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Abstract Alzheimer's disease is the predominant form of dementia, and disulfidptosis is the latest reported mode of cell death that impacts various disease processes. This study used bioinformatics to analyze genes associated with disulfidptosis in Alzheimer's disease comprehensively. Based on the public datasets, the differentially expressed genes associated with disulfidptosis were identified, and immune cell infiltration was investigated through correlation analysis. Subsequently, hub genes were determined by a randomforest model. A prediction model was constructed using logistic regression. In addition, the drug-target affinity was predicted by a graph neural network model, and the results were validated by molecular docking. Five hub genes (PPEF1, NEUROD6, VIP, NUPR1, and GEM) were identified. The gene set showed significant enrichment for AD-related pathways. The logistic regression model demonstrated an AUC of 0.952, with AUC values of 0.916 and 0.864 in validated datasets. The immune infiltration analysis revealed significant heterogeneity between the Alzheimer's disease and control groups. High-affinity drugs for hub genes were identified. Through our study, a disease prediction model was constructed using potential biomarkers, and drugs targeting the genes were predicted. These results contribute to further understanding of the molecular mechanisms underlying Alzheimer's disease.

Abstract Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

ABSTRACT: The objective of this study was to evaluate the effects of different levels of glycerol monolaurate (GML) on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens. A total of 480 Hy-Line Variety Brown hens (age 54 wk) were randomly assigned to 5 treatments: the control group (basal diet) and 4 GML groups (basal diet supplemented with 100, 200, 300, and 400 mg/kg GML). Each treatment consisted of 8 replicates with 12 hens each and the trial lasted for 8 wk. The results showed that dietary inclusion of GML increased the ADFI in the entire experimental period and the average egg weight in wk 5 to 8 and wk 1 to 8 of the experiment (linear, P < 0.05). Dietary GML addition linearly increased albumen height, Haugh unit and yolk color, and quadratically increased eggshell thickness (P < 0.05). The serum SOD activity, T-AOC and IgG concentrations in the 200 mg/kg GML group, and GSH-Px activity in 200 and 300 mg/kg GML groups were increased, while the MDA concentration in 200 and 300 mg/kg GML groups was decreased than those in the control group (P < 0.05). The jejunal villus height and villus height: crypt depth in 300 mg/kg GML group were higher than that in the control group (P < 0.05). The mRNA expression of TLR4, IL-1β and TNF-α in spleen and jejunum decreased with the increase of dietary GML concentration (linear, P < 0.05). In conclusion, dietary GML supplementation could improve egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens, and dietary 300 mg/kg GML inclusion is suggested.

The progress of deep learning technology has made image classification an important application field. Image style classification is a complex task involving the recognition of the whole picture, including the recognition of salient features and detailed features. This study is based on the ResNet algorithm and has improved its Resnet 50 version with excellent performance. In the model architecture, we introduce blur pool operation and replace the traditional Relu function with Celu activation function. In addition, the triplet attention mechanism was integrated to further enhance the model performance. Through a series of experiments, it is found that the improved ResNet50 model has the highest classification accuracy of 80.6% on large-scale image data sets, which is 11.7% higher than the traditional ResNet50 model. In terms of recognition of similar style images, the model incorporating triplet attention demonstrated higher average accuracy (74%) and recall (82%). This improvement has achieved certain results and has certain technical reference value for various styles of image classification fields.

Objective. This study is aimed at investigating the expression of Met and YAP in gastric cancer and their impact on clinical prognosis. Methods. Tissue samples and clinical data were collected from 89 patients with gastric cancer. Immunohistochemistry was performed to quantify the expression of Met and YAP using tissue microarray. The correlation between the expressions of Met, YAP, and clinicopathological characteristics of patients was determined using a chi-square test. Survival analysis was conducted using the Kaplan-Meier method, while multivariate survival analysis was performed using the Cox proportional hazard model. Bioinformatics analysis was carried out by downloading chip data from TCGA. Results. The expression levels of both Met and YAP were significantly higher in gastric cancer tissues compared to adjacent tissues (P

Abstract Background As a member of the HACEK group, Aggregatibacter segnis (A. segnis) is a fastidious Gram-negative coccobacillus that resides in the human oropharyngeal flora. Infective endocarditis caused by A. segnis is rarely reported. Case presentation A 31-year-old male was admitted to our hospital for a 3-month history of intermittent high fever, chills, and chest distress. On presentation, he was febrile and tachycardic but otherwise with stable vital signs. Physical examination revealed systolic murmurs in the aortic and mitral valve areas. Pitting edema was evident in the lower extremities. Transthoracic echocardiography demonstrated multiple vegetations in the mitral and aortic valves. Severe regurgitation of the aortic valve and left heart dysfunction were also detected. With the suspicion of infective endocarditis and heart failure, we immediately performed microbiological tests and arranged the cardiac replacement surgery. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and metagenomic next-generation sequencing (mNGS) identified A. segnis from the bloodstream. While the surgical specimen culture was negative, the mNGS was positive for A. segnis. The patient was treated with ceftriaxone for four weeks and discharged. He remained clinically well, with laboratory results restored. Conclusion This is the first report of A. segnis infective endocarditis that combined MALDI-TOF and metagenomic next-generation sequencing in the diagnosis. The hypothesis-independent molecular techniques can outperform conventional tools to prevent diagnostic delay.

ABSTRACT Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.

IntroductionDuring the coronavirus disease 2019 (COVID-19) pandemic, the early detection and isolation of individuals infected with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) through mass testing can effectively prevent disease transmission. SARS-CoV-2 nucleic acid rapid detection based on loop-mediated isothermal amplification (LAMP) may be appropriate to include in testing procedures.MethodsWe used 860 nasopharyngeal specimens from healthcare workers of Huashan Hospital and COVID-19 patients collected from April 7th to 21st, 2022, to assess the clinical diagnostic performance of the LAMP assay marketed by Shanghai GeneSc Biotech and compared it to the result of a rapid antigen test (RAT) head-to-head.ResultsOverall, the diagnostic performance of LAMP assay and RAT were as follows. The LAMP assay represented higher sensitivity and specificity than RAT, especially in the extracted RNA samples. The sensitivity was 70.92% and 92.91% for direct LAMP and RNA-LAMP assay, respectively, while the specificity was 99.86% and 98.33%. The LAMP assay had overall better diagnostic performance on the specimens with relatively lower Ct values or collected in the early phase (≤7 days) of COVID-19. The combination of LAMP assay and RAT improved diagnostic efficiency, providing new strategies for rapidly detecting SARS-CoV-2.ConclusionThe LAMP assay are suitable for mass screenings of SARS-CoV-2 infections in the general population.

Abstract Aimed at the problem that the quality of the formation of aero-rotor blades with complex shaped structures is difficult to predict due to the coupling of each physical field in the process of electrochemical machining, a mathematical model of electrochemical machining characterized by the conductivity of the multi-physics field is established firstly by studying the coupling action mechanism of the flow field and temperature field on electric field conductivity in the machining process. Then, utilizing the Runge–Kutta method, the relationship between the conductivity and the machine path is analysed; Finally, based on this relationship, the multi-physics field electrochemical machining erosion model is compared with the traditional single electric field electrochemical machining erosion model. The results show that the error of the multi-physical field coupling prediction model proposed in this study is in the range of 1.27–2.35%, while the accuracy of the single electric field prediction model is in the range of 4.35–5.88%. The theoretical value of the multi-physics field coupling simulation is closer to the measured value of the test and can accurately simulate the actual electrochemical machining process, which can provide a theoretical basis for the design of cathode tools and parameter optimization in the actual processing process and is of great significance to improve the quality and efficiency of the electrochemical machining of aero-rotor blades.

Background. Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy. Methods. The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between “hot” and “cold” tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines. Results. The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells. Conclusion. Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment.

Abstract Background Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered. Methods We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR). Results 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC. Conclusion This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

Abstract Background Fixed appliances have been the mainstream for orthodontic treatment, while clear aligners, such as Invisalign system, have become increasingly popular. The prevalence of apical root resorption (ARR) in patients with clear aligners is still controversial. The aim of this study was to investigate and compare the prevalence and severity of ARR in patients treated with clear aligners and fixed appliances using cone beam computed tomography (CBCT). Materials and methods A total of 373 roots from 70 subjects, with similar baseline characteristics and the ABO discrepancy index scores (i.e., treatment difficulty), were included into two groups: the clear aligners group (Invisalign, Align Technology, California, USA) and fixed appliances group (Victory Series; 3 M Unitek, California, USA). Root length of each anterior tooth was measured on the CBCT images by two blinded investigators. The ARR on each tooth was calculated as the difference of root length before and after orthodontic treatment. Chi-square test and paired t test was used to compare the ARR between the two groups as well as before and after orthodontic treatments. Results Prevalence of ARR in the clear aligners group (56.30%) was significantly lower than that in the fixed appliances group (82.11%) (P

Activation of pro-σK processing requires a signaling protease SpoIVB that is secreted from the forespore into the space between the two cells during sporulation in Bacillus subtilis. Bypass of forespore protein C (BofC) is an inhibitor preventing the autoproteolysis of SpoIVB, ensuring the factor σK operates regularly at the correct time during the sporulation. However, the regulatory mechanisms of BofC on pro-σK processing are still unclear, especially in the aspect of the interaction between BofC and SpoIVB. Herein, the recombinant BofC (rBofC) was expressed in the periplasm by the E. coli expression system, and crystal growth conditions were obtained and optimized. Further, the crystal structure of rBofC was determined by X-ray crystallography, which is nearly identical to the structures determined by NMR and predicted by AlphaFold. In addition, the modeled structure of the BofC–SpoIVB complex provides insights into the molecular mechanism by which domain 1 of BofC occupies the active site of the SpoIVB serine protease domain, leading to the inhibition of the catalytical activity of SpoIVB and prevention of the substrate of SpoIVB (SpoIVFA) from binding to the active site.

A semirigid solar array is an efficient energy system on the surface of stratospheric airships for utilizing the solar energy, which we believe that it has succeeded in providing some impressive results for conceptual design. This paper developed a lightweight photovoltaic composite structure (LPCS) according to the characteristics of the stratospheric airship capsule. In order to improve the flexibility of the solar cell, we studied the mechanical properties in the different thicknesses of the honeycomb core for LPCS by FEM software and three-point bending test, and we also launched experiments to measure the temperature difference between upper and lower surfaces of the LPCS test samples under different solar radiation flux conditions. The experimental data were examined to evaluate the mechanical properties and thermal insulation performances of LPCS. Considering the quality of the whole structure, the paper finally comes up with the conclusion of the optimal thickness of the honeycomb core with further detailed descriptions.

OBJECTIVE:Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. METHODS:164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. RESULTS:There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P