSD) events. Furthermore, most of the ACP genes were under purifying selection during the process of evolution. Subcellular localization experiments demonstrated that ACP genes in Brassica species are localized in chloroplasts and mitochondria. Cis-acting element analysis revealed that most of the ACP genes were associated with various abiotic stresses. Additionally, RNA-seq data revealed differential expression levels of BnaACP genes across various tissues in B. napus, with particularly high expression in seeds and buds. qRT-PCR analysis further indicated that BnaACP genes play a significant role in salt stress tolerance. These findings provide a comprehensive understanding of ACP genes in Brassica plants and will facilitate further functional analysis of these genes.

Risk relationship between inflammatory bowel disease and urolithiasis: A two-sample Mendelian randomization study.

BACKGROUND: The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs). METHODS: A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians. RESULTS: Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71]. CONCLUSION: A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

Osteogenesis or Apoptosis-Twofold Effects of Zn2+ on Bone Marrow Mesenchymal Stem Cells: An In Vitro and In Vivo Study.

Zinc (Zn) is a bioabsorbable metal that shows great potential as an implant material for orthopedic applications. Suitable concentrations of zinc ions promote osteogenesis, while excess zinc ions cause apoptosis. As a result, the conflicting impacts of Zn2+ concentration on osteogenesis could prove to be significant problems for the creation of novel materials. This study thoroughly examined the cell viability, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) cultured in various concentrations of Zn2+ in vitro and validated the osteogenesis effects of zinc implantation in vivo. The effective promotion of cell survival, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell (BMSCs) may be achieved at a low concentration of Zn2+ (125 µM). The excessively high concentration of zinc ions (>250 µM) not only reduces BMSCs' viability and proliferation but also causes them to suffer apoptosis due to the disturbed zinc homeostasis and excessive Zn2+. Moreover, transcriptome sequencing was used to examine the underlying mechanisms of zinc-induced osteogenic differentiation with particular attention paid to the PI3K-AKT and TGF-ß pathways. The present investigation elucidated the dual impacts of Zn2+ microenvironments on the osteogenic characteristics of rBMSCs and the associated processes and might offer significant insights for refining the blueprint for zinc-based biomaterials.

Comparison of the physical stability, microstructure and protein-lipid co-oxidation of O/W emulsions stabilized by l-arginine/l-lysine-modified soy protein hydrolysate.

This work investigated the physical stability, microstructure, and oxidative stability of the emulsions prepared by soy protein hydrolysate (SPH) after modification with different concentrations of l-arginine and l-lysine. l-Arginine and l-lysine significantly increased the absolute zeta potential values, and decreased droplet sizes of the emulsions, thereby improving the physical stability of the emulsions. Meanwhile, l-arginine and l-lysine markedly decreased the apparent viscosity of the emulsions. The measurement of interfacial protein adsorption percentage showed that l-arginine (≤0.5 %) promoted the adsorption of SPH at the oil-water interface, whereas l-lysine (≤1%) reduced the adsorption of SPH at the oil-water interface. In addition, l-arginine and l-lysine (≤0.5 %) could retard lipid and protein oxidation. Correlation analysis indicated that the improvement in the physical stability of the emulsions by l-arginine and l-lysine also enhanced the oxidative stability of the emulsions. In summary, l-arginine and l-lysine could be effective modifiers for the protein-based emulsion systems.

Diagnostic value of Video Electroencephalography combined with Magnetic Resonance Imaging-diffusion tensor imaging in epilepsy.

Objective: To explore the diagnostic value of video electroencephalography (VEEG) combined with magnetic resonance imaging diffusion tensor imaging (MRI-DTI) in epilepsy. Methods: In this retrospective observational study, clinical data of 60 patients who underwent both VEEG and MRI examinations at the Neurosurgery Department of Quzhou People's Hospital from December 2020 to March 2023 were retrospectively reviewed, and a total of 55 patients were finally included. We evaluated the diagnostic value of combining VEEG and MRI to determine seizure type, location of epileptic focus, and structural abnormalities of brain tissue, using surgical and pathological results as the gold standard. Results: The accuracy of the combined approach for determining the seizure type was 98.18%, which was higher than the accuracy of MRI (85.45%, P<0.05) or VEEG (81.82%, P<0.05) alone. The accuracy of joint examination for lesion location was 100.00%, which was higher than those of MRI (85.45%, P<0.05) or VEEG (83.64%, P<0.05) alone. Similar abnormal brain tissue structure detection rates was found for both MRI and VEEG (P>0.05). Conclusions: The application of MRI-DTI combined with VEEG to diagnose patients with epilepsy allows for the identification of abnormal structural changes in brain and the location of lesions. Combining both approaches can improve the diagnostic accuracy of each technique alone and provide a reference for the formulation and adjustment of disease management plans.

Mannose modified targeted immersion vaccine delivery system improves protective immunity against Infectious spleen and kidney necrosis virus in mandarin fish (Siniperca chuatsi).

Vaccination is an effective method to prevent viral diseases. However, the biological barrier prevents the immersion vaccine from achieving the best effect without adding adjuvants and carriers. Researches on the targeted presentation technology of vaccines with nanocarriers are helpful to develop immersion vaccines for fish that can break through biological barriers and play an effective role in fish defense. In our study, functionally modified single-walled carbon nanotubes (SWCNTs) were used as carriers to construct a targeted immersion vaccine (SWCNTs-M-MCP) with mannose modified major capsid protein (MCP) to target antigen-presenting cells (APCs), against iridovirus diseases. After bath immunization, our results showed that SWCNTs-M-MCP induced the presentation process and uptake of APCs, triggering a powerful immune response. Moreover, the highest relative percent survival (RPS) was 81.3% in SWCNTs-M-MCP group, which was only 41.5% in SWCNTs-MCP group. Altogether, this study indicates that the SWCNTs-based targeted immersion vaccine induces strong immune response and provided an effective protection against iridovirus diseases.

Outdoor fine particulate matter exposure and telomere length in humans: A systematic review and meta-analysis.

Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 µg/m3 increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (ß) of -0.12 (95% CI: -0.20, -0.03, I2= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I2= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.

CXCL13/CXCR5 promote chronic postsurgical pain and astrocyte activation in rats by targeting NLRP3.

Chronic postsurgical pain (CPSP) with high incidence negatively impacts the quality of life. X-C motif chemokine 13 (CXCL13) has been associated with postsurgery inflammation and exacerbates neuropathic pain in patients with CPSP. This study was aimed to illustrate the relationship between CXCL13 and nod-like receptor protein-3 (NLRP3), which is also involved in CPSP. A CPSP model was constructed by skin/muscle incision and retraction (SMIR) in right medial thigh, and the rats were divided into three groups: Sham, SMIR, and SMIR + anti-CXCL13 (intrathecally injected with anti-CXCL13 antibody). Then, the paw withdrawal threshold (PWT) score of rats was recorded. Primary rat astrocytes were isolated and treated with recombinant protein CXCL13 with or without NLRP3 inhibitor INF39. The expressions of CXCL13, CXCR5, IL-1ß, IL-18, GFAP, NLRP3, and Caspase-1 p20 were detected by real-time quantitative reverse transcription PCR, western blot, ELISA, immunocytochemistry, and immunofluorescence analyses. The anti-CXCL13 antibody alleviated SMIR-induced decreased PWT and increased expression of GFAP, CXCL13, CXCR5, NLRP3, and Caspase-1 p20 in spinal cord tissues. The production of IL-1ß, IL-18, and expression of CXCL13, CXCR5, GFAP, NLRP3, and Caspase-1 p20 were increased in recombinant protein CXCL13-treated primary rat astrocytes in a dose-dependent manner. Treatment with NLRP3 inhibitor INF39 inhibited the function of recombinant protein CXCL13 in primary rat astrocytes. The CXCL13/CXCR5 signaling could promote neuropathic pain, astrocytes activation, and NLRP3 inflammasome activation in CPSP model rats by targeting NLRP3. NLRP3 may be a potential target for the management of CPSP.

Structures and activation mechanism of the Gabija anti-phage system.

Prokaryotes have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB8. GajA functions as a DNA endonuclease that is inactive in the presence of ATP9. Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation.