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Abstract The study aimed to assess the impact of changes in blood pressure on cardiovascular events in the Chinese population. It enrolled 33 179 Chinese participants aged ≥35 years (57.1% women) without CVD at baseline. BP status was defined according to the 2017 ACC/AHA hypertension guidelines. The type of BP change was defined as change in BP status from baseline to the end of follow‐up, included stable BP

Abstract Objective To analyze the effect of transvesical laparoscopic radical prostatectomy (TVLRP) on sexual function and urinary continence. Method The data of 72 patients diagnosed with low-risk and localized prostate cancer, who underwent treatment at our hospital between January 2017 and June 2022, were retrospectively analyzed. All these patients underwent TVLRP under general anesthesia. Their serum prostate-specific antigen (PSA), urinary continence and erectile function were statistically analyzed. Results The operation went well with no intraoperative difficulties. The average surgical duration of 102 ± 22 min, coupled with the minimal intraoperative blood loss of 100 ± 32 mL, underscored the precision and efficacy of the surgical techniques employed. Following surgery, postoperative pathological assessments confirmed staging, revealing pT2a in 18 cases and pT2b in 54 cases, suggestive of localized tumors. Gleason scores ≤ 6 further indicated well-differentiated tumors, while consistently negative surgical margins affirmed the complete resection of tumors, reducing the likelihood of disease recurrence. Subsequent to the surgical intervention, the the average hospital stay was 13.94.1 days. A comprehensive 12-month follow-up revealed exceptionally high urinary continence rates, with 97.8% and 100% of patients achieving continence at 1 and 3 months postoperatively, respectively. Moreover, progressive improvement in erectile function recovery was observed, with recovery rates at 3, 6, and 12 months postoperatively reaching 82.2%, 88.4%, and 93.5%, respectively. There was no biochemical regression. Conclusion Treatment of low-risk and localized prostate cancer by TVLRP has a satisfactory urinary continence and recovery of erectile function after operation, less and complications and definite tumor-control effect.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Transgenic and pharmacological AD models are extensively studied to understand AD mechanisms and drug discovery. However, they are time-consuming and relatively costly, which hinders the discovery of potential anti-AD therapeutics. Here, we established a new model of AD in larval zebrafish by co-treatment with aluminum chloride (AlCl3) and D-galactose (D-gal) for 72 h. In particular, exposure to 150 μM AlCl3 + 40 mg/mL D-gal, 200 μM AlCl3 + 30 mg/mL D-gal, or 200 μM AlCl3 + 40 mg/mL D-gal successfully induced AD-like symptoms and aging features. Co-treatment with AlCl3 and D-gal caused significant learning and memory deficits, as well as impaired response ability and locomotor capacity in the plus-maze and light/dark test. Moreover, increased acetylcholinesterase and β-galactosidase activities, β-amyloid 1–42 deposition, reduced telomerase activity, elevated interleukin 1 beta mRNA expression, and enhanced reactive oxygen species production were also observed. In conclusion, our zebrafish model is simple, rapid, effective and affordable, incorporating key features of AD and aging, thus may become a unique and powerful tool for high-throughput screening of anti-AD compounds in vivo.

Abstract Genetic code expansion has emerged as a powerful tool for precisely introducing unnatural chemical structures into proteins to improve their catalytic functions. Given the high catalytic propensity of histidine in the enzyme pocket, increasing the chemical diversity of catalytic histidine could result in new characteristics of biocatalysts. Herein, we report the genetically encoded Nδ-Vinyl Histidine (δVin-H) and achieve the wild-type-like incorporation efficiency by the evolution of pyrrolysyl tRNA synthetase. As histidine usually acts as the nucleophile or the metal ligand in the catalytic center, we replace these two types of catalytic histidine to δVin-H to improve the performance of the histidine-involved catalytic center. Additionally, we further demonstrate the improvements of the hydrolysis activity of a previously reported organocatalytic esterase (the OE1.3 variant) in the acidic condition and myoglobin (Mb) catalyzed carbene transfer reactions under the aerobic condition. As histidine is one of the most frequently used residues in the enzyme catalytic center, the derivatization of the catalytic histidine by δVin-H holds a great potential to promote the performance of biocatalysts.

Abstract Background Glioma is considered the most common primary malignant tumor of the central nervous system. Although traditional treatments have not achieved satisfactory outcomes, recently, targeted therapies for glioma have shown promising efficacy. However, due to the single-target nature of targeted therapy, traditional targeted therapies are ineffective; thus, novel therapeutic targets are urgently needed. Methods The gene expression data for glioma patients were derived from the GEO (GSE4290, GSE50161), TCGA and CGGA databases. Next, the upregulated genes obtained from the above databases were cross-analyzed, finally, 10 overlapping genes (BIRC5, FOXM1, EZH2, CDK1, KIF11, KIF4A, NDC80, PBK, RRM2, and TOP2A) were ultimately screened and only KIF4A expression has the strongest correlation with clinical characteristics in glioma patients. Futher, the TCGA and CGGA database were utilized to explore the correlation of KIF4A expression with glioma prognosis. Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protein expression level in glioma cells, respectively. And WZ-3146, the small molecule inhibitor targeting KIF4A, were screened by Cmap analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured by the MTT, EdU, Colony formation assay and Transwell assay. Ultimately, GSEA enrichment analysis was performed to find that the apoptotic pathway could be regulated by KIF4A in glioma, in addition, the effect of WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot. Results In the present study, we confirmed that KIF4A is abnormally overexpressed in glioma. In addition, KIF4A overexpression is a key indicator of glioma prognosis; moreover, suppressing KIF4A expression can inhibit glioma progression. We also discovered that WZ-3146, a small molecule inhibitor of KIF4A, can induce apoptosis in glioma cells and exhibit antiglioma effects. Conclusion In conclusion, these observations demonstrated that targeting KIF4A can inhibit glioma progression. With further research, WZ-3146, a small molecule inhibitor of KIF4A, could be combined with other molecular targeted drugs to cooperatively inhibit glioma progression.

PurposeTreatment for advanced gallbladder cancer (GBC) remains controversial, with various recommendations regarding the choice and combination of surgery and adjuvant therapy. The present article is targeting for the exploration of optimal treatment models for advanced GBC.MethodsAJCC (American Joint Committee on Cancer, 8th edition) stage III and stage IV GBC, were defined as advanced GBC. Patients with advanced GBC were identified using the Surveillance, Epidemiology, and End Results (SEER) database and departmental cohort. Because of the most representative, only gallbladder adenocarcinoma (GBAC) patients were selected. Based on their surgical status (No, Non-radical and Radical surgery), chemotherapy status (Chemotherapy, No chemotherapy), and radiotherapy status (Radiotherapy, No radiotherapy), treatment models were categorized. For the purposes of evaluating the treatment outcomes of various treatment models and determining the risk element for cancer-specific survival (CSS), Cox regression analysis was applied. Kaplan-Meier curves were used before and after adjusting for covariates, with log-rank tests used to analyze discrepancies between curves. Immunotherapy was analyzed using clinical data from departmental cohort. Finally, to compensate for the limitations of the database, a review examines the progress in treatment models for advanced GBC.Results5,154 patients aged over 18 years with solitary primary advanced GBC were identified from the SEER database. In advanced GBC patients, the treatment model has emerged as a significant prognostic factor. “Radical surgery + Chemotherapy + Radiotherapy” models maximally improved the CSS of advanced GBC before and after adjusting for covariates, while “No surgery + No chemotherapy + No radiotherapy” model had the lowest CSS. The present conclusions were supported even after subgroup analysis by AJCC stage. The efficacy of immunotherapy was demonstrated in the departmental cohort analysis. Additionally, this article provides a comprehensive overview of recent advancements in various emerging treatment strategies.ConclusionEven when optimal treatment model cannot be pursued, providing comprehensive combinations of treatments to advanced GBC patients whenever possible is always beneficial for their survival.

BackgroundEpithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE.MethodsUsing SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented.ResultIn univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention.ConclusionFor patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.

Background Polycystic ovary syndrome (PCOS) is the most common metabolic disorder and reproductive endocrine disease, posing an elevated risk to women of reproductive age. Although metabolism differences in serum, amniotic fluid and urine have been documented in PCOS, there remains a paucity of evidence for vaginal fluid. This study aimed to identify the metabolic characteristics and potential biomarkers of PCOS in Chinese women of reproductive age. Methods We involved ten newly diagnosed PCOS women who attended gynecology at Zhongda Hospital and matched them with ten healthy controls who conducted health check-up programs at Gulou Maternal and Child Health Center in Nanjing, China from January 1st, 2019 to July 31st, 2020. Non-targeted metabolomics based on ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was applied to differentially screen vaginal metabolites between PCOS group and healthy controls. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA) and enrichment analysis were used to observe differences, search for potential biomarkers and enrich related pathways. Results Among the 20 participants, a total of 195 different metabolites were detected between PCOS group and healthy control group. PCOS and control groups were effectively separated by vaginal fluid. Lipids and lipid-like molecules constituted the majority of differential metabolites. Notably, dopamine exhibited an increased trend in PCOS group and emerged as the most significant differential metabolite, suggesting its potential as a biomarker for identifying PCOS. The application of UHPLC-MS/MS based vaginal metabolomics methods showed significant differences between PCOS and non-PCOS healthy control groups, especially linoleic acid metabolism disorder. Most differential metabolites were enriched in pathways associated with linoleic acid metabolism, phenylalanine metabolism, tyrosine metabolism, nicotinate and nicotinamide metabolism or arachidonic acid metabolism. Conclusions In this pilot investigation, significant metabolomics differences could be obtained between PCOS and healthy control groups. For PCOS women of reproductive age, vaginal metabolism is a more economical, convenient and harmless alternative to provide careful personalized health diagnosis and potential targets for therapeutic intervention.

As the communication needs in the smart distribution grid continue to rise, using existing resources to meet this growing demand poses a significant challenge. This paper researches on spectrum allocation strategies utilizing cognitive radio (CR) technology. We consider a model containing strong time-sensitive and regular communication service requirements such as distribution terminal communication services, which can be seen as a user with primary data (PD) and weak time-sensitive services such as power quality monitoring, which can be seen as a user with secondary data (SD). To fit the diversity of services in smart distribution grids (SDGs), we formulate an optimization problem with two indicators, including the sum of SD transmission rates and the maximum latency of them. Then, we analyze the two convex sub-problems and utilize convex optimization methods to obtain the optimal power and frequency bandwidth allocation for the users with SD. The simulation results indicate that, when the available transmission power of SD is low, Maximization of Transmission Sum Rate (MTSR) achieves lower maximum transmit time. Conversely, when the available transmission power is high, the performance of Minimization of the Maximum Latency (MML) is better, compared with MTSR.

ObjectivesTo investigate the prevalence of high cancer risk and its influencing factors among women aged 35 – 64 years in the agricultural and herding areas of Hinggan League, Inner Mongolia Autonomous Region, and to provide evidence for local breast cancer prevention and control in the population. MethodsFace-to-face interview with a self-designed questionnaire, clinical examination, and breast cancer screening were conducted from January to December 2022 among 5 000 women aged 35 – 64 years recruited by random sampling in the agricultural and herding areas of six prefectures/counties/banners of Hinggan League, Inner Mongolia Autonomous Region. High risk for breast cancer was assessed using the Gail model according to the determinants listed in the Guidelines and Specifications for Breast Cancer Diagnosis and Treatment of China Anti Cancer Association – 2021. Multivariate non-conditional logistic regression model was used to analyze the main factors influencing the high risk of breast cancer among the participants. ResultsOf the 49 831 valid participants, 13 334 (26.76%) were classified as being at high risk for breast cancer. The multivariate non-conditional logistic regression analysis showed that the participants with the following characteristics were more likely to be at high risk for breast cancer: age 45 – 64 years, Mongolian ethnicity, education of middle school and above, menopausal status, family history of breast cancer, history of breast surgery or biopsy, and breast skin changes on palpation; whereas belonging to other ethnic minorities, living with family members, and previous breast examination were protective factors against being at high risk for breast cancer. ConclusionThe proportion of individuals at high risk of breast cancer was relatively low among women aged 35 – 64 years in the agricultural and herding areas of Hinggan League, Inner Mongolia Autonomous Region. Age, ethnicity, education level, whether living with family members, menopausal status, family history of breast cancer, ever having had a breast examination, history of breast surgery or biopsy, and breast skin changes on palpation are the main influencing factors for having a high risk of breast cancer among women.

Deep placement of controlled-release urea is an effective fertiliser management strategy for improving the maize productivity, but it is not clear whether and how controlled-release urea depth affects the stem and root lodging of spring maize. Two consecutive years of field experiments were conducted to elucidate stem and root lodging properties and their relationship between grain yield and lodging behaviours under various controlled-release urea placement depths. Results depicted that compared to broadcast nitrogen treatment (D0), deep controlled-release urea significantly decreased the stem lodging rate by 34.7-80.4%, which contributed to improving the mechanical characteristics of the internode by optimising the internode diameter and dry matter in the third basal internode as well as higher lignin content. In addition, due to a greater and deeper root system (root dry weight, root surface area, root length and root width) as well as larger angle, diameter, and tension of aerial root that significantly decreased root lodging rate (37.0-88.4%). Furthermore, deep placement of controlled-release urea significantly increased the 100-grain weight, grain number and harvested index by constructing a deeper and larger root system, which significantly improved maize grain yield by 14.2-38.5%, and the nitrogen use efficiency increased by 4.8-10.7%. The highest grain yield, nitrogen use efficiency and lowest lodging rate occurred in controlled-release urea placement depths of 15 cm. Hence, our study suggests that controlled-release urea placement depths of 15 cm were an efficient nitrogen fertiliser management strategy to improve crop productivity as well as lodging resistance in spring maize.

Abstract Background Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. Methods We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. Results A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53–2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. Conclusion Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.

Abstract Background This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). Methods We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal–Wallis test and Mann–Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. Results We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal–Wallis test and Mann–Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. Conclusions There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Electroencephalography (EEG) analysis extracts critical information from brain signals, enabling brain disease diagnosis and providing fundamental support for brain–computer interfaces. However, performing an artificial intelligence analysis of EEG signals with high energy efficiency poses significant challenges for electronic processors on edge computing devices, especially with large neural network models. Herein, we propose an EEG opto-processor based on diffractive photonic computing units (DPUs) to process extracranial and intracranial EEG signals effectively and to detect epileptic seizures. The signals of the EEG channels within a second-time window are optically encoded as inputs to the constructed diffractive neural networks for classification, which monitors the brain state to identify symptoms of an epileptic seizure. We developed both free-space and integrated DPUs as edge computing systems and demonstrated their applications for real-time epileptic seizure detection using benchmark datasets, that is, the Children’s Hospital Boston (CHB)–Massachusetts Institute of Technology (MIT) extracranial and Epilepsy-iEEG-Multicenter intracranial EEG datasets, with excellent computing performance results. Along with the channel selection mechanism, both numerical evaluations and experimental results validated the sufficiently high classification accuracies of the proposed opto-processors for supervising clinical diagnosis. Our study opens a new research direction for utilizing photonic computing techniques to process large-scale EEG signals and promote broader applications.

Abstract Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

Abstract Background Heart failure (HF) is a heterogeneous syndrome that affects millions worldwide, resulting in substantial health and economic burdens. However, the molecular mechanism of HF pathogenesis remains unclear. Methods HF-related key genes were screened by a bioinformatics approach.The impacts of HAPLN1 knockdown on Angiotensin II (Ang II)-induced AC16 cells were assessed through a series of cell function experiments. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of oxidative stress and apoptosis-related factors. The HF rat model was induced by subcutaneous injection isoprenaline and histopathologic changes in the cardiac tissue were assessed by hematoxylin and eosin (HE) staining and echocardiographic index. Downstream pathways regulated by HAPLN1 was predicted through bioinformatics and then confirmed in vivo and in vitro by western blot. Results Six hub genes were screened, of which HAPLN1, FMOD, NPPB, NPPA, and COMP were overexpressed, whereas NPPC was downregulated in HF. Further research found that silencing HAPLN1 promoted cell viability and reduced apoptosis in Ang II-induced AC16 cells. HAPLN1 knockdown promoted left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), while decreasing left ventricular end-systolic volume (LVESV) in the HF rat model. HAPLN1 knockdown promoted the levels of GSH and suppressed the levels of MDA, LDH, TNF-α, and IL-6. Mechanistically, silencing HAPLN1 activated the PKA pathway, which were confirmed both in vivo and in vitro. Conclusion HAPLN1 knockdown inhibited the progression of HF by activating the PKA pathway, which may provide novel perspectives on the management of HF.

Abstract Background The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. Methods We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. Results Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. Conclusion Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.

Purposes The Hutuo Group belongs to the Early Proterozoic strata. As one of the most typical Paleoproterozoic strata in North China, the timing redefinition of the Hutuo Group is of great significance to the establishment of the early Precambrian stratigraphic chronology framework, the discussion of the early Precambrian geological evolution process in North China and the study of plate assembly. Methods This article conducts a detailed study of the Dongye Subgroup strata of the Hutuo Group, collecting 24 detrital zircon samples from the Jian'ancun Formation of the Hutuo Group. From 23 similar age detrital zircons, we define the weighted average age of the bottom boundary of the Hutuo Group is 2 469 Ma, and regional tectonic movements occurred in the Wutai area around 1 855 Ma. According to the 1 109 zircon ages in Hutuo Group from previous studies, we considered that the ages of >2.5 Ga are from underlying Gaofan subgroup and the maximum depositional age of Hutuo Group was early Paleoproterozoic. Findings The results show that the crust of the Wutai area was unstable at 2 376, 2 170, 2 066, 1 988, and 1 825 Ma, resulting in multiple magmatic events. The 1 825 Ma zircon age can further indicate the occurrence of the Lyuliang movement, and provide a basis for the early Proterozoic North China Craton integration.

Purpose Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria.Patients and methods Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs).Results There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p = 0.007; PFS: 15.4 months vs. 4.8 months, p

Abstract In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human‐relevant criterion for determining undernutrition weight‐for‐age z‐score (WAZ), with a cutoff point of ≤ −1.83 is established as the benchmark for identifying undernourished nonhuman primates (U‐NHPs). In U‐NHPs, pathological anomalies in multi‐organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U‐NHPs. Mitochondria dysfunction is typified by reduced mito‐number, accumulated long‐chain fatty acids, and disruption of OXPHOS complexes. Soy peptide‐treated U‐NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U‐NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re‐establish lipid metabolism balance and mitigated undernutrition.

Abstract The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation‐induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation‐induced frog skin peptide‐2 (RIFSP‐2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl‐CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP‐2 based on streptavidin‐biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP‐2 following radiation. Moreover, the decreased MUFA limited radiation‐induced and STING‐mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP‐2 and retarded tissue repair process. Altogether, RIFSP‐2 restrains radiation‐induced activation of SCD1‐MUFA‐STING axis. Thus, the stress‐induced amphibian peptides can be a bountiful source of novel radiation mitigators.

Key Clinical Message Ultrasound‐guided core needle biopsy combined with immunohistochemistry and molecular testing could improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma, help to predict distant metastasis and prognosis. Abstract Metastatic thyroid follicular carcinoma presenting initially with bone lesion is uncommon, its prime symptom is gradual onset, localized pain. Patient with bone metastasis who were diagnosed before thyroidectomy had a higher rate of mortality, clinician should be cautious in eliciting the clinical history and this insidious symptom in middle age group, carry out further examination. We are presenting two case reports of a follicular thyroid carcinoma with bone metastasis, ultrasound‐guided core needle biopsy combined with immunohistochemistry (IHC) were carried out by our clinical team to determine the source and nature of the tumor, relevant literature was reviewed, molecular testing was discussed, we believe core needle biopsy combined with IHC and molecular testing improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma.

Abstract Background In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Methods CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. Results Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Conclusion Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Spectral clustering (SC) is a hot research topic in graph theory today, which is centered on constructing similarity matrix. Many previous works have studied how to construct a higher-quality similarity matrix. However, most of these works ignore the connection between constructing similarity matrix and the overall distribution of the datasets. This problem will lead to low quality and lack of robustness in the similarity matrix when the data volume and dimensionality are expanded, which leads to poor clustering performance. Therefore, to solve the above problems, an Adaptive Fuzzy Spectral Clustering (AFSC) model is proposed in this paper. The model considers the local neighbor and global fuzzy affiliation information of the samples to construct the objective function, which can obtain the similarity matrix that satisfies the overall distribution of the datasets. Meanwhile, we propose a weight definition method to balance the above two kinds of information, which can prevent the adverse effect of information loss on the quality of the similarity matrix. The similarity matrix obtained by the AFSC model will have high quality and strong robustness, which leads to excellent clustering performance. In experiments, we verified that the AFSC model can obtain excellent clustering performance and outperform some state-of-the-art clustering models as it is applied to several datasets of different sizes and dimensions.

Abstract The search for lead compounds with anti-neuroinflammatory activity from structurally ‘optimized’ natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A–D (1–4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1–4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1–5.

Background: Osteoarthritis (OA) is the most common joint disease worldwide, but its cause remains unclear. Oestrogen protects against OA, but its clinical use is limited. G protein-coupled receptor 30 (GPR30) is a receptor that binds oestrogen, and GPR30 treatment has benefitted patients with some degenerative diseases. However, its effects on OA prevention and treatment remain unclear. Moreover, several studies have found that activation of estrogen receptors exerting anti-ferroptosis effects, which plays an important role in chondrocyte survival. Therefore, this study explored the general and ferroptosis-related effects and mechanisms of GPR30 in OA. Methods: Genome-wide RNA sequencing, western blotting, and immunohistochemistry were used to evaluate GPR30 expression and ferroptosis-related indicators in cartilage tissues from clinical patients. Next, we investigated the effects of G1 (a GPR30 receptor agonist) on the function and pathology of OA in an animal model. We also treated chondrocytes with erastin (ferroptosis agonist) plus G1, G15 (GPR30 receptor antagonist), GPR30 short hairpin RNA, or ferrostatin-1 (ferroptosis inhibitor), then measured cell viability and ferroptosis-related indices and performed proteomics analyses. Finally, western blotting and reverse transcription-polymerase chain reaction were used to assess the effects of G1 on yes-associated protein 1 (YAP1) and ferritin heavy chain 1 (FTH1) expression. Results: GPR30 expression was lower in the OA cartilage tissues than in the normal tissues, and G1 treatment significantly improved the locomotor ability of mice. Moreover, chondrocyte cell viability significantly decreased after erastin treatment, but G1 treatment concentration-dependently mitigated this effect. Furthermore, G1 treatment decreased phosphorylated YAP1 expression, increased activated YAP1 expression, and increased FTH1 transcription and protein expression, protecting against ferroptosis. Conclusion: GPR30 activation inhibited ferroptosis in chondrocytes by suppressing YAP1 phosphorylation, which regulates FTH1 expression.The Translational Potential of this Article: These results provide a novel potential target for therapeutic OA interventions.

[INLINE:1] β-Sitosterol is a type of phytosterol that occurs naturally in plants. Previous studies have shown that it has anti-oxidant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, and anti-tumor effects, but it is unknown whether β-sitosterol treatment reduces the effects of ischemic stroke. Here we found that, in a mouse model of ischemic stroke induced by middle cerebral artery occlusion, β-sitosterol reduced the volume of cerebral infarction and brain edema, reduced neuronal apoptosis in brain tissue, and alleviated neurological dysfunction; moreover, β-sitosterol increased the activity of oxygen- and glucose-deprived cerebral cortex neurons and reduced apoptosis. Further investigation showed that the neuroprotective effects of β-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke. In addition, β-sitosterol showed high affinity for NPC1L1, a key transporter of cholesterol, and antagonized its activity. In conclusion, β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Background: For static scenes with multiple depth layers, the existing defocused image deblurring methods have the problems of edge ringing artifacts or insufficient deblurring degree due to inaccurate estimation of blur amount, In addition, the prior knowledge in non blind deconvolution is not strong, which leads to image detail recovery challenge. Methods: To this end, this paper proposes a blur map estimation method for defocused images based on the gradient difference of the boundary neighborhood, which uses the gradient difference of the boundary neighborhood to accurately obtain the amount of blurring, thus preventing boundary ringing artifacts. Then, the obtained blur map is used for blur detection to determine whether the image needs to be deblurred, thereby improving the efficiency of deblurring without manual intervention and judgment. Finally, a non blind deconvolution algorithm is designed to achieve image deblurring based on the blur amount selection strategy and sparse prior. Results: Experimental results show that our method improves PSNR and SSIM by an average of 4.6% and 7.3%, respectively, compared to existing methods. Conclusions: Experimental results show that our method outperforms existing methods. Compared with existing methods, our method can better solve the problems of boundary ringing artifacts and detail information preservation in defocused image deblurring.

This study is the extension of our previous visualizing study on the commognition processes in computer-supported one-to-one tutoring. With the help of the scale of commognitive responsibility score, we found that the main triggers of the commognition process shift are the positive transfer of knowledge and cognitive conflict. On the basis of Fisher and Frey's theory and our practical experience, we suggest the online teachers to provide (1) prompts to invite; (2) robust questions to access; (3) cues to find mistakes; (4) discussion to develop and (5) spiral review to connect.