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Abstract Background This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Methods A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan–Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. Results A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. Conclusions AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.

Abstract Hydrogen oxidation reaction in alkaline media is critical for alkaline fuel cells and electrochemical ammonia compressors. The slow hydrogen oxidation reaction in alkaline electrolytes requires large amounts of scarce and expensive platinum catalysts. While transition metal decoration can enhance Pt catalysts’ activity, it often reduces the electrochemical active surface area, limiting the improvement in Pt mass activity. Here, we enhance Pt catalysts’ activity without losing surface-active sites by using a Pd-Ru pair. Utilizing a mildly catalytic thermal pyrolysis approach, Pd-Ru pairs are decorated on Pt, confirmed by extended X-ray absorption fine structure and high-angle annular dark-field scanning transmission electron microscopy. Density functional theory and ab-initio molecular dynamics simulations indicate preferred Pd and Ru dopant adsorption. The Pd-Ru decorated Pt catalyst exhibits a mass-based exchange current density of 1557 ± 85 A g−1 metal for hydrogen oxidation reaction, demonstrating superior performance in an ammonia compressor.

Abstract Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions. Hybrid sequencing combines the best strengths of different technologies for a more comprehensive view of genomic/transcriptomic variations. Understanding each technology’s strengths and limitations is critical for translating cutting-edge technologies into clinical applications. In this study, we sequenced DNA and RNA libraries of reference samples using various targeted DNA and RNA panels and the whole transcriptome on both short-read and long-read platforms. This study design enables a comprehensive analysis of sequencing technologies, targeting protocols, and library preparation methods. Our expanded profiling landscape establishes a reference point for assessing current sequencing technologies, facilitating informed decision-making in genomic research and precision medicine.

Abstract Background Poor mood states pose the most frequent mental health, creating a considerable burden to global public health. Sedentary behavior is an essential factor affecting mood states, however, previous measures to reduce sedentary time in Chinese young adults have focused only on increasing physical activity (PA). Sedentary, PA, and sleep make up a person’s day from the standpoint of time use. It is not known whether reallocating sedentary time to different types of PA (e.g. daily PA and structured PA) or sleep during an epidemic has an effect on mood states. Therefore, this study aimed to examine the association between replacing sedentary time with different types of PA or sleep during the pandemic and the mood states of Chinese young adults and to further examine whether this association varies across sleep populations and units of replacement time. Method 3,579 young adults aged 18 to 25 years living in China and self-isolating at home during the COVID-19 outbreak were invited to complete an online questionnaire between February from 23 to 29, 2020. Subjects’ PA, sedentary time, and mood states were assessed using the International Physical Activity Questionnaire and the Chinese version of the Profile of Mood States, respectively. Participants also reported sleep duration and some sociodemographic characteristics. Participants were divided into short sleepers ( 9 h/d) based upon their reported sleep duration. Relevant data were analyzed using Pearson correlation analysis and isotemporal substitution model (ISM). Results Sedentary time was negatively associated with mood states in Chinese young adults during the pandemic (r = 0.140) and correlated strongest among short sleepers (r = 0.203). Substitution of sedentary time with structured PA was associated with good mood states (β=-0.28, 95% CI: -0.49, -0.08). Additionally, substituting sedentary time with daily PA (e.g. occupational PA, household PA) was also associated with good mood states among normal sleepers (β=-0.24, 95% CI: -0.46, -0.02). The substitution of sedentary time with sleep could bring mood benefits (β=-0.35, 95% CI: -0.47, -0.23). This benefit was particularly prominent among short sleepers. Furthermore, for long sleepers, replacing sedentary time with sleep time also resulted in significant mood benefits (β=-0.41, 95% CI: -0.69, -0.12). The longer the duration of replacing sedentary behavior with different types of PA or sleep, the greater the mood benefits. Conclusions A reallocation of as little as 10 min/day of sedentary time to different types of PA or sleep is beneficial for the mood states of young adults. The longer the reallocation, the greater the benefit. Our results demonstrate a feasible and practical behavior alternative for improving mood states of Chinese young adults.

Abstract The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.

Abstract Purpose To investigate the role of prognostic genes related to cisplatin resistance in ovarian cancer during disease progression. Method The gene expression profile of the NCI-60 cell line was acquired through comprehensive analysis of the GEO database accession GSE116439. We performed a thorough analysis of gene expression differences in samples from seven individuals exposed to cisplatin concentrations of 0 nM compared to seven samples exposed to 15000 nM over a 24-h period. Key genes were initially identified through LASSO regression, followed by their enrichment through differential gene function analysis (GO) and pathway enrichment analysis (KEGG). Subsequently, a prognostic risk model was established for these key genes. The prognostic model's performance was assessed through K-M survival curves and ROC curves. To examine the variance in immune cell infiltration between the high and low-risk groups, CIBERSORTx analysis was employed. Finally, validation of prognostic gene expression in cisplatin-resistant ovarian cancer was carried out using clinical samples, employing RT-qPCR and Western Blot techniques. Results A total of 132 differential genes were found between cisplatin resistance and control group, and 8 key prognostic genes were selected by analysis, namely VPS13B, PLGRKT, CDKAL1, TBC1D22A, TAP1, PPP3CA, CUX1 and PPP1R15A. The efficacy of the risk assessment model derived from prognostic biomarkers, as indicated by favorable performance on both Kaplan–Meier survival curves and ROC curves. Significant variations in the abundance of Macrophages M1, T cells CD4 memory resting, T cells follicular helper, and T cells gamma delta were observed between the high and low-risk groups. To further validate our findings, RT-qPCR and Western Blot analyses were employed, confirming differential expression of the identified eight key genes between the two groups. Conclusion VPS13B, TBC1D22A, PPP3CA, CUX1 and PPP1R15A were identified as poor prognostic genes of cisplatin resistance in ovarian cancer, while PLGRKT, CDKAL1 and TAP1 were identified as good prognostic genes. This offers a novel perspective for future advancements in ovarian cancer treatment, suggesting potential avenues for the development of new therapeutic targets.

Abstract Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

We study the almost everywhere pointwise convergence of the Boussinesq operator along sequences $ \{t_n\}_{n = 1}^\infty $ with $ \lim\limits_{n\rightarrow \infty} t_n = 0 $ in one dimension. We obtain a characterization of convergence almost everywhere when $ \{t_n\}\in l^{r, \infty}(\mathbb{N}) $ for all $ f\in H^s(\mathbb{R}) $ provided $ 0 < s < \frac12 $.

Objective: This study aimed to optimize the preparation process of blueberry juice and improve its antioxidant activity. Methods: Blueberry juice was prepared using a wet ultrafine grinding process and compound enzymolysis method. Response surface methodology was used to optimize the process parameters and analyze the antioxidant activity of blueberry juice. Results: There were significant differences in the juice yield and active substance content of blueberry juice under different solid-liquid ratios, crushing times, compound enzyme contents, and enzymatic hydrolysis times, with enzymatic hydrolysis time having the most significant impact on juice yield and anthocyanin content. The optimal process parameters for the wet ultrafine grinding process and compound enzymolysis method are solid-liquid ratio of 1∶1.7 (g/g), pulverization time of 8.00 min, compound enzyme content of 0.15%, and enzymatic hydrolysis time of 127 min. Under the control of these process conditions, the blueberry juice yield was 87.89%, with the contents of anthocyanin, total flavonoid and total phenol were 612.04 mg/L, 2.96 g/L and 3.43 g/L, respectively, and its antioxidant capacity was equivalent to 0.3% vitamin C when the addition amount is 1.6 mL. Conclusion: The wet ultrafine grinding process and compound enzymolysis method can improve the juice yield of blueberry juice, maximize the retention of its active substances, and enhance its antioxidant capacity.

Abstract Glioblastoma (GBM) is a highly aggressive, infiltrative malignancy that cannot be completely cured by current treatment modalities, and therefore requires more precise molecular subtype signatures to predict treatment response for personalized precision therapy. Expression subtypes of GBM samples from the Cancer Genome Atlas (TCGA) were identified using BayesNM and compared with existing molecular subtypes of GBM. Biological features of the subtypes were determined by single-sample gene set enrichment analysis. Genomic and proteomic data from GBM samples were combined and Genomic Identification of Significant Targets in Cancer analysis was used to screen genes with recurrent somatic copy-number alterations phenomenon. The immune environment among subtypes was compared by assessing the expression of immune molecules and the infiltration of immune cells. Molecular subtypes adapted to immunotherapy were identified based on Tumor Immune Dysfunction and Exclusion (TIDE) score. Finally, least absolute shrinkage and selection operator (LASSO) logistic regression was performed on the expression profiles of S2, S3 and S4 in TCGA-GBM and RPPA to determine the respective corresponding best predictive model. Four novel molecular subtypes were classified. Specifically, S1 exhibited a low proliferative profile; S2 exhibited the profile of high proliferation, IDH1 mutation, TP53 mutation and deletion; S3 was characterized by high immune scores, innate immunity and adaptive immune infiltration scores, with the lowest TIDE score and was most likely to benefit from immunotherapy; S4 was characterized by high proliferation, EGFR amplification, and high protein abundance, and was the most suitable subtype for bevacizumab. LASSO analysis constructed the best prediction model composed of 13 genes in S2 with an accuracy of 96.7%, and the prediction model consisting of 17 genes in S3 with an accuracy of 86.7%, and screened 14 genes as components of the best prediction model in S4 with an accuracy of 93%. To conclude, our study classified reproducible and robust molecular subtypes of GBM, and these findings might contribute to the identification of patients responding to immunotherapy, thereby improving GBM prognosis.

A method of gas chromatography-mass spectrometry (GC-MS) was established to determine the migration of dibutyl sebacate, dioctyl sebacate, diisooctyl sebacate, decanedioic acid bis(2,2,6,6-tetramethyl-4-piperidinyl)ester in water-based, acidic and alcoholic food simulants, and olive oil and chemical alternative solvents. The 95% ethanol and isooctane chemical substitution solutions were directly analyzed by GC-MS. The olive oil samples were extracted with acetonitrile followed by QuEChERS purification, and then analyzed by GC-MS. Other simulants (water, 4% acetic acid, 10% ethanol, 20% ethanol, and 50% ethanol) were extracted with n-hexane and then determined by GC-MS. The results showed that the method is well performed under optimized conditions, with the correlation coefficient (r2) greater than 0.995. The limits of detection and the limits of quantitation of the four sebacic acid ester compounds in water, 4% acetic acid, 10% ethanol, 20% ethanol, 50% ethanol, 95% ethanol, isooctane, and olive oil simulants are 0.1-0.2 mg/kg, 0.3-0.5 mg/kg, respectively. Migration experiments on plastic samples were conducted, and spiking experiments at three concentration levels of 0.30, 2.0, 4.0 mg/kg in water, 4% acetic acid, 10% ethanol, 20% ethanol, 50% ethanol, 95% ethanol, and isooctane food simulants, and three concentration levels of 0.50, 2.0, 4.0 mg/kg in olive oil food simulants were carried out. The spiking recoveries range from 92.5% to 108%, and the relative standard deviations (RSDs) are 2.4%-8.8%. The method solves the problem that decanedioic acid bis(2,2,6,6-tetramethyl-4-piperidinyl)ester cannot be extracted into n-hexane in 4% acetic acid by adjusting pH value using ammonium hydroxide, the optimal pH range was determined by comparing the responses of four targets at different pH values. QuEChERS was firstly used for migration experiments of sebacic acid esters in food contact materials to solve the turbidity and partial oil precipitation of olive oil simulants in the concentration process after extraction. By optimizing the QuEChERS filling material, the interference of organic acids, fatty acids, sugar and other impurities on the targets were reduced, producing greater separation effect of the targets. The separation efficiency of four chromatographic columns with different polarity was compared, and the DB-17HT column was selected to detect the four sebacic acid esters simultaneously. Plastics such as polypropylene, polyethylene terephthalic acid terephthalate, polyvinyl chloride, composite membranes, paper cups, recycled PET and recycled PVC were collected and migration experiments were carried out, the migration of sebacic acid esters in these plastics materials was investigated. This method is highly sensitive, precise, and accurate, fully meeting the requirement for determining the migration of the sebacic acid esters in food contact materials and their products.

Regular physicochemical and microbiological properties and volatile flavors of Sichuan Wu xiang-style sausages collected from Chengdu City were analyzed and used to reveal the quality characteristics of Sichuan Wu xiang-style sausage. The results showed that moisture content was 11.73%±1.64%, pH value was 5.68±0.06, TBARS value was 1.47±0.48 mg/kg, nitrite content was 1.31±0.12 mg/kg, and L*, a*, and b* was 48.12±1.46, 16.08±0.91, 18.31±0.73 respectively. The aerobic plate count, suspected staphylococci count, suspected lactic acid bacteria count, and Enterobacteriaceae count was 7.09±0.14, 5.74±0.23, 7.64±0.14 and 4.27±0.15 lg CFU/g, respectively. 97 kinds of volatile compounds were totally detected from Sichuan Wu xiang-style sausage samples, and 22 shared volatile compounds with odor activity value (OAV) greater than 1 were regarded as the main volatile flavors. Furthermore, it was showed that (+)-limonene, linalool and artemisia brain contributed most to the typical flavor of Wu xiang-style sausage through the loading plot of principal component analysis, imparting citrus, mint, floral, lavender, liquorice, and aniseed odors. The results obtained revealed the main volatile compounds and typical flavor characteristics of Sichuan Wu xiang-style sausage, and laid foundations for further researches on the flavor characteristics of Sichuan Wu xiang-style sausage.

Abstract Objective To investigate the physical fitness level and health behavior status of preschool children in China, explore the relationship between physical fitness and health behavior, and further reveal the main factors affecting health behavior, to provide a reference for improving the physical fitness level of preschool children and maintaining healthy behavior. Methods A total of 755 preschool children (394 boys and 361 girls, aged 4.52 ± 1.11 years) were selected from Chongqing and Liupanshui in China by cluster random sampling method for questionnaire survey and physical monitoring, and SPSS21.0 software was used to process and analyze the data. Results (1) Heart rate (p = 0.015), protein content (p

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

In order to solve the enzymatic browning phenomenon in the pulping unit of Lonicera caerulea fruits and improve its utilization value. The main phenolic substrates involved in the enzymatic browning reaction in the pulping process of Lonicera caerulea fruits and the inhibition ability were investigated, and the interactions between phenolic substrates and epicatechin on the reaction of polyphenol oxidase (PPO) were analyzed and its mechanism of enzymatic browning was also determined. The three most effective inhibitors were further selected by comparing the effects of ascorbic acid, L-cysteine, calcium chloride, EDTA-2Na, and citric acid additions on the browning inhibition rate. The results showed that epicatechin was the primary influencing factor involved in enzymatic browning in the pulping process of Lonicera caerulea fruits, and the quenching mechanism of epicatechin on PPO was static quenching. The response surface optimization test determined the optimal combination of composite inhibitors as 0.11% ascorbic acid, 0.11% L-cysteine, and 0.08% EDTA-2Na, and the browning inhibition rate of Lonicera caerulea fruits juice under this condition was 93.17%. It indicates that the above composite inhibitors can inhibit the enzymatic browning in the pulping process of Lonicera caerulea fruits.

Abstract Objective Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. Methods In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. Results After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. Conclusions Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.

Introduction: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. Methods: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. Results: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. Conclusion: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.

Abstract Background A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. Methods A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. Results In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR

Graphitic carbon nitride (g-C3N4) is a widely studied visible-light-active photocatalyst for low cost, non-toxicity, and facile synthesis. Nonetheless, its photocatalytic efficiency is below par, due to fast recombination of charge carriers, low surface area, and insufficient visible light absorption. Thus, the research on the modification of g-C3N4 targeting at enhanced photocatalytic performance has attracted extensive interest. A considerable amount of review articles have been published on the modification of g-C3N4 for applications. However, limited effort has been specially contributed to providing an overview and comparison on available modification strategies for improved photocatalytic activity of g-C3N4-based catalysts in antibiotics removal. There has been no attempt on the comparison of photocatalytic performances in antibiotics removal between modified g-C3N4 and other known catalysts. To address these, our study reviewed strategies that have been reported to modify g-C3N4, including metal/non-metal doping, defect tuning, structural engineering, heterostructure formation, etc. as well as compared their performances for antibiotics removal. The heterostructure formation was the most widely studied and promising route to modify g-C3N4 with superior activity. As compared to other known photocatalysts, the heterojunction g-C3N4 showed competitive performances in degradation of selected antibiotics. Related mechanisms were discussed, and finally, we revealed current challenges in practical application. HIGHLIGHTS Photocatalysis has been explored as an effective way to remove antibiotics.; g-C3N4 shows advantageous features for photocatalysis.; Modification of g-C3N4 improves photocatalytic performance.; Heterostructure formation is a promising modification route to modify g-C3N4.; Challenges and future perspectives in photocatalytic reaction for antibiotics removal were discussed.;

Abstract Background Our study aims to evaluate the genetic and phenotypic spectrum of Frontotemporal dementia (FTD) gene variant carriers in Chinese populations, investigate mutation frequencies, and assess the functional properties of TBK1 and OPTN variants. Methods Clinically diagnosed FTD patients underwent genetic analysis through exome sequencing, repeat-primed polymerase chain reaction, and Sanger sequencing. TBK1 and OPTN variants were biologically characterized in vitro using immunofluorescence, immunoprecipitation, and immunoblotting analysis. The frequencies of genes implicated in FTD in China were analyzed through a literature review and meta-analysis. Results Of the 261 Chinese FTD patients, 61 (23.4%) carried potential causative variants in FTD-related genes, including MAPT (n = 17), TBK1 (n = 7), OPTN (n = 6), GRN (n = 6), ANXA11 (n = 4), CHMP2B (n = 3), C9orf72 GGGGCC repeats (n = 2), CYLD (n = 2), PRNP (n = 2), SQSTM1 (n = 2), TARDBP (n = 2), VCP (n = 1), CCNF (n = 1), CHCHD10 (n = 1), SIGMAR1 (n = 1), CHCHD2 (n = 1), FUS (n = 1), TMEM106B (n = 1), and UBQLN2 (n = 1). 29 variants can be considered novel, including the MAPT p.D54N, p.E342K, p.R221P, p.T263I, TBK1 p.E696G, p.I37T, p.E232Q, p.S398F, p.T78A, p.Q150P, p.W259fs, OPTN p.R144G, p.F475V, GRN p.V473fs, p.C307fs, p.R101fs, CHMP2B p.K6N, p.R186Q, ANXA11 p.Q155*, CYLD p.T157I, SQSTM1 p.S403A, UBQLN2 p.P509H, CCNF p.S160N, CHCHD10 p.A8T, SIGMAR1 p.S117L, CHCHD2 p.P53fs, FUS p.S235G & p.S236G, and TMEM106B p.L144V variants. Patients with TBK1 and OPTN variants presented with heterogeneous clinical phenotypes. Functional analysis demonstrated that TBK1 I37T and E232Q mutants showed decreased autophosphorylation, and the OPTN phosphorylation was reduced by the TBK1 I37T mutant. The OPTN-TBK1 complex formation was enhanced by the TBK1 E696G mutant, while OPTN R144G and F475V mutants exhibited reduced recruitment to autophagosomes compared to the wild-type. The overall frequency of TBK1 and OPTN in Chinese FTD patients was 2.0% and 0.3%, respectively. Conclusions Our study demonstrates the extensive genetic and phenotypic heterogeneity of Chinese FTD patients. TBK1 mutations are the second most frequent cause of clinical FTD after MAPT in the Chinese.

To improve the quality of wheat flour and increase the protein content of wheat foods, soybean oligopeptide, which had nutritional value and biological activity, was added to wheat starch. The pasting properties, rheological properties, thermodynamic properties and structural properties of wheat starch were investigated. The results showed that the addition of soybean oligopeptide (0%~40%) decreased the peak viscosity, trough viscosity and final viscosity of the complexes, and increased the pasting temperatures significantly (P

Abstract Background Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them. Methods We collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB. Results OLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased. Conclusions A lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.

Abstract Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer treatment. Mitochondria, as pivotal organelles, play a crucial role in the metabolic regulation of tumor cells, and their morphological and functional alterations are intricately linked to the biological characteristics of tumors. As a key regulatory subunit of mitochondria, mitochondrial inner membrane protein (IMMT), plays a vital role in degenerative diseases, but its role in tumor is almost unknown. The objective of this research was to investigate the roles that IMMT play in the development and progression of breast cancer (BC), as well as to elucidate the underlying biological mechanisms that drive these effects. In this study, it was confirmed that the expression of IMMT in BC tissues was significantly higher than that in normal tissues. The analysis of The Cancer Genome Atlas (TCGA) database revealed that IMMT can serve as an independent prognostic factor for BC patients. Additionally, verification in clinical specimens of BC demonstrated a positive association between high IMMT expression and larger tumor size (> 2 cm), Ki-67 expression (> 15%), and HER-2 status. Furthermore, in vitro experiments have substantiated that the suppression of IMMT expression resulted in a reduction in cell proliferation and alterations in mitochondrial cristae, concomitant with the liberation of cytochrome c, but it did not elicit mitochondrial apoptosis. Through Gene Set Enrichment Analysis (GSEA) analysis, we have predicted the associated metabolic genes and discovered that IMMT potentially modulates the advancement of BC through its interaction with 16 metabolic-related genes, and the changes in glycolysis related pathways have been validated in BC cell lines after IMMT inhibition. Consequently, this investigation furnishes compelling evidence supporting the classification of IMMT as prognostic marker in BC, and underscoring its prospective utility as a novel target for metabolic therapy.

Abstract Background Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear. Methods The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry. Results Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis. Conclusions These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis.

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, a novel ferroptosis inhibitor, is a well-described clinical drug widely used. However, its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear. In this study, we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism. A single intraperitoneal injection of DOX (15 mg/kg) was administrated to establish DOX-induced cardiotoxicity. The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe2+ and ROS overload, which resulted in ferroptosis. CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1. Interestingly, idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX. Idebenone could form stable hydrogen bonds with FSP1 protein at K355, which may influence its association with ubiquitin. The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation. In conclusion, this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1, making it a potential clinical drug for patients receiving DOX treatment.

Background NFE2L2 (nuclear factor erythroid-2-related factor-2) encodes a basic leucine zipper (bZIP) transcription factor and exhibits variations in various tumor types, including lung cancer. In this study, we comprehensively investigated the impact of simultaneous mutations on the survival of NFE2L2-mutant lung cancer patients within specific subgroups.

Abstract The Crumbs protein (CRB) family plays a crucial role in maintaining the apical–basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes.

Abstract Background C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. Methods Accordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords ‘IL-8’ or ‘interleukin-8’ or ‘CXCL8’, ‘polymorphism’ and ‘cancer’ or ‘tumor’. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay. Results About 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079–1.459), P heterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046–1.666), P heterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P

Abstract Introduction Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase. Materials and methods This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi’an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data. Results Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration. Conclusion Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.

Abstract With the swift advancement of the global digital economy, data has emerged as a critical component in fostering the integration of large enterprises with small and medium-sized enterprises (SMEs). Nevertheless, due to disparities in resources and capabilities between these entities, there is a deficiency in the willingness to share data, hindering the full actualization of data’s potential value. Hence, it is imperative to facilitate a novel cooperative development paradigm wherein platforms enable data sharing among large enterprises and SMEs. In this paper, we construct a tripartite evolutionary game model encompassing large enterprises, SMEs, and digital platforms, examine the evolutionary stable strategies adopted by these entities in the data sharing, and use numerical simulation to explore the system’s evolutionary stability under various influencing factors. Contrasting with prior research, this study considers the heterogeneity of enterprise scale and delves into the data sharing dynamics between large enterprises and SMEs. Simultaneously, it positions the digital platform as a player in the game, examining its impact on data sharing among the enterprises. Findings indicate that: (1) SMEs exhibit greater eagerness for data sharing compared to large enterprises, which display a U-shaped influence during the process; (2) Digital platforms are particularly sensitive to costs, with the platform’s initiative and the service quality will affect enterprises strategic choices; (3) Government subsidies positively encourage tripartite cooperation, and robust data security governance framework is crucial for enterprises. Finally, based on the results of the study and combining with the current situation of digital economy development, it puts forward the suggestions for promoting platforms to empower large enterprises and SMEs to realize data sharing and the prospects for future research.

Abstract Structural integrity is essential for safety in infrastructure, as it can help prevent catastrophic failures and financial losses. The significance of vibration-based damage detection has grown substantially in fields such as civil and mechanical engineering. Concurrently, the advancements in computational capacities have facilitated the integration of machine learning into damage detection processes through post-processing algorithms. Nevertheless, these require extensive data from structure-affixed sensors, raising computational requirements. In an effort to address this challenge, we propose a novel approach utilizing a pre-trained convolutional neural network (CNN) based on images to identify and assess structural damage. This method involves employing wavelet transform and scalograms to convert numerical acceleration data into image data, preserving spatial and temporal information more effectively compared to conventional Fourier transform frequency analysis. Six acceleration data channels are collected from carefully chosen nodes on a mini bridge model and a corresponding finite element bridge model, to train the CNN. The efficiency of training is further enhanced by applying transfer machine learning through two pre-trained CNNs, namely Alexnet and Resnet. We evaluate our method using different damage scenarios, and both Alexnet and Resnet show prediction accuracies over 90%.

Abstract Background Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). Methods TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2 G2019S) and LRRK2 knockout (Lrrk2 −/−) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. Results The Lrrk2 −/−-HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p

Abstract Background The clinical manifestations and prognosis of hemodialysis patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during the Omicron wave of the pandemic infection were still unclear. This study investigated the clinical characteristics of patients undergoing maintenance hemodialysis (MHD) infected with it. Methods This retrospective single-center study included 151 patients undergoing MHD. Healthcare workers were selected as control group were assessed from December 1, 2022 to March 31, 2023. Clinical data, laboratory test results, treatment protocols, and prognoses were collected and analyzed. Results The study population included 146 patients with MHD, 93 (63.7%) of whom were infected with SARS-CoV-2. The number of non-severe, severe, and critical cases was 84 (90.3%), 4 (4.3%), and 5 (5.3%), respectively. Six patients (6.5%) died during the study period. The main symptoms of SARS-CoV-2 infection, including fever, cough, and fatigue, were less common in patients with MHD than the controls. During SARS-CoV-2 infection, the C-reactive protein (2.9 vs. 11.8 mg/dl, p

Abstract Background The authors sought to examine the impact of the K-variant of butyrylcholinesterase (BCHE-K) carrier status on age-at-diagnosis of Alzheimer disease (AD) in APOE4 carriers. Methods Patients aged 50–74 years with cerebrospinal fluid (CSF) biomarker-confirmed AD, were recruited to clinical trial (NCT03186989 since June 14, 2017). Baseline demographics, disease characteristics, and biomarkers were evaluated in 45 patients according to BCHE-K and APOE4 allelic status in this post-hoc study. Results In APOE4 carriers (N = 33), the mean age-at-diagnosis of AD in BCHE-K carriers (n = 11) was 6.4 years earlier than in BCHE-K noncarriers (n = 22, P

Abstract In heterogeneous catalysis catalyst activation is often observed during the reaction process, which is mostly attributed to the induction by reactants. In this work we report that surface structure of molybdenum nitride (MoN x ) catalyst exhibits a high dependency on the partial pressure or concentration of reaction products i.e., CO and H2O in reverse water gas-shift reaction (RWGS) (CO2:H2 = 1:3) but not reactants of CO2 and H2. Molybdenum oxide (MoO x ) overlayers formed by oxidation with H2O are observed at reaction pressure below 10 mbar or with low partial pressure of CO/H2O products, while CO-induced surface carbonization happens at reaction pressure above 100 mbar and with high partial pressure of CO/H2O products. The reaction products induce restructuring of MoN x surface into more active molybdenum carbide (MoC x ) to increase the reaction rate and make for higher partial pressure CO, which in turn promote further surface carbonization of MoN x . We refer to this as the positive feedback between catalytic activity and catalyst activation in RWGS, which should be widely present in heterogeneous catalysis.

Abstract Objective To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. Materials and methods LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40

Abstract Objective Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. Methods This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. Results A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan–Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). Conclusions Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients’ outcome. Trial registration This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020).

Abstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates in the nucleus and cytoplasm, contributing to the onset of amyotrophic lateral sclerosis. In this study, we evaluate the effect of graphene quantum dots (GQDs) with different functional groups on TDP-43’s phase separation and aggregation in various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate the nuclear envelope, inhibiting the assembly of TDP-43 nuclear bodies and stress granules under oxidative stress or hyperosmotic environments, and reduce amyloid aggregates and disease-associated phosphorylation of TDP-43. Mechanistic analysis reveals GQDs-Cl and Cl-GQDs-OH modulate TDP-43 phase separation through hydrophobic and electrostatic interactions. Our findings highlight the potential of GQDs-Cl and Cl-GQDs-OH in modulating nuclear protein condensation and pathological aggregation, offering direction for the innovative design of GQDs to modulate protein phase separation and aggregation.

Highlights The boosted heterogeneous interfaces in titanium nitride (TiN) nanotube/polydimethylsiloxane (PDMS) composite contributed to strong polarization loss relaxation ability. The TiN nanotubes/PDMS composite possessed both good impedance matching behavior and strong dielectric loss ability in wide temperature spectrum. The TiN nanotubes/PDMS composite exhibited excellent EMWA performances (effective absorption bandwidth value of 3.23 GHz and minimum reflection loss value of − 44.15 dB) at the varied temperature from 298 to 573 K.

Abstract Background A better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-β N-glycosylation as a potential biomarker for breast cancer diagnosis. Methods DSHp-β chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-β N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves. Results 95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-β N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p

The treatment time window for acute cerebral infarction in global guidelines is within 24 h. We report a patient who was admitted to the hospital and underwent endovascular treatment reaching 40 h. During vascular examination, the thrombus moved to distant segment, and then the surgeon quickly performed endovascular treatment. The patient ultimately achieved a good outcome. This case indicates that thrombus is moveable at any time, we expected to provide advice to clinical doctors that vascular examination should also be arranged as soon as possible to clarify the etiology in stroke patients especially with low NIHSS scores.

Summary: Midbrain organoids provide an innovative cellular source for transplantation therapies of neurodegenerative diseases. Here, we present a protocol for midbrain organoid-derived cell transplantation into a Parkinson’s disease mouse model. We describe steps for midbrain organoid generation, single-cell suspension preparation, and cell transplantation. This approach is valuable for studying the efficacy of midbrain organoids as a potential cellular source for restoring motor function.For complete details on the use and execution of this protocol, please refer to Fu et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

This study examines the evolutionary trends in preference focus and satisfaction among real-time crowdsourced logistics platform riders (hereafter referred to as riders) in China since the outbreak of the COVID-19 pandemic. By analyzing real-time comments from 5,652 riders and applying the Latent Dirichlet Allocation (LDA) model to identify riders’ preferences and calculate their attention levels, combined with riders’ actual ratings to infer satisfaction levels (ranging from very dissatisfied to satisfied), this research for the first time explores the changing patterns of riders’ preferences and their attention and satisfaction trends in the pandemic context from a long-term dynamic perspective. The findings reveal that riders prioritize interaction quality; the range of fluctuation in average attention levels is large when high and small when low; attention to platform management, system utility, and rider relationships is on the rise, whereas interest in other preferences is declining; there is a significant correlation between rider attention and platform policies; and social media and related public opinion influence riders’ preferences. These insights are instrumental for the platform to adjust the policy direction duly and meet the core demands of riders according to the limited priority.