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Abstract Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS–MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS–MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013–1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004–1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641–0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.

Abstract As frontline cells, the precise recruitment of neutrophils is crucial for resolving inflammation and maintaining the homeostasis of the organism. Increasing evidence suggests the pivotal role of neutrophil chemotaxis in cancer progression and metastasis. Here, we collected clinical data and peripheral blood samples from patients with tumours to examine the alterations in the neutrophil quantity and chemotactic function using the Cell Chemotaxis Analysis Platform (CCAP). Transcriptome sequencing data of pan-cancer were obtained from The Cancer Genome Atlas (TCGA). Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, we selected a total of 29 genes from 155 neutrophil- and chemotaxis-related genes to construct the ChemoScore model. Meanwhile, nomogram-based comprehensive model was established for clinical application. Furthermore, immunofluorescence (IF) staining was employed to assess the relationship between the neutrophils infiltrating and the survival outcomes of tumours. In this observational study, the chemotactic function of neutrophils was notably diminished in patients. The establishment and validation of ChemoScore suggested neutrophil chemotaxis to be a risk factor in most tumours, whereby higher scores were associated with poorer survival outcomes and were correlated with various immune cells and malignant biological processes. Moreover, IF staining of tumour tissue substantiated the adverse correlation between neutrophil infiltration and the survival of patients with lung adenocarcinoma (P = 0.0002) and colon adenocarcinoma (P = 0.0472). Taken together, patients with tumours demonstrated a decrease in chemotactic function. ChemoScore potentially prognosticates the survival of patients with tumours. Neutrophil chemotaxis provides novel directions and theoretical foundations for anti-tumour treatment.

Abstract Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.

Xinyang Nie,1– 3,* Jian Liu,1,2,* Daohan Wang,1,2,* Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Abstract Objective Using Optical coherence tomography (OCT), we evaluated the association between peripapillary retinal nerve fiber, macular thickness, macular ganglion cell‐inner plexiform layer, and drug resistance. Methods In this cross‐sectional study, we recruited people diagnosed with epilepsy and healthy controls. People with epilepsy were further stratified as drug‐resistant or non‐drug‐resistant based on their response to anti‐seizure medications. OCT measurements were conducted, and findings in right eye were analyzed. Results Fifty‐one drug‐resistant participants, 37 non‐drug‐resistant, and 45 controls were enrolled. The average peripapillary retinal nerve fiber layer, ganglion cell‐inner plexiform layer, and macular thickness were thinner in the epilepsy groups than in controls. The drug‐resistant group had significantly lower average ganglion cell‐inner plexiform layer thickness (p = 0.004) and a higher proportion of abnormal/borderline GC/IPL thickness (p = 5.40E‐04) than the non‐drug‐resistant group. Nevertheless, no significant differences were seen between the average thickness of peripapillary retinal nerve fiber and macular thickness. The temporal sectors of these three parameters were also significantly thinner in the drug‐resistant group than in the non‐drug‐resistant. In a multivariate regression model, drug resistance was an independent predictor of reduced ganglion cell‐inner plexiform thickness (Odds ratios OR = 10.25, 95% CI 2.82 to 37.28). Increased seizure frequency (r = −0.23, p = 0.039) and a higher number of anti‐seizure medications ever used (r = −0.27, p = 0.013) were negatively associated with ganglion cell‐inner plexiform layer thickness. Significance Individuals with drug‐resistant epilepsy had a consistent reduction in average ganglion cell‐inner plexiform layer thickness and the temporal sector of peripapillary retinal nerve fiber layer and macular thickness. This suggests that ganglion cell‐inner plexiform layer thickness could potentially serve as an indicator of the burden of drug resistance, as it correlated with reduced thickness in individuals having more frequent seizures and greater exposure to ASMs. Plain Language Summary In our study, we used a special tool called OCT to measure how thick the retina is in people with epilepsy and in healthy control. We found that the retina was consistently thinner in all areas for those with epilepsy compared to healthy control. Particularly, a specific layer called the ganglion cell‐inner plexiform layer was a lot thinner in the group that didn't respond to medications, and this thinning was related to how often seizures occurred and how much medications were taken. Also, certain parts of the retina were thinner in the drug‐resistant group.

Abstract The deep learning (DL)-based prediction of accurate lymph node (LN) clinical target volumes (CTVs) for nasopharyngeal carcinoma (NPC) radiotherapy (RT) remains challenging. One of the main reasons is the variability of contours despite standardization processes by expert guidelines in combination with scarce data sharing in the community. Therefore, we retrospectively generated a 262-subjects dataset from four centers to develop the DL models for LN CTVs delineation. This dataset included 440 computed tomography images from different scanning phases, disease stages and treatment strategies. Three clinical expert boards, each comprising two experts (totalling six experts), manually delineated six basic LN CTVs on separate cohorts as the ground truth according to LN involvement and clinical requirements. Several state-of-the-art segmentation algorithms were evaluated on this benchmark, showing promising results for LN CTV segmentation. In conclusion, this work built a multicenter LN CTV segmentation dataset, which may be the first dataset for automatic LN CTV delineation development and evaluation, serving as a benchmark for future research.

Abstract Green and sustainable development is unstoppable. The digital economy has driven great changes in production methods and has become a key strength in reshaping global economic structure and achieving sustainable development. Cities are both the mainstay of economic growth and the main source of various environmental pollution problems. Therefore, studying the relationship between urban digital economy and urban green total factor productivity is of great significance. Based on panel data from 252 cities in China 2011–2019, a two-way fixed effects model was used to examine the impact of urban digital economy on urban green total factor productivity. The empirical results indicate that: (1) Urban digital economy has a significant positive impact on urban green total factor productivity. (2) Urban technological-innovation-level and human-capital-structure of play a mediating role in the impact. (3) This impact has regional heterogeneity and resource-based type heterogeneity. The research conclusions are not only valuable supplements to previous research, but also providing reliable instructions for implementing a flexible digital economy policy.

Abstract Background Olezarsen is a GalNAc3-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans. Methods A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively. Results There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III/TG was − 39.4%/ − 17.8%, − 60.8%/ − 52.7%, and − 68.1%/ − 39.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III/TG was − 81.6/ − 73.8% vs − 17.2/ − 40.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C. Conclusions Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.

Abstract Background There are no standard treatment options for bilateral multiple pulmonary nodules requiring resection. This study aimed to summarize the experience of simultaneous bilateral uniportal video-assisted thoracoscopic surgery for the treatment of bilateral multiple primary pulmonary nodules. Methods The clinical data of 65 cases of simultaneous bilateral uniportal thoracoscopic surgery for bilateral multiple primary pulmonary nodules treated were retrospectively analyzed. These cases were treated within The Ninth Medical Center of PLA General Hospital between January 2018 and November 2020. Parameters related to the surgery, perioperative aspects, surgical techniques, pathology results, and postoperative complications were examined. Results All surgeries were conducted through uniportal video-assisted thoracoscopic surgery, with no instances of intraoperative conversion to thoracotomy. Fifty-three patients further underwent CT-guided Hookwire localization for the localization of pulmonary nodules. A total of 189 nodules were resected using multiple surgical procedures, with a malignancy rate of 86.2%. The average operation time was 226 ± 77.4 min, the average thoracic drainage duration was 3.1 ± 1.5 days, the average 24 h pleural drainage was 385.9 ± 157.4 mL, the average postoperative hospital stay was 8.6 ± 2.4 days, and the average blood loss was 77.2 ± 33.8 mL. Post-surgery, all patients were transferred to the ward safely within 12 h. 15.38% of patients have prolonged drainage time, and 12.31% of patients experience complications such as lung infection, arrhythmia, and venous thrombosis. Conclusion The selected cases undergoing simultaneous bilateral uniportal video-assisted thoracoscopic surgery for the management of bilateral multiple primary pulmonary nodules demonstrated favorable outcomes. Our observations indicate the safety and feasibility of this procedure, providing an individualized and precise treatment approach for affected patients.

Yongcheng Yao,1,2 Jie Tang,3 Zhenzhen Li,1 Shuyan Chen,1 Haixia Du,1 Lingeng Lu4 1School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, People’s Republic of China; 2WorldPop, School of Geography and Environmental Science, University of Southampton, Southampton, UK; 3Library, Zhengzhou University of Technology, Zhengzhou, Henan, People’s Republic of China; 4Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, New Haven, CT, USACorrespondence: Yongcheng Yao, School of Mathematics and Statistics, Zhengzhou Normal University, Zhengzhou, Henan, 450044, People’s Republic of China, Email 806306944@qq.comObjective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China.Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health.Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P

Abstract Aims This study aims to explore the molecular mechanism of circular RNAs' (circRNAs) potential involvement in myocardial ischaemia–reperfusion injury (MIRI). Methods and results Differently expressed genes in myocardial infarction (MI) were identified by screening the GEO database. Serum was collected from MI patients and healthy volunteers (n = 5 for each group). AC16 cells were cultured and exposed to hypoxia/reperfusion (H/R) treatment for the cell experiments. Then candidate genes were validated in human serum and the H/R model. Quantitative real‐time PCR and western blot were used to detect expression of key molecules such as circDGKZ, miR‐345‐5p, and Toll‐like receptor 4 (TLR4), as well as pyroptosis markers such as NOD‐like receptor thermal protein domain‐associated protein 3 (NLRP3), ASC, C‐caspase1, interleukin (IL)‐1β, and IL‐18. CircDGKZ was positively correlated in human serum (P

With the economic development and people's needs, China's dairy industry has developed rapidly. China has become one of the largest dairy markets in the world. As a core backbone course of dairy major, the Dairy Technology course has to carry out ideological and political education when the state advocates to start the new engineering construction and ideological and political education. Taking the ideological and political education in Dairy Technology course of Northeast Agricultural University for example, this paper introduces the design ideas and specific teaching reform content of ideological and political education. It also provides a reference for ideological and political education construction in dairy related majors courses.

Background and objective: Stress urinary incontinence (SUI) in women is a common condition that affects middle-aged and elderly women. Currently, there are still many limitations in the epidemiological research on SUI. This study aims to address the gap in the prevalence of female SUI in mainland China and provide theoretical support for the prevention and treatment of SUI. Methods: A comprehensive literature search was conducted on the prevalence of female SUI in mainland China, systematically searching Chinese and English databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Weipu Database as of April 1, 2024. Detailed criteria for screening and exclusion were established. The prevalence of SUI in the selected studies was synthesized using Stata MP (version 15) software, and a multisubgroup analysis, a sensitivity analysis, and publication bias detection of the prevalence of SUI were also performed using the software. Additionally, ArcGIS software (version 10.8) and Geoda software (version 1.2) were utilized to explore the geographical distribution characteristics of the prevalence of female SUI in mainland China. Key findings and limitations: A total of 688 articles were screened, and finally 85 articles were included. The overall rate of female SUI in mainland China was 24.5% (95% confidence interval: 22.5–26.5%). The heterogeneity of the study is statistically significant (I2 = 99.0%, p

Background: O-GlcNAc transferase (OGT) is responsible for attaching O-linked N-acetylglucosamine (O-GlcNAc) to proteins, regulating diverse cellular processes ranging from transcription and translation to signaling and metabolism. This study focuses on the role and mechanisms of OGT in osteogenesis. Materials and methods: We found that OGT is downregulated in osteoporosis by bioinformatics analysis, determined its role in osteogenic differentiation by using OGT inhibitors (or OGA inhibitors) as well as conditional knockout OGT mice in vitro and in vivo, and explored and specific mechanisms by quantitative proteomic analysis and RNA-seq, qRT-PCR, western blotting, immunofluorescence, H&E, ALP, ARS, Masson staining, IHC, micro CT, etc. Results: we revealed that OGT positively influenced osteogenesis and osteoblast differentiation in vitro as well as ovariectomy (OVX) mice in vivo. Consistently, mice with conditionally depleted OGT exhibited a reduction in bone mass, while O-GlcNAcylation enhancer could partially recover bone mass in ovariectomy (OVX) mice. Mechanistically, quantitative proteomic analysis and high-throughput RNAseq further reveals that HDAC5 is one of the endogenous O-GlcNAcylation substrates, and O-GlcNAcylation of HDAC5 on Thr934 promotes its translocation to lysosomes and subsequent degradation, thus, elevating the O-GlcNAcylation level of HDAC5 leads to its cytoplasmic cleavage, consequently diminished its nuclear entry and enhanced DNA transcription. The OGT-mediated O-GlcNAcylation of HDAC5 modulates the balance between its cytoplasmic proteolysis and nuclear entry, thereby impacting the Notch signaling pathway and DNA epigenetic modifications then playing a role in osteogenesis. Conclusion: OGT is a regulator that promotes osteoblast differentiation and bone regeneration. Additionally, it highlights the critical function of HDAC5 O-GlcNAcylation in controlling epigenetics. This study offers fresh perspectives on osteogenesis and O-GlcNAcylation, proposing that the OGT-mediated O-GlcNAcylation of HDAC5 could be a promising target for osteoporosis treatment. The translational potential of this article: On one side, OGT might potentially be used as a new biomarker for clinical diagnosis of osteoporosis (OP) in the future. On the other side, small molecule inhibitors of HDAC5, a glycosylation substrate of OGT, or OGT agonists such as silymarin, could all potentially serve as therapeutic targets for the prevention or treatment of OP in the future.

Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of Botrytis cinerea, which suffers from limited availability of genetic engineering tools. Here, Yarrowia lipolytica was engineered to enable de novo biosynthesis of ABA. To overcome the rate-limiting P450 enzymes, systematic engineering strategies were implemented. Firstly, the dissolved oxygen was increased to boost the activity of P450 enzymes. Secondly, the expansion of endoplasmic reticulum was implemented to improve the functional expression of P450 enzymes. Lastly, rate-limiting enzymes were assembled to facilitate substrate trafficking. Moreover, ABA production was further improved by strengthening the mevalonate pathway. Finally, the engineered strain produced 1221.45 mg/L of ABA in a 5-L bioreactor. The study provides effective approaches for alleviating rate-limiting P450 enzymes to enhance ABA production and achieve competitive industrial-level ABA production in Y. lipolytica.

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

To summarize the nursing experience of a 4-month-old critical ill child with perianal necrotizing fasciitis complicated with severe sepsis, refractory septic shock and respiratory failure. The key points of nursing include: Timely assessment of wounds and wound conditions; Strengthening wound care and promote wound healing; Strengthening perianal and perineal nursing to prevent infection; ensuring the safety of the child and avoiding the pressure of the stoma and the wound; Attention should be paid to the use of sedative and analgesic drugs in children, and analgesic evaluation should be strengthened to reduce pain in children. After 24 days of careful care, the child's condition was stable. The wound had healed well, and the child had been transferred to the general ward for continued treatment. (本文总结1例肛周坏死性筋膜炎(NF)危重症患儿的护理经验。护理要点包括: 及时评估伤口和创面的情况, 调整伤口护理措施; 加强伤口护理, 促进伤口愈合; 加强肛周、会阴护理预防感染; 积极变换体位, 避免造口及创面受压; 科学使用儿童镇静镇痛药物, 加强镇痛评估, 减轻患儿疼痛。经过24 d的精心治疗和护理, 患儿病情稳定, 伤口愈合良好, 转往普通病房继续治疗。)

【Objective】The study was conducted to analyze the effects of single and mixed fermentation of Dendrocalamus latiflorus with Lactiplantibacillus plantarum and Limosilactobacillus fermentum on their quality, to explore suitable fermentation agents for D. latiflorus.【Method】L. plantarum S1 and L. fermentum G9 were used as fermentation strains to study the effects of single and mixed fermentation of the two Lactobacillus strains on the lactic acid bacteria count, reducing sugars, pH values, total acids, nitrites, antioxidants, organic acids, biogenic amines and volatile compounds of fermented D. latiflorus.【Result】Compared with the natural fermentation group, fermentation with L. plantarum S1 and L. fermentum G9 significantly increased the lactic acid bacteria count, total acids, organic acids and antioxidant activity (P < 0.05) of fermented D. latiflorus, while its pH value and reducing sugar content were reduced. At the 4th day of fermentation, the lactobacillus count in G9 fermentation group was the highest, 8.70 lg (CFU/mL), and at the end of fermentation, the lactobacillus count in inoculated fermentation group was higher than 6.31 lg (CFU/mL), which was significantly higher than that in natural fermentation group. Moreover, the inoculated fermentation groups showed higher total acids and lactic acid contents in comparison with the naturally fermented D. latiflorus. The highest total acid (5.86 g/kg) and lactic acid content (3.66 g/kg) were both found in S1 fermentation group. In addition, inoculated fermentation with lactic acid bacteria could effectively reduce the nitrite and biogenic amine contents of fermented D. latiflorus, and the nitrite and biogenic amine contents of inoculated fermentation groups were significantly lower than those of natural fermentation group during the fermentation. The results of volatile flavor substances analysis showed that 26, 33, 29 and 31 compounds were detected in the natural, S1, G9 and mixed fermentation groups with the relative contents of 12.75, 22.58, 15.15 and 20.81 mg/kg, respectively. Compared with the inoculated fermentation group, the natural fermentation group had relatively fewer types of volatile substances, and the relative content of volatile substances (12.75 mg/kg) was lower than that of other fermentation groups.It was shown that inoculated fermentation could effectively enhance the types and relative contents of volatile flavor substances in fermented D. latiflorus.【Conclusion】The above findings indicated that both L. plantarum S1 and L. fermentum G9 could better enhance the quality and flavor of fermented D. latiflorus, which could be used as potential fermentation agents for D. latiflorus.

Abstract Background It is difficult to detect the outbreak of emergency infectious disease based on the exiting surveillance system. Here we investigate the utility of the Baidu Search Index, an indicator of how large of a keyword is in Baidu’s search volume, in the early warning and predicting the epidemic trend of COVID-19. Methods The daily number of cases and the Baidu Search Index of 8 keywords (weighted by population) from December 1, 2019 to March 15, 2020 were collected and analyzed with times series and Spearman correlation with different time lag. To predict the daily number of COVID-19 cases using the Baidu Search Index, Zero-inflated negative binomial regression was used in phase 1 and negative binomial regression model was used in phase 2 and phase 3 based on the characteristic of independent variable. Results The Baidu Search Index of all keywords in Wuhan was significantly higher than Hubei (excluded Wuhan) and China (excluded Hubei). Before the causative pathogen was identified, the search volume of “Influenza” and “Pneumonia” in Wuhan increased with the number of new onset cases, their correlation coefficient was 0.69 and 0.59, respectively. After the pathogen was public but before COVID-19 was classified as a notifiable disease, the search volume of “SARS”, “Pneumonia”, “Coronavirus” in all study areas increased with the number of new onset cases with the correlation coefficient was 0.69 ~ 0.89, while “Influenza” changed to negative correlated (rs: -0.56 ~ -0.64). After COVID-19 was closely monitored, the Baidu Search Index of “COVID-19”, “Pneumonia”, “Coronavirus”, “SARS” and “Mask” could predict the epidemic trend with 15 days, 5 days and 6 days lead time, respectively in Wuhan, Hubei (excluded Wuhan) and China (excluded Hubei). The predicted number of cases would increase 1.84 and 4.81 folds, respectively than the actual number of cases in Wuhan and Hubei (excluded Wuhan) from 21 January to 9 February. Conclusion The Baidu Search Index could be used in the early warning and predicting the epidemic trend of COVID-19, but the search keywords changed in different period. Considering the time lag from onset to diagnosis, especially in the areas with medical resources shortage, internet search data can be a highly effective supplement of the existing surveillance system.

Abstract The individuals often show consolation to distressed companions or show aggression to the intruders. The circuit mechanisms underlying switching between consolation and aggression remain unclear. In the present study, using male mandarin voles, we identified that two distinct subtypes of oxytocin receptor (OXTR) neurons in the medial amygdala (MeA) projecting to the anterior insula (AI) and ventrolateral aspect of ventromedial hypothalamus (VMHvl) response differently to stressed siblings or unfamiliar intruders using c-Fos or calcium recording. Oxytocin release and activities of PVN neurons projecting to MeA increased upon consoling and attacking. OXTR antagonist injection to the MeA reduced consoling and attacking. Apoptosis, optogenetic or pharmacogenetic manipulation of these two populations of neurons altered behavioral responses to these two social stimuli respectively. Here, we show that two subtypes of OXTR neurons in the MeA projecting to the AI or VMHvl causally control consolation or aggression that may underlie switch between consolation and aggression.

Abstract Background Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. β-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. Results BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. Conclusions These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii–ILA–AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract Graphical Abstract

Abstract Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure. Overall, E. japonicus peptides showed better results than G. max peptides in treating CDI. This study supports the potential treatment of CDI with natural peptides and promotes the development of specialty foods for CDI enteritis. Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure.

Aiming at the problem of large deformation and instability control of narrow coal pillar in the vertical stratification section of extra-thick coal seam, the stability and control technology of the surrounding rock of narrow coal pillar in extra-thick coal seam are studied by combining theoretical analysis, numerical simulation and field test. Based on the calculation of the triaxial stress in the narrow coal pillar, the yield criterion of the plane strain of the narrow coal pillar is obtained based on the Mohr-Coulomb failure strength, the failure characteristics and the evolution law of the damage degree of the narrow coal pillar are qualitatively analyzed, and the instability mechanism and size effect of the narrow coal pillar are further analyzed. Finally, the key technologies of surrounding rock control of the narrow coal pillar are given. It is verified by numerical simulation and field test. The research results show that ① The damage degree of the middle part of the narrow coal pillar is greater than that of the two sides, and the damage degree of the middle part from the top to the bottom develops from serious to slight. With the increase of width-height ratio, the damage degree and the proportion of serious damage area in the narrow coal pillar gradually decrease. When the width-height ratio is greater than 1∶1, a large range of slight damage area begins to appear in the middle and lower part of the narrow coal pillar. When the width-height ratio is greater than 5∶3, the proportion of slight damage area exceeds 50%. When C≥3 MPa, or φ≥20°, the damage degree of the two sides of the narrow coal pillar becomes slight. ② The side of the mining roadway in the working face is a low-stress bearing area of the narrow coal pillar. Under the action of high stress in the upper part, the coal body in the large-scale low-stress bearing area moves to the roadway, resulting in a continuous large deformation of the two sides, which in turn affects the stability of the roof. The height of coal pillar is the main controlling factor for the stability of the narrow coal pillar in the middle and bottom layered sections. The increase of width-height ratio of the narrow coal pillar has little influence on the bearing strength of high strength bearing area, while the bearing strength of low strength bearing area increases obviously. Reasonable width-height ratio of the narrow coal pillar can balance the proportion of high and low strength bearing area in coal pillar. ③ The stability of surrounding rock should be considered in the design of layered narrow coal pillars when both sides of the working face are mined out, so as to ensure that the range of high-strength bearing area inside the coal pillar is greater than half of the width and height of the coal pillar. Through the joint strengthening support measures, multiple joint control areas from shallow to deep are formed in the coal pillar to jointly maintain the self-stability of the coal pillar.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

Abstract Purpose To explore the effects of a single dose of uridine adenosine tetraphosphate (Up4A) administered through the tail vein, on the blood pressure of mice. Methods The mice were separated into three groups: the Up4A group, the norepinephrine (NA) group, and the α, β-methylene adenosine triphosphate (α, β-meATP) group. Each group of mice were injected drugs through the tail vein at 1, 3, 10, and 30 nmol/kg doses in an ascending order. Additionally, six mice were injected Up4A through the tail vein at 20, 40, 60, and 80 nmol/kg doses in an ascending order. The administration intervals for each dose were 20 min. Results Mice in these groups experienced a rapid increase in blood pressure, reaching its peak within 10 s after drug administration. It took approximately 120 s for the blood pressure to return to baseline levels after the administration of the drugs in both the NA and α, β-meATP groups. After higher doses of Up4A were administered to the mice, their blood pressure exhibited biphasic changes. Initially, blood pressure of the mice rapidly dropped to a minimum within 10 s, then rose rapidly to a peak within 30 s. Subsequently, it gradually declined, taking around 10 min to return to the levels before the drug administration. Conclusion Compared to NA and α, β-meATP, Up4A, which contains purine and pyrimidine components, displayed a weaker blood pressure-elevating potency. Through its corresponding structure, Up4A exerted vasodilatory and vasoconstrictive effects throughout the entire experiment resulting in biphasic changes in blood pressure.

Abstract Objective This study aims to examine the impact of nurses’ nursing information competence on their creative self-efficacy and innovation behavior, and to investigate its role as a mediating factor between these two elements. Methods A survey was conducted from July to September 2023 involving 1,200 nurses from two tertiary-level oncology specialty hospitals in Beijing, selected through convenience sampling. Instruments used included the Creative Self-Efficacy Scale, Nursing Information Competence Assessment Scale, and Nurses’ Innovative Behavior Scale. Data analysis was conducted using SPSS 25.0 and R 4.1.2; AMOS26 was used to construct structural equation models and Bootstrap method was used to test the mediating hypotheses. Results Out of the distributed questionnaires, 1,166 were valid, yielding an effective response rate of 97.16%. Pearson correlation analysis revealed significant correlations between innovation self-efficacy, nursing information competence, and nurses’ innovative behaviors (P

Abstract Background Larch is an important timber tree species. The traditional methods of tree genetic breeding have been progressing slowly. It is necessary to carry out gene function analysis and genetically modified breeding research. The NAC transcription factor family is a plant-specific transcription factor family with various biological functions, as shown in recent research. However, there are few studies on the NAC gene among gymnosperm coniferous species. Results LoNAC3 with complete cds was identified and isolated from the cDNA of Larix olgensis based on transcriptome data. The cDNA length of LoNAC3 is 1185 bp, encoding 394 amino acids, with a conserved NAM domain located at the N-terminus, and subcellular localization in the nucleus. The results of real-time quantitative PCR analysis showed that at different growth stages and in different tissues of L. olgensis, the relative expression level of LoNAC3 was highest in the needles. After drought, salt, alkali stress and hormone treatment, expression was induced to different degrees. The expression level of LoNAC3 was significantly increased under drought and salt conditions. The relative expression level changed under methyl jasmonate (MeJA) and abscisic acid (ABA) treatment. By observing the phenotype of overexpressed LoNAC3 tobacco, it was found that overexpressed tobacco is shorter and blooms earlier than wild-type tobacco. Under abiotic stress, LoNAC3 overexpressed tobacco has lower germination rates and poorer growth status. Transgenic tobacco under stress treatment has a higher malondialdehyde (MDA) content than wild-type tobacco, while peroxidase (POD) activity is lower than wild-type tobacco. Conclusions Through the analysis of LoNAC3 sequence and promoter expression, it can be concluded that LoNAC3 is involved in the drought and salt stress response processes of L. olgensis, and is induced by ABA and MeJA expression. Overexpression of LoNAC3 leads to stunted tobacco growth and negatively regulates its tolerance to drought and salt stress through the reactive oxygen species pathway. The preliminary analysis of the expression pattern and function of the LoNAC3 can provide a theoretical basis and high-quality materials for genetic improvement of larch in later stages.

Abstract Background Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors. Methods Data were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system. Results The total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60–74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38–5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82–7.58, RORadj = 7.10, 95%CI, 6.16–8.18, additive models = 2.0525, multiplicative models = 1.1622), metabolism and nutrition disorders (RORcrude = 3.27, 95%CI, 2.90–3.69, RORadj = 2.66, 95%CI, 2.30–3.08, additive models = 0.6194), and skin and subcutaneous tissue disorders (RORcrude = 1.41, 95%CI, 1.26–1.58, RORadj = 1.53, 95%CI, 1.34–1.75, additive models = 0.6927, multiplicative models = 5.3599). Subset data analysis showed that programmed death-1 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders; hepatobiliary disorders; and skin and subcutaneous tissue disorders. Programmed death ligand-1 combined with proton pump inhibitors was associated with adverse reactions of metabolism and nutrition disorders. Cytotoxic T-lymphocyte antigen-4 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders, and skin and subcutaneous tissue disorders. Conclusions Based on real-world data, four Standardized MedDRA Query System Organ Class toxicities were identified as drug-drug interactions associated with combining immune checkpoint and proton pump inhibitors. Clinicians should be cautious when administering these drugs concomitantly. Preclinical trials and robust clinical studies are required to explore the mechanisms and relationships underlying interactions, thus improving understanding of drug-drug interactions associated with this combination therapy.