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Abstract During non-rapid eye movement (NREM) sleep, neural ensembles in the entorhinal-hippocampal circuit responsible for encoding recent memories undergo reactivation to facilitate the process of memory consolidation. This reactivation is widely acknowledged as pivotal for the formation of stable memory and its impairment is closely associated with memory dysfunction. To date, the neural mechanisms driving the reactivation of neural ensembles during NREM sleep remain poorly understood. Here, we show that the neural ensembles in the medial entorhinal cortex (MEC) that encode spatial experiences exhibit reactivation during NREM sleep. Notably, this reactivation consistently coincides with isolated theta waves. In addition, we found that the nucleus reuniens (RE) in the midline thalamus exhibits typical theta waves during NREM sleep, which are highly synchronized with those occurring in the MEC in male mice. Closed-loop optogenetic inhibition of the RE-MEC pathway specifically suppressed these isolated theta waves, resulting in impaired reactivation and compromised memory consolidation following a spatial memory task in male mice. The findings suggest that theta waves originating from the ventral midline thalamus play a role in initiating memory reactivation and consolidation during sleep.

Abstract This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up.

Abstract Introduction Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. Methods We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. Results In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. Conclusion These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

ObjectiveTo provide a longitudinal evaluation tool based on the frequency of aggressive behavior for the aggression assessment of schizophrenia patients.MethodsThe Life History of Aggression was translated and revised to form the Life History of Aggression-Chinese Version （LHA-CV） based on 369 patients diagnosed with schizophrenia in the Chengdu community and compulsory medical institution. The reliability of LHA-CV was analyzed by means of split-half reliability, test-retest reliability and inter-evaluator consistency. The validity was analyzed by item analysis, construct validity and criterion validity.ResultsItem analysis found that LHA-CV had good homogeneity and discriminant validity. Exploratory factor analysis found that the Kaiser-Meyer-Olkin （KMO） test value was 0.80, and the Bartlett’s sphericity test χ2=1 203.46 （P

Abstract Background The purpose of this study was to explore the job burnout of primary healthcare workers in Guangzhou during the prevention and control of COVID-19 epidemic and its influencing factors from the perspective of institutional operation and management in 2021–2022. Methods A cross-sectional study involved 866 primary healthcare workers from different districts of Guangzhou, China. The Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS) was utilized to assess job burnout. From the perspective of organizational operation and management, the possible causes of job burnout among primary healthcare workers during COVID-19 have been categorized into 7 major aspects. Univariate and multivariate logistic regression analyses were conducted to identify influencing factors for job burnout in primary healthcare workers. Results The detection rate of job burnout among primary healthcare workers was 78.29%. Men (OR = 2.39) and whose institution was located in urban–rural fringe (OR = 1.56) were more likely to detect job burnout. Conversely, institution heads showed a lower risk of job burnout. From the perspective of institutional operation and management, workers who were not satisfied with personnel management (OR = 2.41), materials and vehicles (OR = 2.89), subsidies and compensation (OR = 2.18), humanistic care (OR = 2.11), superior management (OR = 8.32) were found to have a higher risk of job burnout. Conclusion The detection rate of job burnout among primary healthcare workers in Guangzhou was relatively high during the period of COVID-19. When there is another sudden major epidemic, the managers of institutions can focus on and deal with the problems related to the operation and management of institutions such as personnel management, materials and vehicles, subsidies and compensation, humanistic care, and superior management, so as to provide logistical support for the workers and alleviate their job burnout.

Background: Lactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation's role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens. Methods: Using TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens. Results: We identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels. Conclusions: Lactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.

BackgroundPrimary healthcare workers in China were vital in controlling COVID-19, facing unprecedented challenges due to the pandemic’s suddenness and transmissibility. This paper analyzed their work in Guangzhou, highlighting key difficulties in past epidemic control efforts.MethodsSemi-structured qualitative interviews were conducted with selected primary healthcare workers in Guangzhou City and audio-recorded until saturation of themes was reached. The data were analyzed independently for themes using NVivo V.12.ResultsThematic analysis of qualitative interview data revealed that challenges and difficulties encountered in grassroots epidemic prevention and control work during the COVID-19 pandemic were primarily categorized into seven dimensions: human resource allocation, material and vehicle support, epidemic prevention subsidies and compensation, humanistic care, upper-level management, horizontal collaboration, and resident cooperation.ConclusionBased on the findings, the research team recommends that administrative departments and institutions related to primary healthcare should appropriately schedule personnel work and rest time, adjust work content flexibly, optimize the allocation of medical and logistical resources, and increase investment in primary healthcare work as well as staff protection.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

Abstract PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.

Abstract94% of Fortune 1000 firms experienced supply chain disruptions. The severe shortage of essential medical supplies caused by COVID-19 has severely hampered the healthcare supply chain (HCSC). This study explores the impact of supply chain resilience (SCR) on supply chain performance (SCP) and the impact of communication (COM), organization culture (OC), top management support (TMS), and product complexity (PC) on SCR. The establishment of a theoretical framework is the goal of this study. This paper adopts mixed research methodologies: the qualitative method using semi-structured interviews and NVivo data analysis, and the quantitative method based on self-administered questionnaires and SmartPLS analysis. The study investigated SCR in the Chinese healthcare industry from the perspective of CAS (complex adaptive systems). 32 Tier-4 healthcare organizations from China took part in the interviews. 162 businesses filled out questionnaires to gather data from Chinese healthcare suppliers or manufacturers. The results suggested that SCR positively impacts SCP, and COM, OC, and PC positively impact SCR, but empirical evidence for the significance of TMS on SCR is still lacking. Top management in China’s healthcare sector still needs to improve SCR management, especially by incorporating digital technology into the direction of the company’s supply chain, including supply chain innovation brought about by new technology and big data analysis. This study can be expanded to include Chinese healthcare. In response to supply chain disruptions, this effort will improve SCR.

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

This paper investigates the chaotic synchronization of neural networks via sampled-data control with actuator saturation. First, a new generalized looped-functional is constructed by considering valid information from $t_{k}$ to t and from t to $t_{k+1}$ . Then, local stability conditions for the synchronization error system are given based on the Lyapunov stability theory. A sampled-data controller is designed to achieve the synchronization of the driving neural network and the response neural network by solving the convex optimization problem with given conditions. The proposed method’s effectiveness and practicality are numerically verified.

Abstract Background Declined skeletal muscle mass and function are inevitable consequences of long‐term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia. Methods Wild‐type and STINGgt/gt C57BL/6J mice and C2C12 myotubes were used to study the role of STING in the regulation of diabetic sarcopenia and the underlying mechanisms. Results STING was abnormally activated in diabetic muscles and in PA‐treated myotubes (P

Abstract Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method — multiple genetic abnormality sequencing (MGA-Seq) — to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA’s transcriptional regulatory function.

Abstract Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21 −/−) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21 −/− and Ctsk-cre; Trim21 f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

Levodopa is the mainstay of treatments for Parkinson’s disease (PD), but large heterogeneity exists in patient response. Increasing evidence implicates bile acids (BAs) involved in the pathogenesis of PD. Furthermore, BAs have also participated in drug bioavailability. However, the impact of BAs on levodopa response (LR) has not been investigated. This study evaluated the association between fecal BAs and LR. Levodopa challenge test (LCT) was conducted in 92 PD patients to assess LR. A total of 36 fecal BAs and plasma levodopa concentrations were detected using LC-MS/MS. The difference of BAs between subgroups with bottom and top 30% LR were analyzed and fecal samples from the two groups were collected for metagenomic shotgun analysis. No fecal BAs were significantly correlated with LR, except for chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3-β-glucuronide, R = −0.228, p-value = 0.039). We found no significant difference in BAs between subgroups with bottom and top 30% LR. What is more, no significant changes in bacterial species composition related to bile acids metabolism or in the proportional representation of genes encoding known bile acids enzymes were observed between the groups. Overall, our data do not support an association between fecal BAs and levodopa response in PD patients. More precise macro-metabolomic approaches are needed to reveal the potential association between gut microbial interactions and the treatment effect of levodopa.

During the fermentation of ripened pu-erh tea (RPT), the composition of lipids and other compounds changes significantly. In this study, we conducted industrial fermentation of RPT and observed that the levels of water extract, tea polyphenols, free amino acids, catechins, caffeine, rutin, theophylline, luteolin, and myricetin decreased, while the level of soluble sugar increased. Additionally, the levels of gallic acid, quercetin, ellagic acid, and kaempferol first increased and then decreased during fermentation. We identified a total of 731 lipids, which were classified into seven categories using a lipomics method. Among these lipids, 85 with relatively high contents decreased, while 201 lipids with low contents increased after fermentation. This led to an overall decrease in the sum contents of lipids and dominant lipids, including glycerophospholipids and saccharolipids. We also detected 33 medium- and long-chain fatty acids, with α-linolenic acid (881.202 ± 12.13–1322.263 ± 19.78 μg/g), palmitic acid (797.275 ± 19.56–955.180 ± 30.49 μg/g), and linoleic acid (539.634 ± 15.551–706.869 ± 12.14 μg/g) being the predominant ones. Coenzymes Q9 (62.76–63.57 μg/g) and Q10 (50.82–59.33 μg/g) were also identified in the fermentation process. Our findings shed light on the changes in lipids during the fermentation of RPT and highlight the potential bio-active compounds, such as α-linolenic acid, linoleic acid, Coenzymes Q9, and Q10, in ripened pu-erh tea. This contributes to a better understanding of the fermentation mechanism for RPT.

To clarify the effect and mechanism of hindered amine light stabilizer (HALS) on the UV aging behavior of asphalt binder, T622-HALS was selected as the modifier for UV aging resistance of asphalt. The physicochemical properties and microstructure of T622 light stabilizer were comprehensively analyzed. The light stabilizer-modified asphalt was prepared and placed in the UV radiation chamber for UV aging treatment. Scanning electron microscope and atomic force microscope were used to analyze the microscopic morphology evolution of light stabilizer-modified asphalt induced by UV radiation. The thermal properties and functional group composition changes in light stabilizer-modified asphalt during UV aging were studied by using the thermogravimetric and infrared spectroscopy combined testing system. The decay laws of the physical and rheological performances of light stabilizer-modified asphalt were studied during UV aging process, and the effect of light stabilizer on the UV aging behavior of asphalt binder was clarified. The research results indicated that HALSs could alleviate the microcracks and roughness change on the surface of asphalt and reduce the content of functional groups such as carbonyl and sulfoxide in asphalt. Furthermore, HALS could reduce the value difference of physical and rheological properties of asphalt before and after UV aging, significantly improving the UV aging resistance of asphalt binder.

“Ancient tea plants” are defined as tea trees > 100 years old, or with a trunk diameter > 25 cm; their leaves are manufactured to high - quality, valuable ancient plants pu-erh tea (APPT). In this study, a fermentation of APPT were developed, and outstanding sweetness of APPT infusion was observed. During fermentation, the content of soluble sugars, theabrownins (p 1.0; p 2]; While relative levels of 72 metabolites were decreased (VIP > 1.0, p

Skeletal muscle atrophy is a common muscle disease that is directly caused by an imbalance in protein synthesis and degradation. At the histological level, it is mainly characterized by a reduction in muscle mass and fiber cross-sectional area (CSA). Patients with skeletal muscle atrophy present with reduced motor ability, easy fatigue, and poor life quality. Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the degradation of heme and has attracted much attention for its anti-oxidation effects. In addition, there is growing evidence that HO-1 plays an important role in anti-inflammatory, anti-apoptosis, pro-angiogenesis, and maintaining skeletal muscle homeostasis, making it a potential therapeutic target for improving skeletal muscle atrophy. Here, we review the pathogenesis of skeletal muscle atrophy, the biology of HO-1 and its regulation, and the biological function of HO-1 in skeletal muscle homeostasis, with a specific focus on the role of HO-1 in skeletal muscle atrophy, aiming to observe the therapeutic potential of HO-1 for skeletal muscle atrophy.

AbstractObjective The present study aims to investigate the clinical and histopathological features of peritoneal endometriosis (PEM) and deep infiltrating endometriosis (DIE).Methods A total of 100 patients with PEM and DIE admitted to Dalian Women and Children’s Hospital/Dalian Women and Children’s Medical Center between October 2018 and December 2021 were selected as the study subjects. One hundred and thirty-one PEM specimens and 37 DIE were collected, 22 cases of these patients’ eutopic endometrium were used as control (15 in PEM, seven in DIE). The present study mainly analysed the pelvic distribution, the histopathological and immunohistochemical features and peritoneal invasion of PEM and DIE.Results The main distribution of PEM and DIE was located in the posterior pelvic cavity (p

Abstract Background Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. Results First, we created a mechanically injured mouse model of IUA and restored the mice’s vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1β and TNF-α in blood, and downregulated the TGF-β1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. Conclusions This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. Clinical trial registration : http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

Rice blast, caused by Magnaporthe oryzae, is a major threat to global rice production causing significant crop losses and impacting grain quality. The annual loss of rice production due to this disease ranges from 10% to 30%. The use of biologically controlled strains, instead of chemical pesticides, to control plant diseases has become a research hotspot. In this study, an antagonistic endophytic bacterial strain was isolated from the roots of Oryza officinalis using the traditional isolation and culture methods. A phylogenetic tree based on 16S RNA and whole-genome sequencing identified isolate G5 as a strain of Bacillus subtilis. This isolate displayed strong antagonistic effects against different physiological strains of M. oryzae. After co-culture in LB medium for 7 days, the inhibition rates of the mycelial growth of four strains of M. oryzae, ZB15, WH97, Guy11, and T-39800E were 98.07 ± 0.0034%, 98.59 ± 0.0051%, 99.16 ± 0.0012%, and 98.69 ± 0.0065%, respectively. Isolate G5 significantly inhibited the formation of conidia of M. oryzae, with an inhibition rate of 97% at an OD600 of 2. Isolate G5 was able to provide 66.81% protection against rice blast under potted conditions. Whole-genome sequencing revealed that the genome size of isolate G5 was 4,065,878 bp, including 4,182 coding genes. Using the anti-SMASH software, 14 secondary metabolite synthesis gene clusters were predicted to encode antifungal substances, such as fengycin, surfactin, and bacilysin. The G5 isolate also contained genes related to plant growth promotion. These findings provide a theoretical basis for expounding the biocontrol mechanisms of this strain and suggest further development of biogenic agents that could effectively inhibit rice blast pathogen growth and reduce crop damage, while being environmentally friendly, conducive to ecological development, and a sustainable alternative to chemical pesticides. This study also enriches the relevant research on endophytes of wild rice, which proves that wild rice is a valuable microbial resource bank.

BackgroundMost Chlamydia trachomatis (CT) infections are asymptomatic. The infection can persist and lead to severe sequelae. Therefore, screening for CT can primarily prevent serious sequelae.AimTo systematically evaluate CT screening from the perspective of health economics, summarize previous findings from different target populations, and make practical recommendations for developing local CT screening strategies.MethodsPubMed, Web of Science, Embase, Cochran Library, and National Health Service Economic Evaluation Database (Ovid) were searched from January 1, 2000, to March 4, 2023. Studies reporting the cost-effectiveness, cost-benefit, or cost-utility of CT screening were eligible to be included. A narrative synthesis was used to analyze and report the results following the PRISMA guidelines. The Consensus on Health Economic Criteria (CHEC) list was used to assess the methodological quality of included studies.ResultsOur review finally comprised 39 studies addressing four populations: general sexually active people (n = 25), pregnant women (n = 4), women attending STD and abortion clinics (n = 4), and other high-risk individuals (n = 6). The total number of participants was ~7,991,198. The majority of studies assessed the cost-effectiveness or cost-utility of the screening method. The results showed that the following screening strategies may be cost-effective or cost-saving under certain conditions: performing CT screening in young people aged 15–24 in the general population, military recruits, and high school students; incorporating CT screening into routine antenatal care for pregnant women aged 15–30; opportunistic CT screening for women attending STD and abortion clinics; home-obtained sampling for CT screening using urine specimens or vaginal swab; performing CT screening for 14–30-year-old people who enter correctional institutions (i.e., jail, detention) as soon as possible; providing CT screening for female sex workers (FSWs) based on local incidence and prevalence; adding routine CT screening to HIV treatment using rectal samples from men who have sex with men (MSM).ConclusionWe found that CT screening in general sexually active people aged 15–24, military recruits, high school students, pregnant women aged 15–30, women attending STD and abortion clinics, people entering jail, detention, FSWs, and MSM has health economic value. Due to the different prevalence of CT, diversities of economic conditions, and varying screening costs among different populations and different countries, regions, or settings, no uniform and standard screening strategies are currently available. Therefore, each country should consider its local condition and the results of health economic evaluations of CT screening programs in that country to develop appropriate CT screening strategies.

To clarify the effect of Hindered amine light stabilizer (HALS) on ultraviolet (UV) aging behavior of asphalt binder, the evolution history and characteristics of the UV induced micro-structure of modified asphalt were characterized. Scanning Electron Microscope (SEM) and Atomic Force Microscope (AFM) were used to analyze the microscopic morphology evolution of light stabilizer-modified asphalt during UV aging. By defining the micro-structure of asphalt in aging joints induced by UV, the identification and classification of typical micro-structure are proposed. On this basis, an evaluation method based on the morphology evolution process of modified asphalt aging was proposed to quantitatively analyze the effect of HALS on the UV aging of asphalt binder. The results show that the control effect of HALS on the UV aging behavior of asphalt can be verified by SEM and AFM detection methods. At the same time, the aging interval of the asphalt modified by hindered amine was divided by the method, and it was verified that the HALS could significantly prolong the service life of the asphalt binder. The micro-morphology of asphalt binder undergoes the process of crack generation and propagation during UV aging. The micro-morphological changes of UV aged asphalt were interfered effectively by HALS, which could alleviate and control the development of UV induced micro-cracks, and promote the fusion of micro-cracks. This study provides an effective evaluation method for detecting UV aging microscopic evolution of HALS.

In general, gearbox is prone to occur compound fault due to its harsh working environment and its fault vibration signal contains multi-components which correspond to each gearbox parts. As the multi-components are often coupled with each other and accompanied by strong noise which brings great difficulties to diagnose fault, however, the existing diagnosis methods are mainly applied on single fault rather than the entire gearbox health maintenance, therefore, this paper presents a gearbox compound fault diagnosis method and develops a diagnosis system which has potential value for gearbox health maintenance. In specific, on account of the morphological difference between multi-components, this paper uses resonance sparse signal decomposition (RSSD) to decompose the fault vibration signal into high and low resonance components respectively for achieving gearbox compound fault separation. Furthermore, as for low resonance component containing rolling bearing fault information, a weak fault feature extraction algorithm based on singular value decomposition (SVD) and cepstrum pre-whitening stochastic resonance is proposed, besides, aiming at the high resonance component containing gear fault information, an early gear fault warning algorithm based on local mean decomposition and two-dimensional approximate entropy of chaotic oscillator is also given. Finally, a gearbox fault diagnosis system, which has the ability such as the gearbox vibration signal acquisition, fault indicator warning, health status evaluation, fault signal storage is developed. Simulation validation and comparison prove the effectiveness of proposed method in this paper.

ObjectivesNeoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC.MethodsThis study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate.ResultsA total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041).ConclusionOur data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3–4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.

Background As population ageing accelerates and life expectancy increases, multimorbidity and disability pose challenges to health and social care systems worldwide. Although multimorbidity is closely related to disability, there is still a lack of research on the impact of multimorbidity on disability in rural middle-aged and elderly people. Objective To evaluate the influence of multimorbidity on disability in rural middle-aged and elderly people using the propensity-score matching (PSM) , providing a reference for formulating strategies for the management of multimorbidity and disability in this population. Methods The data of 11 088 rural middle-aged and elderly people (≥45 years old) were collected from the 2018 China Health and Retirement Longitudinal Study in March 2022, including demographics, chronic disease prevalence, and disability measured by activities of daily living (ADLs) , and instrumental activities of daily living (IADLs) . Participants were divided into multimorbidity and non-multimorbidity groups by the prevalence of multimorbidity (defined as having ≥2 chronic conditions) , and then matched using PSM with a 1∶1 ratio. Conditional Logistic regression model for paired binary data was used to assess the impact of multimorbidity on ADL disability and IADL disability. Results Of 11 088 ural middle-aged and elderly people with chronic diseases, 2 711 (24.45%) had ADL disability, 4 216 (38.02%) had IADL disability, and 7 673 (69.20%) were multimorbidity patients. The prevalence of ADL disability or IADL disability differed significantly by gender, age, marital status, education level, sleep duration, smoking, drinking, disability status, participation in social activities, and prevalence of multimorbidity (P

As a new generation of genetically engineered antibodies, recombinant antibodies are widely used in immunodetection of food hazards due to their simple structure as well as easy expression and modification. However, due to the non-directionality and imprecision of recombinant antibody preparation technology, the affinity of recombinant antibodies is low, which affects their practical application. Therefore, it is necessary to study how to improve the affinity of recombinant antibodies. This article summarizes the preparation technologies for recombinant antibodies against food hazards, describes the affinity enhancement strategies for recombinant antibodies such as mutation and evolution of recombinant antibodies, screening of mutation library, preparation of conventional multivalent antibodies, and self-assembly of antibody fusion proteins, and finally discusses the technical bottlenecks and future development directions in this field.

Abstract Background The impact of neoadjuvant chemoimmunotherapy on pulmonary resection and related outcomes had been poorly reported in previous studies. The present study aims to clarify the efficacy and safety of neoadjuvant chemoimmunotherapy, and intraoperative difficulty in the following surgery, in comparison with chemotherapy alone in non‐small cell lung cancer (NSCLC). Methods Patients with newly diagnosed clinical stages IB–IIIB(T3‐4N2) NSCLC, received neoadjuvant chemotherapy + PD‐1 inhibitors (PD‐1 + Chemo group) or chemotherapy alone (Chemo group) followed by surgery between December 2018 and December 2020 were included. The clinicopathological characteristics were retrospectively reviewed and analyzed. Results There were 69 NSCLC patients in the PD‐1 + Chemo group and 121 in the Chemo group. The major pathological response (MPR) rate in the PD‐1 + Chemo group was 49.3%, higher than that of 19.0% in the Chemo group (p 0.05). Conclusions Neoadjuvant chemoimmunotherapy for NSCLC is safe and feasible, with higher MPR rates, as well as favorable DFS than chemotherapy alone. Surgical complexity might be increased in certain patients, with comparable perioperative morbidity and mortality.

ObjectiveTo understand the testing level of the relevant laboratories and standardize the detection of porcine parvovirus (PPV) nucleic acid by implementing laboratory proficiency testing plan of the PPV nucleic acid testing.MethodsFrom January to August 2022, NIFDC organized the laboratory proficiency testing plan for PPV nucleic acid detection (plan number: NIFDC-PT-364). According to relevant CNAS standards, inactivated PPV was added into the serum of PPV negative pigs to prepare proficiency testing samples. After passing the homogeneity and stability tests, the samples should be distributed to the participating laboratories. Each laboratory was distributed 3 samples and was required to conduct qualitative detection of PPV nucleic acid, and submit the results and relevant original records within the specified time. Finally, the results submitted by each laboratory were summarized and analyzed.ResultsA total of 9 laboratories registered to participate in this proficiency testing, and all of them fed back the results within the specified time. Among them, the results of 8 laboratories met the expectations, accounting for 88.9%. Three samples from one laboratory were all tested positive for PPV, which was not consistent with the expected results, and it was judged as unsatisfactory. Most laboratories adopted real-time fluorescent PCR detection method, and used domestic reagents for nucleic acid extraction, while the PCR amplification reagents were mainly imported reagents. The use of different brands of reagents didn't have impact on the detection results. There were some problems in some laboratories, such as unclear diagram of experimental results and incomplete information of original records.ConclusionMost of the participating laboratories are capable of PPV nucleic acid detection, but the detection details need to be improved.

Diabetic macular edema(DME)is one of the vision-threatening ocular complications of diabetes and is an important cause of blindness in adults. At present, there are 141 million diabetics in China. With the increase of the number of diabetics, the incidence of DME is also increasing year by year. Modern medicine has achieved certain results in the treatment of DME, but the side effects are obvious, and the effectiveness is limited. Mingmu-11 is an effective prescription widely used in the ophthalmology of our hospital. It contains bioactive ingredients such as safranal, crocetin, curcumin, gallic acid, ellagic acid, kaempferol and vanillin. Experimental studies and clinical application reports have shown that Mingmu-11 has a protective effect on nerve damage, ischemia-reperfusion injury, inflammation, oxidative damage, microvascular damage and leakage in the pathogenesis of DME, and it can delay the progression of diabetic retinopathy(DR). The pathogenesis of DME, Mingmu-11 and its active ingredients, and the therapeutic effects on DME are reviewed.

Objective To investigate the effect of balanophora polysaccharide (BPS) on neuro-autophagy and its therapeutic effect on spinal cord injury. Methods The rats were randomly divided into sham operation group(sham, n=10),model group(SCI, n=15,which were established according to the Allen's weight-striking method), and the BPS treatment group(BPS, n=45),which were given intra-gastrically with low, medium and high dose of BPS solution for 14 days). The BBB scores were measured to evaluate motor function. Hematoxylin-Eosin and Nissl staining was used to observe the morphological changes. The expression of autophagy markers of Beclin 1, LC3-Ⅱ and p62 was detected by Western blot. Results Compared with the sham operation group,the curve of BBB score-time in SCI group was significantly lower and the injury was severer(P＜0.05). In SCI group, the dorsal white matter and central gray matter of spinal cord were seriously injured with obvious cavity. Further observation showed that the number of neurons in SCI group was significantly decreased; the structure of cell body was incomplete. The result of Western bolt showed that the relative change of LC3 Ⅱ /Ⅰ and p62 was up-regulated on day 1,7 and 14, the highest expression of both protein was found on day 7(P＜0.05). At the same time,Beclin 1 was decreased after injury with lowest expression on day 7(P＜0.05). The BBB scores of BPS group were increased with a dose-dependent manner as compared with SCI group. The cavity of dorsal white matter and central gray matter shrinked. The number of neurons was increased with intact morphology. The expression of Beclin 1 and LC3 Ⅱ/Ⅰ was increased significantly in BPS group, while p62 decreased as compared to SCI group(P＜0.05). Conclusions BPS has a well-demonstrated neuron-protective effect and the underlying mechanism might be related to the protection of injured nerve cells.

Here the authors delineate the dynamic changes in 3D genome and epigenome of differentiating macrophages and during infection with Mycobacterium tuberculosis. They reveal a role for NF-κB upon infection and identify SNPs in disease-susceptible loci, including rs1873613 that is located in the anchor of a dynamic chromatin loop.

Food provided a material foundation for the development of human society and was an important cornerstone for ensuring national security. The Chinese government has always attached great importance to food security, which is not only related to economic development and social stability but also to national security and self-reliance. As the core region for grain production and the supply of staple food in China, the major grain-producing areas account for 78.25% of the total national grain output, truly earning the title of China’s “granary”. Considering the establishment of 13 major grain-producing regions across the country in 2004 as a quasi-natural experiment, the impact of policies in major grain-producing regions on ensuring national food security is examined using a difference-in-differences method based on inter-provincial panel data for 30 provinces across the country from 1997 to 2020, and the mechanisms of their effects are further analyzed. The findings show that (1) the main producing-areas policy has a significant driving effect on China’s food security, with an average annual increase of 0.0351 units in the food-security index, and the impact is expanding year by year. (2) The policy of the main grain-producing provinces mainly plays a role in guaranteeing food security by expanding the scale of grain cultivation and the scale of family land management in the main grain-producing provinces, and the scale effect of grain cultivation has a more significant impact. Further adjusting and improving the policy of the main grain-producing areas and expanding the scale-driven effect of this policy are of great significance for transforming agricultural production methods and realizing a strong agricultural country.

The challenging international landscape and exacerbated extreme weather conditions contribute to the instability of global grain trade, complicating its impact on food security. This complexity is particularly pronounced for varieties like rice, which are heavily affected by policy-driven trade restrictions. There is insufficient research on how a country’s rice trade characteristics affect food security. A network analysis approach is adopted to intricately dissect the structural characteristics of rice trade. To explore causality with food insecurity, this paper chooses structural holes and centrality as representatives of trade network characteristics and regresses them on the food insecurity indicator. With cross-national data spanning over 30 years, the network analysis provides a clear portrayal of the dynamic changes in international rice trade. The overall resilience of the trade network has increased, but specific countries’ vulnerability has also risen. Unlike the changing trends in features observed in grain and food trade networks, there is a notable intensification in the imbalance of power distribution in the rice trade network compared to over 30 years ago. The panel data regression results show that constraint, indicating the scarcity of structural holes or connections to stronger trading partners, significantly and positively influences a country’s level of food insecurity. Based on these findings, the policy proposal for importing countries emphasizes creating strategic trade connections. By choosing appropriate trade partners that reduce constraint, food security can be enhanced, even without improvements in other conditions.

With the development of unmanned system technology,the coordination control of multiple unmanned systems has been widely concerned.Designing a reasonable coordination model is an important research content of multiple unmanned systems,but existing coordination models have security problems in the open network environment.Based on the analysis of the deficiencies of existing models,a coordination model RCC of multiple unmanned systems with security characteristics is proposed.RCC model introduces logic rules in the coordination process to provide the legality of terminals and the authority control of the communication parties,and ensures the security of multiple unmanned systems.Finally,based on ROS and RCC model,a coordination simulation platform for multiple unmanned vehicles is built,in which experiment scenes of navigation and obstacle avoi-dance are designed.Simulation results verify the practicability and security of RCC model.

ObjectiveTo examine the prevalence and influencing factors of influenza vaccination among junior high and primary school children and kindergarten children in Guiyang city of Guizhou province during an influenza season. MethodsUsing convenient sampling, we recruited 4 597 junior high/primary school and kindergarten students receiving vaccination services at 6 clinics for planned immunization in Guiyang city of Guizhou province. An online survey with a self-designed questionnaire was conducted among the students′ parents or guardians during November – December, 2020. ResultsAmong the 4 563 students with complete information, 50.14% were reported having been vaccinated against influenza, 15.76% not having been vaccinated due to lack of vaccines, 24.96% being ready to be vaccinated, and only 9.14% of the students′ parents/guardians reporting the unwillingness for their children′s influenza vaccination. The results of multivariate logistic regression analysis showed that the students′ parents/guardians with following characteristics were more likely to have their children to be vaccinated against influenza: with the children in primary school (odds ratio [OR] = 1.705, 95% confidence interval [95% CI]: 1.391 – 2.089), working as teachers (OR = 1.928, 95% CI: 1.003 – 3.706), working as medical staff (OR = 1.857, 95% CI: 1.076 – 3.204), believing in the effect of influenza vaccine against influenza infection (OR = 1.351, 95% CI: 1.145 – 1.593), having the knowledge about the requirement of annual influenza vaccination (OR = 1.749, 95% CI: 1.515 – 2.019), with the children ever having influenza vaccination before July 2020 (OR = 7.603, 95% CI: 6.512 – 8.877), and being worried about dual prevalence of coronavirus disease 2019 (COVID-19) and influenza (OR = 1.643, 95% CI: 1.390 – 1.942) (P < 0.05 for all). ConclusionUnder the circumstance of COVID-19 epidemic, the parents/guardians of junior high/primary school and kindergarten students in Guiyang city had a higher willingness for their children′s influenza vaccination in 2020 – 21 influenza season and more than a half of the students had been vaccinated by the end of December 2020. The parents′/guardians′ willingness were significantly influenced by their knowledge about influenza and influenza vaccine.

Abstract Sevoflurane has been the most widely used inhaled anesthetics with a favorable recovery profile; however, the precise mechanisms underlying its anesthetic action are still not completely understood. Here the authors show that sevoflurane activates a cluster of urocortin 1 (UCN1+)/cocaine‐ and amphetamine‐regulated transcript (CART+) neurons in the midbrain involved in its anesthesia. Furthermore, growth hormone secretagogue receptor (GHSR) is highly enriched in sevoflurane‐activated UCN1+/CART+ cells and is necessary for sleep induction. Blockade of GHSR abolishes the excitatory effect of sevoflurane on UCN1+/CART+ neurons and attenuates its anesthetic effect. Collectively, their data suggest that anesthetic action of sevoflurane necessitates the GHSR activation in midbrain UCN1+/CART+ neurons, which provides a novel target including the nucleus and receptor in the field of anesthesia.

IntroductionRecent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established.MethodsIn the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise.ResultsAfter 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) – parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression.DiscussionThese results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.

Mechanical equipment often works on variable speed condition, its corresponding vibration signal presents multi-component, modulation coupling with fast time-varying instantaneous frequency (IF), how to effectively compute IF and realize fasting varying non-stationary signal decoupling separation plays an important role in mechanical system fault diagnosis. In this paper, a sparse representation method called multi-scale chirp sparse representation (MSCSR) is introduced to identify, extract, and trend IF for achieving a highly concentrated time-frequency energy. Simulation demonstrates that the proposed method performs better than traditional IF estimation method. Furthermore, an adaptive time-varying filter is constructed using the extracted instantaneous frequency to decouple non-stationary fast signal. Ultimately, by rapid instantaneous frequency fluctuation experiment, the effectiveness of proposed method for fast strong time-varying signal is validated, it can effectively extract rapid oscillation instantaneous frequency, and the error is less than 10%.

Presently,artificial intelligence algorithms represented by deep learning have achieved advanced results and been successfully used in fields such as image classification,biometric recognition and medical assisted diagnosis by virtue of ultra-large-scale data sets and powerful computing resources.However,due to many restrictions in the actual environment,it is impossible to obtain a large number of samples or the cost of obtaining samples is too high.Therefore,studying the learning algorithm in the case of small samples is the core driving force to promote the intelligent process,and it has also become a current research hot-spot.Few-shot learning is the algorithm to learn and solve the problem under the condition of limited supervision information.Firstly,it describes the reasons why few-shot learning is difficult to generalize from the perspective of machine learning theory.Secondly,according to the design motivation of the few-shot learning algorithm,existing algorithms are classified into three categories:representation learning,data expansion and learning strategy,and their advantages and disadvantages are analyzed.Thirdly,we summarize the commonly used few-shot learning evaluation methods and the performance of existing models in public data sets.Finally,we discuss the difficulties and future research trends of small sample image classification technology to provide re-ferences for future research.

Full homomorphic encryption (FHE) supports arbitrary computation on the ciphertext without the requirement of decryption,which provides protection for privacy security in cloud computing.However,the current FHE scheme constructed using the approximate eigenvector method requires complex matrix multiplications,which is computationally complicated and cannot resist subfield attacks.In this paper,a new FHE scheme was proposed by using the power-of-prime cyclotomic ring instead of a power-of-two cyclotomic ring,and the complex matrix multiplications in homomorphic multiplications were effectively avoided by modifying the ciphertext form and decryption structure.Compared with similar schemes,the proposed scheme improves the efficiency at least by a factor of lφ(x)/2d and is secure against IND-CPA attacks.

Abstract Disturbances of circulating amino acids have been demonstrated in patients with Parkinson’s disease (PD). However, there have been no consistent results for branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), and related factors have not been explored. We aimed to explore plasma BCAA and AAA profiles in PD patients, and identify their correlations with clinical characteristics and the gut microbiota. Plasma BCAA (leucine, isoleucine, and valine) and AAA (tyrosine and phenylalanine) levels were measured in 106 PD patients and 114 controls. Fecal samples were collected from PD patients for microbiota sequencing and functional analysis. We found that plasma BCAAs and tyrosine were decreased in PD patients. BCAAs and AAAs were correlated with clinical characteristics and microbial taxa, and, in particular, they were negatively correlated with the Hoehn and Yahr stage. Compared with early PD patients, BCAA and AAA levels were even lower, and microbial composition was altered in advanced PD patients. Predictive functional analysis indicated that predicted genes numbers involved in BCAA biosynthesis were lower in advanced PD patients. What’s more, the fecal abundances of critical genes (ilvB, ilvC, ilvD, and ilvN) involved in BCAA biosynthesis were reduced and fecal BCAA concentrations were lower in advanced PD patients. In conclusion, the disturbances of plasma BCAAs and AAAs in PD patients may be related to the gut microbiota and exacerbated with PD severity. The microbial amino acid metabolism may serve as a potential mechanistic link.

The contracted family doctor services (CFDSs) is a key action selected to be implemented to deepen the reform of the pharmaceutical and healthcare system, enrich primary care services, and achieve the strategic goals of health China. Moreover, the implementation of CFDSs is a main approach to better safeguarding people's health. To effectively promote the development of CFDSs, China has successively launched various relevant supportive policies, and the local governments have been actively exploring practicing approaches. So far, remarkable results have been achieved nationwide, yet there are still many challenges, among which implementation difficulty is a major factor influencing further promotion of CFDSs. We analyzed the implementation process of CFDSs using Smith's policy implementation process model, and identified many barriers to the implementation of CFDSs, such as lack of rule of law, low level of policy executors, insufficient incentives, and impact of policy environment. In view of this, we put forward the following recommendations on exploring innovative policies for sustainable development of CFDSs: designing top-level policy objectives for CFDSs development from perspectives of law and system, improving qualities and professional identity of providers of CFDSs, establishing mutual trust between doctors and patients, and optimizing the policy implementation environment.

Abstract Background Budding yeast, Saccharomyces cerevisiae, has been extensively favored as a model organism in aging and age-related studies, thanks to versatile microfluidic chips for cell dynamics assay and replicative lifespan (RLS) determination at single-cell resolution. However, previous microfluidic structures aiming to immobilize haploid yeast may impose excessive spatial constraint and mechanical stress on cells, especially for larger diploid cells that sprout in a bipolar pattern. Results We developed a high-throughput microfluidic chip for diploid yeast long-term culturing (DYLC), optical inspection and cell-aging analysis. The DYLC chip features 1100 “leaky bowl”-shaped traps formatted in an array to dock single cells under laminar-perfused medium and effectively remove daughter cells by hydraulic shear forces. The delicate microstructures of cell traps enable hydrodynamic rotation of newborn buds, so as to ensure bud reorientation towards downstream and concerted daughter dissection thereafter. The traps provide sufficient space for cell-volume enlargement during aging, and thus properly alleviate structural compression and external stress on budding yeast. Trapping efficiency and long-term maintenance of single cells were optimized according to computational fluid dynamics simulations and experimental characterization in terms of critical parameters of the trap and array geometries. Owing to the self-filling of daughter cells dissected from traps upstream, an initial trapping efficiency of about 70% can rapidly reach a high value of over 92% after 4-hour cell culturing. During yeast proliferation and aging, cellular processes of growth, budding and daughter dissection were continuously tracked for over 60 h by time-lapse imaging. Yeast RLS and budding time interval (BTI) were directly calculated by the sequential two-digit codes indicating the budding status in images. With the employed diploid yeast strain, we obtained an RLS of 24.29 ± 3.65 generations, and verified the extension of BTI in the first couple of generations after birth and the last several generations approaching death, as well as cell de-synchronization along diploid yeast aging. Conclusions The DYLC chip offers a promising platform for reliable capture and culturing of diploid yeast cells and for life-long tracking of cell dynamics and replicative aging processes so that grasping comprehensive insights of aging mechanism in complex eukaryotic cells. Graphical Abstract

Based on the panel data of 31 provinces in China from 2005 to 2020, this paper analyzes the mechanism and spatial spillover effect of agricultural insurance on the urban–rural income gap using a fixed effect model, an intermediary effect model, and a two-stage least square method. The results show that agricultural insurance has a significant inhibitory effect on the income gap between urban and rural areas. This inhibitory effect is realized through the path of “improving the development level of agricultural insurance-improving agricultural total factor productivity-reducing the income gap between urban and rural areas”, in which the intermediary effect of agricultural total factor productivity accounts for 19.74% of the total effect. At the same time, the income gap between urban and rural areas in China exhibits typical spatial agglomeration characteristics. The western region has always been the region with the largest income gap between urban and rural areas, while the eastern region is the region with the smallest income gap between urban and rural areas. The development of agricultural insurance has had a spatial spillover effect on the income gap between urban and rural areas, and the development of agricultural insurance in neighboring areas expands the income gap between urban and rural areas in this region. In order to prevent the siphon effect, agricultural insurance investment should be increased in the neighboring regions. The results of this paper support the view of the resource flow model. Finally, we put forward some suggestions for the development of agricultural insurance, improvement in agricultural total factor productivity, and the narrowing of the income gap between urban and rural areas.

In this study, we investigated the dynamics of microbial community and flavor metabolites during the traditional fermentation of Hongqu aromatic vinegar (HAV) and subsequently explored the potential relationship between microbiota and flavor metabolites. The microbiome analysis based on high-throughput sequencing (HTS) of amplicons demonstrated that Lactobacillus, Acetobacter and Clostridium were the dominant bacterial genera, while Alternaria, Candida, Aspergillus and Issatchenkia were the dominant fungal genera during the acetic acid fermentation (AAF) of HAV. A total of 101 volatile flavor compounds were identified through gas chromatography-mass spectrometry (GC-MS) during HAV fermentation, including esters (35), alcohols (17), aldehydes (11), acids (11), ketones (7), phenols (10), and others (10). Redundancy analysis (RDA) was used to reveal the correlation between microbiota and volatile flavor compounds. Lactobacillus and Acetobacter were the two bacterial genera that have the great influence on the production of volatile flavor components in HAV. Among them, Lactobacillus was positively correlated with a variety of ethyl esters, while Acetobacter positively contributed to the formation of several organic acids. Furthermore, the non-volatile metabolites were detected by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). A total of 41 dipeptides were identified during HAV fermentation, and most of them may have sensory characteristics and biological activities. RDA showed that Aspergillus, Epicoccum, Issatchenkia, Candida and Malassezia were the most influential fungal genera on non-volatile metabolites. In particular, Epicoccum was first reported in Hongqu vinegar and showed a positive correlation with the production of various organic acids. In conclusion, this study provides a scientific basis for understanding the flavor generation mechanism of HAV, and may be valuable for developing effective techniques to select suitable strains to improve the flavor quality of HAV.