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Abstract Background Shigella flexneri (S. flexneri) is a common intestinal pathogenic bacteria that mainly causes bacillary dysentery, especially in low socioeconomic countries. This study aimed to apply cold atmospheric plasma (CAP) on S. flexneri directly to achieve rapid, efficient and environmentally friendly sterilization. Methods The operating parameters of the equipment were determined by plasma diagnostics. The plate count and transmission electron microscope were employed to calculate bacterial mortality rates and observe the morphological damage of bacterial cells. Measurement of intracellular reactive oxygen species (ROS) and superoxide anions were detected by 2,7-dichlorodihydrofluorescein (DCFH) and Dihydroethidium fluorescence probes, respectively. The fluorescence intensity (a. u.) reflects the relative contents. Additionally, the experiment about the single effect of temperature, ultraviolet (UV), and ROS on bacteria was conducted. Results The peak discharge voltage and current during plasma operation were 3.92kV and 66mA. After discharge, the bacterial mortality rate of 10, 20, 30 and 40 s of plasma treatment was 60.71%, 74.02%, 88.11% and 98.76%, respectively. It was shown that the intracellular ROS content was proportional to the plasma treatment time and ROS was the major contributor to bacterial death. Conclusion In summary, our results illustrated that the plasma treatment could inactivate S. flexneri efficiently, and the ROS produced by plasma is the leading cause of bacterial mortality. This highly efficient sterilization method renders plasma a highly promising solution for hospitals, clinics, and daily life.

Abstract Background Colorectal cancer (CRC) is one of the most common malignancies and is characterized by reprogrammed metabolism. Ferroptosis, a programmed cell death dependent on iron, has emerged as a promising strategy for CRC treatment. Although small nucleolar RNAs are extensively involved in carcinogenesis, it is unclear if they regulate ferroptosis during CRC pathogenesis. Methods The dysregulated snoRNAs were identified using published sequencing data of CRC tissues. The expression of the candidate snoRNAs, host gene and target gene were assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and western blots. The biological function of critical molecules was investigated using in vitro and in vivo strategies including Cell Counting Kit-8 (CCK8), colony formation assay, flow cytometry, Fe2+/Fe3+, GSH/GSSG and the xenograft mice models. The ribosomal activities were determined by polysome profiling and O-propargyl-puromycin (OP-Puro) assay. The proteomics was conducted to clarify the downstream targets and the underlying mechanisms were validated by IHC, Pearson correlation analysis, protein stability and rescue assays. The clinical significance of the snoRNA was explored using the Cox proportional hazard model, receiver operating characteristic (ROC) and survival analysis. Results Here, we investigated the SNORA56, which was elevated in CRC tissues and plasma, and correlated with CRC prognosis. SNORA56 deficiency in CRC impaired proliferation and triggered ferroptosis, resulting in reduced tumorigenesis. Mechanistically, SNORA56 mediated the pseudouridylation of 28 S rRNA at the U1664 site and promoted the translation of the catalytic subunit of glutamate cysteine ligase (GCLC), an indispensable rate-limiting enzyme in the biosynthesis of glutathione, which can inhibit ferroptosis by suppressing lipid peroxidation. Conclusions Therefore, the SNORA56/28S rRNA/GCLC axis stimulates CRC progression by inhibiting the accumulation of cellular peroxides, and it may provide biomarker and therapeutic applications in CRC.

AbstractInflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

AbstractBackground The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients.Patients and methods This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data.Results We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients.Conclusion Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

AbstractBackground We discovered that vitiligo was associated with sexual dysfunction in clinical diagnosis and treatment; however, no further analysis had been performed due to a lack of data.Objective This study aimed to clarify the relationship between vitiligo and sexual dysfunction.Methods We searched six databases (PubMed, Embase, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang Data Knowledge Service Platform) for nearly 40 years.Results According to the search strategy, 91 relevant studies were retrieved, of which 4 were included in the analysis. The Arizona Sexual Experience Scale (ASEX) score (mean difference [MD] 4.96, 95% confidence interval [CI] 2.78–7.13, p

Abstract The past decade has witnessed rapid progress in deep learning for molecular design, owing to the availability of invertible and invariant representations for molecules such as simplified molecular-input line-entry system (SMILES), which has powered cheminformatics since the late 1980s. However, the design of elemental components and their structural arrangement in solid-state materials to achieve certain desired properties is still a long-standing challenge in physics, chemistry and biology. This is primarily due to, unlike molecular inverse design, the lack of an invertible crystal representation that satisfies translational, rotational, and permutational invariances. To address this issue, we have developed a simplified line-input crystal-encoding system (SLICES), which is a string-based crystal representation that satisfies both invertibility and invariances. The reconstruction routine of SLICES successfully reconstructed 94.95% of over 40,000 structurally and chemically diverse crystal structures, showcasing an unprecedented invertibility. Furthermore, by only encoding compositional and topological data, SLICES guarantees invariances. We demonstrate the application of SLICES in the inverse design of direct narrow-gap semiconductors for optoelectronic applications. As a string-based, invertible, and invariant crystal representation, SLICES shows promise as a useful tool for in silico materials discovery.

Abstract This study proposes a space vector pulse width modulation (SVPWM) driving method for the switched reluctance motor (SRM), which enables the use of a standard full‐bridge power converter to drive a three‐phase SRM with a ring structure, in place of the traditional asymmetric H‐bridge (AHB). Based on this driving topology, the SVPWM approach is employed to drive the SRM, and its performance is compared with that of the conventional SRM driving method utilising the AHB. The findings indicate that the SVPWM method can effectively reduce torque ripple in the SRM. Moreover, the experimental validation performed to verify the proposed driving topology and method yields results that closely align with the simulated outcomes.

Abstract To further evaluate the causal relationships between inflammatory cytokines and migraine, we conducted a bidirectional, two-sample Mendelian randomization (MR) analysis using genetic data from publicly available genome-wide association studies (GWAS). We used several MR methods, including random-effect inverse-variance weighting (IVW), weighted median, MR-Egger, to test the causal relationships. Sensitivity analyses were also conducted to evaluate the robustness of the results. The results showed that hepatocyte growth factor (HGF) was positively associated with the risk of migraine (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001–1.008; P = 0.022). In addition, Interleukin-2 (IL-2) was considered a downstream consequence of migraine (OR, 0.012; 95% CI, 0.000–0.0929; P = 0.046). These findings suggest that HGF may be a factor associated with the etiology of migraine, while IL-2 is more likely to be involved in the downstream development of migraine.

Abstract It is commonly accepted that host genes show high methylation in cervical intraepithelial neoplasia 3 (CIN3) or worse (CIN3+). However, study quality varies, as does the clinical performance of markers in different populations. We aimed to validate candidate gene DNA methylation with standardized testing methods in the same batch of samples. We first compared the performance of 16 DNA methylation markers for detecting CIN3+ in the 82-sample training set, including 24 subjects with ≤ CIN1, 10 subjects with CIN2, 23 subjects with CIN3, and 25 subjects with cervical cancer (CC). Then five methylation markers were selected and subsequently validated among an independent set of 74 subjects, including 47 subjects with ≤ CIN1, 13 subjects with CIN2, 6 subjects with CIN3, and 8 subjects with CC. The results in the validation set revealed that methylation analysis of the SOX1 (SOX1 m ) showed a superior level of clinical performance (AUC = 0.879; sensitivity = 85.7%; specificity = 90.0%). SOX1 m had better accuracy than cytology, with a reduced referral rate (23.0% vs. 31.4%) and a lower number of overtreatment (5 vs. 13) cases among high-risk human papillomavirus (hrHPV)-positive women. Importantly, among hrHPV-positive and SOX1 m -negative women, only 1 CIN3 patient was at risk for follow-up after 1 year, whereas 1 CIN3 patient and 1 CC patient were at risk among hrHPV-positive and cytology-negative women. In this investigation, we screened 16 reported methylation markers to provide a basis for future studies related to potential precancerous lesion/cancer methylation markers in the Chinese population. The study also revealed that SOX1 m has optimal CIN3+ detection performance, suggesting that it may be a promising biomarker for detecting CIN3+ in the Chinese population.

Abstract Polyploidization is a major driver of genome diversification and environmental adaptation. However, the merger of different genomes may result in genomic conflicts, raising a major question regarding how genetic diversity is interpreted and regulated to enable environmental plasticity. By analyzing the genome-wide binding of 191 trans-factors in allopolyploid wheat, we identified like heterochromatin protein 1 (LHP1) as a master regulator of subgenome-diversified genes. Transcriptomic and epigenomic analyses of LHP1 mutants reveal its role in buffering the expression of subgenome-diversified defense genes by controlling H3K27me3 homeostasis. Stripe rust infection releases latent subgenomic variations by eliminating H3K27me3-related repression. The simultaneous inactivation of LHP1 homoeologs by CRISPR–Cas9 confers robust stripe rust resistance in wheat seedlings. The conditional repression of subgenome-diversified defenses ensures developmental plasticity to external changes, while also promoting neutral-to-non-neutral selection transitions and adaptive evolution. These findings establish an LHP1-mediated buffering system at the intersection of genotypes, environments, and phenotypes in polyploid wheat. Manipulating the epigenetic buffering capacity offers a tool to harness cryptic subgenomic variations for crop improvement.

Abstract Considering the non‐linear characteristics of both the input and output of photovoltaic (PV) modules and quasi‐Z‐source inverters, as well as the unpredictable natural factors such as large disturbances caused by changes in illumination and temperature, an average state model for the PV quasi‐Z‐source inverter is established. This paper uses the output current of photovoltaic module, DC‐link capacitor voltage and its integral as state variables, then an adaptive reaching law with second‐order sliding mode characteristics is designed by combining with power reaching law and variable speed reaching law. By using the sliding mode controller based on the adaptive reaching law to control the stability of the DC‐link voltage of the quasi‐Z‐source inverter and the small capacitor voltage ripple, the photovoltaic system can operate stably at the maximum power point when the temperature and illumination conditions change abruptly, and the grid‐connected effect is improved. Through SIMULINK and RT‐LAB real‐time simulation, the effectiveness of the proposed adaptive sliding mode control strategy is verified when the environment changes, which effectively improves the dynamic response speed and grid‐connected effect of the system, and ensures the global robustness of the grid‐connected system.

Abstract The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn’s disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P

Abstract. Background:. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients. Methods:. This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group. Results:. We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37–2.59, P

Abstract Aims The aim of the study was to explore the experiences of female new nurse managers during the COVID‐19 pandemic. Design This was a phenomenological study, and qualitative descriptive analysis was used. Methods New nurse managers were defined as new nurse managers with less than 3 years of management experience in this study. During November and December of 2021, 18 female new nurse managers were interviewed face‐to‐face with a semi‐structured interview guide in three municipal hospitals. The study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines for evaluating qualitative research reports. Data analysis was performed using Colaizzi's seven‐step method. Results Four main themes and 10 sub‐themes were extracted from the collected data. The four major themes were as follows: (1) a shift in stress; (2) work‐related physical and psychological discomfort; (3) reflection on the cause; (4) coping and struggles. Conclusions New nurse managers were experiencing great stress and exhaustion in their roles. It is important that they are helped to handle situations. Providing them with readily accessible support, addressing their psychosocial needs and addressing exhaustion is necessary. Considering their short management time, the hospital should provide adequate support in human, financial and material areas and provide training to help new nurse managers better adapt to their new roles. In addition, nurse directors should create a culture of mutual respect, identify workplace bullying and create a harmonious and cooperation‐oriented work environment for new nurse managers. Patient or Public Contribution No patient or public contribution.

The bromodomain and extra-terminal (BET) proteins act as “readers” for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes. BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2, and is involved in the regulation of cell cycle and apoptosis. Meanwhile, BET inhibitors (BETi) have regulatory effects on immune checkpoints, immune cells, and cytokine expression. The role of BET proteins and BETi in a variety of tumors has been studied. This paper reviews the recent research progress of BET and BETi in hematologic tumors (mainly leukemia, lymphoma and multiple myeloma) from cellular level studies, animal studies, clinical trials, drug combination, etc. BETi has a promising future in hematologic tumors, and future research directions may focus on the combination with other drugs to improve the efficacy.

Plain-woven carbon fiber-reinforced plastic (PW-CFRP) exhibits high damage tolerance and is widely used in the aerospace field. To address the issue that single-scale drilling simulation is difficult to reflect the practical drilling force due to the change in material elastic properties in PW-CFRP drilling simulation, this paper studies the prediction of elastic properties of PW-CFRP and multi-scale three-dimensional drilling simulation. Based on the prediction model of elastic performance parameters with periodic boundary conditions, the three-dimensional drilling simulation of PW-CFRP is carried out using the predicted material elastic performance parameters and the multi-scale finite element method, with experimental verification. The results show that the finite element method based on periodic boundary conditions can accurately predict the elastic constants of braided composites. For the woven unit cell, its boundary surface changes from plane to surface under shear load, and convex-concave warping deformation occurs. The PW-CFRP three-dimensional drilling simulation model, based on the stiffness prediction model, can accurately predict the axial force and torque during the drilling process. Under the same process parameters, the maximum relative errors between the simulation prediction and the experimental results of the drilling thrust force and torque are 14.2% and 8.5%, respectively. The multi-scale drilling simulation of PW-CFRP, from microscopic to mesoscopic to macroscopic, is realized.

Abstract Background and aim Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. Methods We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. Results Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. Conclusions IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.

Abstract Background β-Alanine is a precursor of many important pharmaceutical products and food additives, its market demand is continuously increasing nowadays. Whole-cell catalysis relying on the recombinant expression of key β-alanine synthesizing enzymes is an important method to produce β-alanine. Nevertheless, β-alanine synthesizing enzymes found so far have problems including easy inactivation, low expression or poor catalytic activity, and it remains necessary to develop new enzymes. Results Herein, we characterized an l-aspartate-α-decarboxylase, MpADC, from an aphid, Myzus persicae. It showed excellent catalytic activity at pH 6.0–7.5 and 37 °C. With the help of chaperone co-expression and N-terminal engineering guided by AlphaFold2 structure prediction, the expression and catalytic ability of MpADC in Escherichia coli were significantly improved. Using 50 g/L of E. coli cells expressing the MpADC-∆39 variant cultured in a 15-L fermenter, 232.36 g/L of β-alanine was synthesized in 13.5 h, with the average β-alanine yield of 17.22 g/L/h, which is best known so far. Conclusions Our research should facilitate the production of β-alanine in an environment-friendly manner.

Abstract Mitochondrial transfer regulates intercellular communication, and mitochondria regulate cell metabolism and cell survival. However, the role and mechanism of mitochondrial transfer in Cd-induced nonalcoholic fatty liver disease (NAFLD) are unclear. The present study shows that mitochondria can be transferred between hepatocytes via microtubule-dependent tunneling nanotubes. After Cd treatment, mitochondria exhibit perinuclear aggregation in hepatocytes and blocked intercellular mitochondrial transfer. The different movement directions of mitochondria depend on their interaction with different motor proteins. The results show that Cd destroys the mitochondria-kinesin interaction, thus inhibiting mitochondrial transfer. Moreover, Cd increases the interaction of P62 with Dynactin1, promotes negative mitochondrial transport, and increases intracellular lipid accumulation. Mitochondria and hepatocyte co-culture significantly reduced Cd damage to hepatocytes and lipid accumulation. Thus, Cd blocks intercellular mitochondrial transfer by disrupting the microtubule system, inhibiting mitochondrial positive transport, and promoting their negative transport, thereby promoting the development of NAFLD. Graphical Abstract

Abstract Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model’s efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

Abstract In complex industrial environments such as the Internet of Things in coal mines, large mechanical and electrical equipment can generate powerful impulsive noise, which can cause sudden errors. Because it is difficult to establish an accurate channel model, the performance of current error control techniques is limited. To enhance the reliability of information recovery in the Internet of Things in coal mines, the traditional method of shortening the communication distance between sensors is often utilized, but this can be costly. Therefore, this article proposes an intelligent signal processing method against impulsive noise interference that draws on the concept of the Artificial Intelligence of Things (AIoT) and incorporates deep learning technology. This method replaces the traditional sensor signal processing module with a Convolutional Neural Network (CNN), which learns the intricate mapping relationship between transmitted information and sensor signals in impulsive noise environments. Simulation results demonstrate that the proposed method outperforms the traditional sensor signal processing method in three impulsive noise environments by achieving a lower Bit Error Rate (BER). Moreover, this method adopts an improved lightweight neural network, which is more conducive to the deployment of mobile terminals in the Internet of Things.

Abstract This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90–0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86–0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94–1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association.

Abstract Overcoming distant metastasis stands as a paramount challenge in enhancing the outcomes of breast cancer treatments. Thus, delving deeper into comprehending the intricate mechanisms underlying breast cancer metastasis becomes imperative, offering potential avenues for pioneering therapeutic approaches. PRMT6, an arginine N-methyltransferase, possesses the ability to methylate both histone and non-histone proteins. It has been reported that methylation of non-histone proteins impacts their cellular localization, stability, and activation, consequently influencing tumor progression. However, the extent to which PRMT6-mediated non-histone protein methylation influences cancer cell metastasis, particularly in the context of breast cancer, remains elusive. In this study, we established that PRMT6 exerted a positive regulatory influence on breast cancer metastasis through both in vivo and in vitro experiments. Mechanistically, we innovatively revealed that PRMT6 asymmetrically di-methylated STAT3 at arginine 729 (STAT3 R729me2a). This modification proved indispensable for STAT3’s membrane localization, its interaction with JAK2, STAT3 Y705 phosphorylation, and PRMT6-driven cancer cell metastasis. From a clinical perspective, we unearthed the promising potential of STAT3 R729me2a as a robust prognostic marker for predicting the overall survival time of breast cancer patients. In terms of therapeutic intervention, we demonstrated the significant capability of the PRMT6 inhibitor, EPZ020411, to curtail breast cancer metastasis both in vivo and in vitro. In sum, our study unveils the pivotal biological role of PRMT6-mediated STAT3 R729me2a in breast cancer metastasis and underscores the prospective utility of PRMT6 inhibitors as effective therapeutic strategies against STAT3-driven metastatic breast cancer.

Although several pentatricopeptide repeat (PPR) proteins are involved in post-transcriptional processing of mitochondrial RNA, it is unclear which specific protein is involved in the RNA editing of ccmC in maize (Zea mays). Here we report the identification of the maize empty pericarp 601 (emp601) mutant and the map-based cloning of the Emp601 gene, which encodes an E2-type PPR protein that is targeted to mitochondria. A single-nucleotide deletion in the emp601 mutant caused a frameshift and introduced a premature stop codon into the predicted EMP601. This mutation was associated with reduced accumulation of mitochondrial complex III as well as with inhibition of growth and differentiation of basal endosperm transfer layer cells, leading to final degeneration of the embryo and endosperm. We determine that loss of EMP601 function prevents the C-to-U RNA editing of the mitochondrial transcript ccmC at position 358. EMP601 binds to the ccmC transcript and directly interacts with Multiple organellar RNA editing factor 8 and may be a component of the plant mitochondrial editosome. We conclude that EMP601 functions in RNA editing of mitochondrial ccmC transcripts and influences mitochondrial function and seed development.

Abstract Nemonoxacin is a novel non-fluorinated quinolone with strong antibacterial efficacy, but data of its effect on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is rare. This study was conducted to compare the efficacy of oral nemonoxacin with moxifloxacin in AECOPD outpatients. In this retrospective observational study, a total of 101 AECOPD outpatients initially treated with nemonoxacin or moxifloxacin from July 2021 to March 2022 were enrolled. We collected COPD assessment test (CAT), Transition Dyspnea Indices (TDI) scores, and exacerbations information during 24 weeks follow-up from the electronic medical records. Kaplan–Meier curve was used to analyze the time to the next moderate/severe exacerbation. Compared to the moxifloxacin group, changes in CAT scores and TDI scores were significantly higher in the nemonoxacin group, and the nemonoxacin group also had a greater probability to reach the minimal clinically important difference of CAT (71.40% vs. 97.80%, p

The red swamp crayfish (Procambarus clarkii) is the largest freshwater shrimp cultured in China. Protein is a critical factor affecting red swamp crayfish growth performance and feed cost. Too high or too low protein levels in feed negatively affect crustaceans. However, the results of the optimal dietary protein content of red swamp crayfish identified in different studies vary considerably. There are mainly two types of feed for red swamp crayfish on the market: extruded and pellet feed. There have been few reports on the impact of processing technique on red swamp crayfish. Many studies have shown that the growth-promoting effects of extruded and pellet feed on diverse aquatic animals differ considerably. Moreover, there have been few studies on the impact of different protein levels and processing techniques on the growth of aquatic species. This study aimed to investigate the effects of dietary protein levels and processing techniques on the growth performance, digestibility, and antioxidant capacity of red swamp crayfish. The two-factor experiment (4×2) with four different protein levels (28%, 30%, 32%, and 36%) and two processing techniques (expanded feed [EF] and pellet feed [PF]) was conducted for 13 weeks as a feeding trial, aiming to provide theoretical support for optimizing the feed formula and processing technique of red swamp crayfish. The results showed that the protein levels and processing technique significantly influenced the weight gain rate (WGR) and hepatosomatic index of red swamp crayfish (P

Computer systems and applications generate large amounts of logs to measure and record information, which is vital to protect the systems from malicious attacks and useful for repairing faults, especially with the rapid development of distributed computing. Among various logs, the anomaly log is beneficial for operations and maintenance (O&M) personnel to locate faults and improve efficiency. In this paper, we utilize a large language model, ChatGPT, for the log parser task. We choose the BERT model, a self-supervised framework for log anomaly detection. BERT, an embedded transformer encoder, with a self-attention mechanism can better handle context-dependent tasks such as anomaly log detection. Meanwhile, it is based on the masked language model task and next sentence prediction task in the pretraining period to capture the normal log sequence pattern. The experimental results on two log datasets show that the BERT model combined with an LLM performed better than other classical models such as Deelog and Loganomaly.

Sound source identification technology based on a microphone array has many application scenarios. The compressive beamforming method has attracted much attention due to its high accuracy and high-resolution performance. However, for the far-field measurement problem of large microphone arrays, existing methods based on fixed grids have the defect of basis mismatch. Due to the large number of grid points representing potential sound source locations, the identification accuracy of traditional grid adjustment methods also needs to be improved. To solve this problem, this paper proposes a sound source identification method based on adaptive grid splitting and refinement. First, the initial source locations are obtained through a sparse Bayesian learning framework. Then, higher-weight candidate grids are retained, and local regions near them are split and updated. During the iteration process, Green’s function and the source strength obtained in the previous iteration are multiplied to get the sound pressure matrix. The robust principal component analysis model of the Gaussian mixture separates and replaces the sound pressure matrix with a low-rank matrix. The actual sound source locations are gradually approximated through the dynamically adjusted sound pressure low-rank matrix and optimized grid transfer matrix. The performance of the method is verified through numerical simulations. In addition, experiments on a standard aircraft model are conducted in a wind tunnel and speakers are installed on the model, proving that the proposed method can achieve fast, high-precision imaging of low-frequency sound sources in an extensive dynamic range at long distances.

The advancement of artificial intelligence (AI) demands significant data and computational resources that have an adverse impact on the environment. To address this issue, a novel computing architecture that is both energy efficient and eco-friendly is urgently required. Edge computing has emerged as an increasingly popular solution to this problem. In this study, we explore the development history of edge computing and AI and analyze the potential of model quantization to link AI and edge computing. Our comparative analysis demonstrates that the quantization approach can effectively reduce the model’s size and accelerate model inference while maintaining its functionality, thereby enabling its deployment on edge devices. This research serves as a valuable guide and reference for future advancements in edge AI.

In this paper, we propose a novel approach for solving two-dimensional time-fractional advection–diffusion equations, where the fractional derivative is described in the Caputo sense. The discrete scheme is constructed based on the barycentric rational interpolation collocation method and the Gauss–Legendre quadrature rule. We employ the barycentric rational interpolation collocation method to approximate the unknown function involved in the equation. Through theoretical analysis, we establish the convergence rate of the discrete scheme and show its remarkable accuracy. In addition, we give some numerical examples, to illustrate the proposed method. All the numerical results show the flexible application ability and reliability of the present method.

Mastitis typically arises from bacterial invasion, where host cell apoptosis significantly contributes to the inflammatory response. Gram-positive bacteria predominantly utilize the virulence factor lipoteichoic acid (LTA), which frequently leads to chronic breast infections, thereby impacting dairy production and animal husbandry adversely. This study employed LTA to develop models of mastitis in cow mammary gland cells and mice. Transcriptomic analysis identified 120 mRNAs associated with endocytosis and apoptosis pathways that were enriched in the LTA-induced inflammation of the Mammary Alveolar Cells-large T antigen (MAC-T), with numerous differential proteins also concentrated in the endocytosis pathway. Notably, actin-related protein 2/3 complex subunit 3 (ARPC3), actin-related protein 2/3 complex subunit 4 (ARPC4), and the heat shock protein 70 (HSP70) are closely related. STRING analysis revealed interactions among ARPC3, ARPC4, and HSP70 with components of the apoptosis pathway. Histological and molecular biological assessments confirmed that ARPC3, ARPC4, and HSP70 were mainly localized to the cell membrane of mammary epithelial cells. ARPC3 and ARPC4 are implicated in the mechanisms of bacterial invasion and the initiation of inflammation. Compared to the control group, the expression levels of these proteins were markedly increased, alongside the significant upregulation of apoptosis-related factors. While HSP70 appears to inhibit apoptosis and alleviate inflammation, its upregulation presents novel research opportunities. In conclusion, we deduced the development mechanism of ARPC3, ARPC4, and HSP70 in breast inflammation, laying the foundation for further exploring the interaction mechanism between the actin-related protein 2/3 (ARP2/3) complex and HSP70.

Path planning is one of the core issues in the autonomous navigation of an Unmanned Surface Vehicle (USV), as the accuracy of the results directly affects the safety of the USV. Hence, this paper proposes a USV path planning algorithm that integrates an improved Particle Swarm Optimisation (PSO) algorithm with a Dynamic Window Approach (DWA). Firstly, in order to advance the solution accuracy and convergence speed of the PSO algorithm, a nonlinear decreasing inertia weight and adaptive learning factors are introduced. Secondly, in order to solve the problem of long path and path non-smoothness, the fitness function of PSO is modified to consider both path length and path smoothness. Finally, the International Regulations for Preventing Collisions at Sea (COLREGS) are utilised to achieve dynamic obstacle avoidance while complying with maritime practices. Numerical cases verify that the path planned via the proposed algorithm is shorter and smoother, guaranteeing the safety of USV navigation while complying with the COLREGS.

This study aims to unveil correlations between wastewater microbiota and the catchment-specific population health risk, specifically alcohol abuse, with smoking and obesity as confounding factors. Our study highlights the importance of extracting human-associated microbial communities from wastewater metagenomes by excluding environmental microorganisms, due to their irrelevance to human health. After excluding environmental microbes, we observed strong associations of all three health risk factors, including alcohol abuse, smoking and obesity, with the human gut microbiome in wastewater. The linear discriminant analysis effect size (LEfSe) analysis showed Lactococcus_A, Leuconostoc, Aeromicrobium, Akkermansia, Weissella, Limosilactobacillus, Klebsiella_A, Desulfovibrio and Cloacibacillus as potential microbial biomarkers for alcoholism, after accounting for the confounding effects of smoking and obesity. Functional annotations of microorganisms linked with lower alcoholism rates are primarily related to energy metabolism and intercellular communication. Microorganisms associated with higher alcoholism rates are predominantly involved in immune regulation and cellular DNA architecture. This study highlights the need for a comprehensive exploration of different health risk factors together to identify potential associations between the wastewater microbiome and population lifestyle.

Parking path optimization is the principal problem of automatic vertical parking (AVP); however, it is difficult to determine a collision avoiding, smooth, and accurate optimized parking path using traditional parking reference trajectory optimization methods. In order to implement high-performance automatic parking reference trajectory optimization, we establish an automatic parking reference trajectory optimization model using cubic spline interpolation, and we propose an improved immune shark smell optimization (IISSO) to solve it. Firstly, we take the length of the parking reference trajectory as the optimization objective, and we introduce an intelligent automatic parking path optimization model using cubic spline interpolation. Secondly, the improved immune shark optimization algorithm combines the immune, refraction, and Gaussian variation mechanisms, thus effectively improving its global optimization ability. The simulation results for the parking path optimization experiments indicate that the proposed IISSO has a higher optimization accuracy and faster calculation speed; hence, it can obtain a parking path with higher optimization performance.

Neutron diffraction instruments offer a platform for materials science and engineering studies at extended temperature ranges far from ambient. As one of the widely used neutron sample environment types, cryogenic furnaces are usually bulky and complex, and they may need hours of beamtime overhead for installation, configuration, cooling, and sample change, etc. To reduce the overhead time and expedite experiments at the state-of-the-art high-flux neutron source, we developed a low-cost, miniature, and easy-to-use cryogenic environment (77–473 K) for in situ neutron diffraction. A travel-size mug serves for the environment where the samples sit inside. Immediate cooling and an isothermal dwell at 77 K are realized on the sample by direct contact with liquid N2 in the mug. The designed Al inserts serve as the holder of samples and heating elements, alleviate the thermal gradient, and clear neutron pathways. Both a single-sample continuous measurement and multi-sample high-throughput measurements are demonstrated in this environment. High-quality and refinable in situ neutron diffraction patterns are acquired on model materials. The results quantify the orthorhombic-to-cubic phase transformation process in LiMn2O4 and differentiate the anisotropic lattice thermal expansions and bond length evolutions between rhombohedral perovskite oxides with composition variation.

In addressing the challenges of non-standardization and limited annotation resources in Chinese marine domain texts, particularly with complex entities like long and nested entities in coral reef ecosystem-related texts, existing Named Entity Recognition (NER) methods often fail to capture deep semantic features, leading to inefficiencies and inaccuracies. This study introduces a deep learning model that integrates Bidirectional Encoder Representations from Transformers (BERT), Bidirectional Gated Recurrent Units (BiGRU), and Conditional Random Fields (CRF), enhanced by an attention mechanism, to improve the recognition of complex entity structures. The model utilizes BERT to capture context-relevant character vectors, employs BiGRU to extract global semantic features, incorporates an attention mechanism to focus on key information, and uses CRF to produce optimized label sequences. We constructed a specialized coral reef ecosystem corpus to evaluate the model’s performance through a series of experiments. The results demonstrated that our model achieved an F1 score of 86.54%, significantly outperforming existing methods. The contributions of this research are threefold: (1) We designed an efficient named entity recognition framework for marine domain texts, improving the recognition of long and nested entities. (2) By introducing the attention mechanism, we enhanced the model’s ability to recognize complex entity structures in coral reef ecosystem texts. (3) This work offers new tools and perspectives for marine domain knowledge graph construction and study, laying a foundation for future research. These advancements propel the development of marine domain text analysis technology and provide valuable references for related research fields.

Abstract The utilization of hot carriers as a means to surpass the Shockley‐Queasier limit represents a promising strategy for advancing highly efficient photovoltaic devices. Quantum dots, owing to their discrete energy states and limited multi‐phonon cooling process, are regarded as one of the most promising materials. However, in practical implementations, the presence of numerous defects and discontinuities in colloidal quantum dot (CQD) films significantly curtails the transport distance of hot carriers. In this study, the harnessing of excess energies from hot‐carriers is successfully demonstrated and a world‐record carrier diffusion length of 15 µm is observed for the first time in colloidal systems, surpassing existing hot‐carrier materials by more than tenfold. The observed phenomenon is attributed to the specifically designed honeycomb‐like topological structures in a HgTe CQD superlattice, with its long‐range periodicity confirmed by High‐Resolution Transmission Electron Microscopy(HR‐TEM), Selected Area Electron Diffraction(SAED) patterns, and low‐angle X‐ray diffraction (XRD). In such a superlattice, nonlocal hot carrier transport is supported by three unique physical properties: the wavelength‐independent responsivity, linear output characteristics and microsecond fast photoresponse. These findings underscore the potential of HgTe CQD superlattices as a feasible approach for efficient hot carrier collection, thereby paving the way for practical applications in highly sensitive photodetection and solar energy harvesting.

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

Abstract Background End‐stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). Aims We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet‐activating factor (PAF), and P‐selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function. Methods The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF. Results and Discussion The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP‐1, respectively (p

The aim of this study was to investigate the possible molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in Alzheimer's disease (AD). The active ingredients of SSF and their targets were identified via network pharmacology and bioinformatics analysis. To test the successful establishment of a rat model of AD by Aβ25-35 combined with RHTGF-β1 and AlCl3, the Morris water maze test was used. To intervene, three different doses of SSF were administered. The model group and the control group were included among the parallel groups. A shuttle box test, immunohistochemistry, an enzyme-linked immunosorbent assay, qPCR and Western blot were performed to verify the results. Based on the intersection of genes among AD disease targets, SSF component targets, and differentially expressed genes in the single cell dataset GSE138852 and bulk-seq dataset GSE5281, nine genes related to the action of SSF on AD were identified. SSF have an important anti-AD pathway in the cAMP signaling pathway. SSF can ameliorate the conditioned memory impairment, augment Brdu protein expression and cAMP content; and differentially regulate the mRNA and protein expressions of GPCR, Gαs, AC1, PKA, and VEGF. The cAMP-PKA-CREB pathway in the SSF may mediate the ability of the SSF to ameliorate the composite-induced memory loss and nerve regeneration in rats induced by composite Aβ.

Modern Chinese traditional instruments have also embarked on a path of learning from Western musicology. Most research on instrument improvement has focused solely on Western instruments and issues inherent to the instruments themselves. However, to explore further directions for the improvement of Chinese instruments and enhance the quality of instrument creation and performance, this paper employs grounded theory to construct a “Sound Performance—Subject Driving—Environmental Inducing” dynamic model (SSE) for the improvement of Chinese traditional instruments. This model analyzes the various factors and driving mechanisms influencing improvement. We found that sound optimization is the main force driving instrument improvement, exerting the greatest influence on the improvement process. In terms of external driving forces, professional knowledge and esthetic pursuit play a crucial role, forming a dynamic triangular relationship among instrument manufacturers, performers, and Chinese traditional music groups. The dynamic changes in instrument improvement, through this triangular interaction, are ultimately influenced by cultural recognition, social policy, and technological innovation.

Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are one of the most extensively researched stem cell types due to their potential for multi-lineage differentiation, secretion of regenerative factors, modulations of immunological activities, and the release of regenerative substances and influence immunological processes. Since UC-MSCs must be cultivated on a large scale for clinical use, selecting the appropriate storing passage, such as the usage-based passage of UC-MSCs, is critical for long-term autologous or allogeneic usage. Long-term cultivation of stem cells, on the other hand, causes them to lose their pluripotent differentiation capacity. As a result, distinguishing between high and low passages of UC-MSCs and identifying the particular variations associated with stem cells and their modes of action is essential for regenerative medicine. Therefore, we investigated the biological features and transcriptional changes of UC-MSCs over passages. Methods: UC-MSCs were isolated from the tissues of the human umbilical cord, and UC-MSCs from five passages (P1, P3, P5, P10 and P15) with three repetitions were compared and identified based on morphology, cell markers, differentiation capacity, and aging-related characteristics. It was previously assumed that the phenotype of cells before the P10 passage was stable, defined as early passage, and that culture could be continued until the 15th passage, defined as late passage. Next, the five passages of UC-MSCs were sequenced using high-throughput complete transcriptome sequencing. Fuzzy C-Means Clustering (FCM) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to find hub genes, and gene silencing was performed to investigate the impact of missing genes on the stemness of UC-MSC cells. Results: UC-MSCs of different passages displayed similar surface markers, including CD73, CD105, CD90, CD34, CD45 and HLA-DR. However, the proliferation time of late-phase UC-MSCs was longer than that of early-phase UC-MSCs, and the expression of the senescence-associated (SA)-β-gal staining marker was higher. At the same time, pluripotency markers (NANOG, OCT4, SOX2 and KIF4A) were down-regulated, and the multi-differentiation potential was reduced. Meanwhile, KIFC1 and UBE2C were down-regulated in late-phase UC-MSCs, which were involved in the maintenance of stemness. Conclusions: KIFC1 and UBE2C were highly expressed in early-UC-MSCs and showed a downward gradient trend with cell expansion in vitro. They regulated UC-MSC proliferation, colony sphere formation, multiple differentiation, stemness maintenance, and other biological manifestations. Therefore, they are anticipated to be new biomarkers for UC-MSCs quality identification in regenerative medicine applications.

In this study, we delved into the safety profile of alpelisib, an FDA-approved treatment for hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer, and PIK3CA-Related Overgrowth Spectrum (PROS). Despite its approval, real-world, long-term safety data is lacking. Our research scrutinizes the FDA database to assess alpelisib 's safety. We retrospectively analyzed data from April 2019 to June 2023 using four algorithms. Among 7,609,450 reports, 6692 implicated alpelisib as the primary suspected drug, uncovering adverse events (AEs) across 26 organ systems. Notably, we identified 21 previously unlisted AEs. Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.

As advances in artificial intelligence (AI) continue to transform and revolutionize the field of medicine, understanding the potential uses of generative AI in health care becomes increasingly important. Generative AI, including models such as generative adversarial networks and large language models, shows promise in transforming medical diagnostics, research, treatment planning, and patient care. However, these data-intensive systems pose new threats to protected health information. This Viewpoint paper aims to explore various categories of generative AI in health care, including medical diagnostics, drug discovery, virtual health assistants, medical research, and clinical decision support, while identifying security and privacy threats within each phase of the life cycle of such systems (ie, data collection, model development, and implementation phases). The objectives of this study were to analyze the current state of generative AI in health care, identify opportunities and privacy and security challenges posed by integrating these technologies into existing health care infrastructure, and propose strategies for mitigating security and privacy risks. This study highlights the importance of addressing the security and privacy threats associated with generative AI in health care to ensure the safe and effective use of these systems. The findings of this study can inform the development of future generative AI systems in health care and help health care organizations better understand the potential benefits and risks associated with these systems. By examining the use cases and benefits of generative AI across diverse domains within health care, this paper contributes to theoretical discussions surrounding AI ethics, security vulnerabilities, and data privacy regulations. In addition, this study provides practical insights for stakeholders looking to adopt generative AI solutions within their organizations.

Common tyrosinase (TYR) inhibitors used in cosmetics, such as hydroquinone, kojic acid, and arbutin, can cause side effects including erythema, skin peeling, and dryness. Therefore, the development of natural whitening agents that offer excellent permeability, minimal irritation, and high safety has become a primary focus in the field of TYR inhibitors. In this study, we demonstrate that White birch sap (WBS), within a safe concentration range, effectively reduces TYR activity and melanin content in both B16F10 mouse melanoma cells and zebrafish larvae. Importantly, WBS exhibits minimal irritation to neutrophils in fluorescent zebrafish and does not affect the behavior of adult zebrafish. Furthermore, WBS downregulates the gene expression levels of microphthalmia-associated transcription factor, TYR, tyrosinase-related protein-1, and tyrosinase-related protein-2 in B16F10 cells. In conclusion, our research confirms that WBS, a naturally derived substance, offers high safety and mild effects, making it a promising candidate for a skin-whitening agent.

Summary: DNA demethylase TET2 was related with lung function. However, the precise role of TET2 in cigarette smoke (CS)-induced apoptosis of airway epithelium cells, and the mechanisms involved, have yet to be elucidated. Here, we showed that CS decreased TET2 protein levels but had no significant effect on its mRNA levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients and CS-induced COPD mice model and even in airway epithelial cell lines. TET2 could inhibit CS-induced apoptosis of airway epithelial cell in vivo and in vitro. Moreover, we identified ubiquitin-specific protease 21 (USP21) as a deubiquitinase of TET2 in airway epithelial cells. USP21 interacted with TET2 and inhibited CSE-induced TET2 degradation. USP21 downregulated decreased TET2 abundance and further reduced the anti-apoptosis effect of TET2. Thus, we draw a conclusion that the USP21/TET2 axis is involved in CS-induced apoptosis of airway epithelial cells.

The capability of 5, 10, 15 mM γ-aminobutyric acid (GABA) to improve the postharvest quality and antioxidant system of strawberry was evaluated in this study. The application of GABA had no effect on fruit skin color and firmness. The weight loss in fruits treated with 10 mM GABA was significantly lower than the control. GABA treatments resulted in higher levels of total soluble sugar, titratable acid, SOD and CAT activities with 10 mM being the most significant effect. Specifically, 10 mM GABA significantly induced the accumulation of fructose, oxalic acid, and succinic acid. Besides, GABA application increased the content of total anthocyanins and total flavonoids, and DPPH radical scavenging activity in fruits. The GABA-treated fruits especially at 5 mM and 10 mM displayed less ROS and MDA. These data suggested that application of 10 mM GABA might be a promising strategy to improve the postharvest marketability of strawberry.

Background Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity.Conclusions Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.

ABSTRACT Staphylococcus aureus produces various hemolysins regulated by the Agr-QS system, except β-hemolysin encoded by the gene hlb. A classical laboratory S. aureus strain RN4220 displays only the β-hemolysin phenotype. It was suspected that the 8A mutation at the end of its agrA gene delayed the expressions of hla and RNAIII, then failed to express α- and δ-hemolysins. However, hla gene expression was detected at the later culture time without α-hemolysin phenotype, the reason for such a phenotype has not been clearly understood. We created hlb knockout and complementary mutants via homologous recombination in RN4220 and NRS049, two strains that normally produce β-hemolysin and carry agrA mutation. We found interestingly that the presence or absence of α-hemolysin phenotype in such strains depended on the expression of β-hemolysin instead of agrA mutations, which only inhibited δ-hemolysin expression. The hemolysis phenotype was verified by the Christie-Atkinson-Munch-Peterson (CAMP) test. Quantitative reverse transcription PCR was carried out to evaluate the relative gene expressions of hlb, hla, and RNAIII. The construction of mutants did not affect the agrA mutation status. We demonstrate that the absence of α-hemolysin in S. aureus RN4220 and NRS049 strains is attributed to their production of β-hemolysin instead of agrA mutation. Our findings broaden the understanding of the molecular mechanisms that control hemolysin expression in S. aureus that is crucial for the development of new therapeutic strategies to combat S. aureus infections.IMPORTANCEα-Hemolysin is a critical virulence factor in Staphylococcus aureus and its expression is largely controlled by the Agr-QS system. Nonetheless, the hemolysis phenotype and the regulation of the Agr-QS system in S. aureus still hold many mysteries. Our study finds that it is the expression of β- hemolysin rather than the agrA mutation that inhibits the function of the α-hemolysin in an important S. aureus strain RN4220 and a clinical strain presents a similar phenotype, which clarifies the misunderstood hemolytic phenotype and mechanism of S. aureus. Our findings highlight the interactions among different toxins and their biological roles, combined with QS system regulation, which is ultimately the true underlying cause of its virulence. This emphasizes the importance of considering the collaborative action of various factors in the infection process caused by this significant human pathogen.

ObjectiveThe aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection.MethodsThis retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months.ResultsA total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = −0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871–10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071–4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563–7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621–396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029–3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190–27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074–10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months.ConclusionIn SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.