Search

Background: The burgeoning incidence and mortality rates of tumors, exacerbated by an aging population, pose a significant public health challenge in China. While global and domestic trends from 2018 to 2022 indicate a stabilization or decline in liver cancer rates, the spatiotemporal dynamics and disease burden among the elderly in Yunnan, China, remain insufficiently characterized. Methods: This study encompasses a retrospective analysis of 26,328 liver cancer patients aged 60 and above, drawn from the household population of Yunnan, China, between 2012 and 2020. The evaluation adheres to the China Cancer Registry Guidance Manual (2016) and aligns with data standards set by the International Agency for Research on Cancer (IARC) and the International Association of Cancer Registries (I-ACR). The Joinpoint software was utilized to ascertain the annual percentage change (APC) in liver cancer incidence and mortality from 2012 to 2020. Findings: Between 2012 and 2020, the incidence rate of liver cancer among the elderly in Yunnan, China, stood at 71.76 per 100,000 (CSR of 70.87 per 100,000 and WSR of 69.55 per 100,000), with a male incidence rate of 99.39 per 100,000 (CSR 99.10 per 100,000 and WSR 97.78 per 100,000) and a female rate of 45.91 per 100,000 (CSR 43.95 per 100,000 and WSR 42.54 per 100,000). The mortality rate for liver cancer in this demographic was 70.12 per 100,000 (CSR 68.43 per 100,000 and WSR 66.73 per 100,000), with males at 96.65 per 100,000 (CSR 95.61 per 100,000 and WSR 93.69 per 100,000) and females at 45.31 per 100,000 (CSR 42.63 per 100,000 and WSR 41.05 per 100,000). Liver cancer incidence among elderly males in Yunnan Province ranked third among all malignant tumors in 2012 and maintained this ranking in 2020. For elderly females, liver cancer rose from the fourth to the third position, marking an increase of one rank. Mortality rankings placed liver cancer second among males and third among females, with no change observed. Over the 2012-2020 period, the incidence rate of liver cancer in Yunnan's elderly exhibited an overall upward trajectory (APC 95% CI: 0.37%-3.8%), with male and female trends remaining stable (males: APC 95% CI: -0.35%-5.83%; females: APC 95% CI: -3.67%-7.26%). The overall mortality trend for liver cancer in the elderly was upward (APC 95% CI: 1.35% to 4.12%), with males showing an increasing trend (APC 95% CI: 0.74% to 4.51%) and females maintaining a stable rate (APC 95% CI: -0.85% to 8.0%). Interpretation: The incidence of malignant tumors correlates with the Human Development Index (HDI), with liver cancer prevalent in regions of lower HDI. While the incidence rate of liver cancer among the elderly in China has been on a downward trajectory in recent years, mirroring trends in Asia, Yunnan's elderly population defies this pattern with increasing incidence and mortality rates. This divergence from the national trend underscores the need for a focused, precision public health approach to liver cancer prevention and control, particularly among the elderly population in this underdeveloped region.

BackgroundThe mpox pandemic has caused widespread public concern around the world. The spread of misinformation through the internet and social media could lead to an infodemic that poses challenges to mpox control. ObjectiveThis review aims to summarize mpox-related infodemiology studies to determine the characteristics, influence, prevention, and control measures of the mpox infodemic and propose prospects for future research. MethodsThe scoping review was conducted based on a structured 5-step methodological framework. A comprehensive search for mpox-related infodemiology studies was performed using PubMed, Web of Science, Embase, and Scopus, with searches completed by April 30, 2024. After study selection and data extraction, the main topics of the mpox infodemic were categorized and summarized in 4 aspects, including a trend analysis of online information search volume, content topics of mpox-related online posts and comments, emotional and sentiment characteristics of online content, and prevention and control measures for the mpox infodemic. ResultsA total of 1607 articles were retrieved from the databases according to the keywords, and 61 studies were included in the final analysis. After the World Health Organization’s declaration of an mpox public health emergency of international concern in July 2022, the number of related studies began growing rapidly. Google was the most widely used search engine platform (9/61, 15%), and Twitter was the most used social media app (32/61, 52%) for researchers. Researchers from 33 countries were concerned about mpox infodemic–related topics. Among them, the top 3 countries for article publication were the United States (27 studies), India (9 studies), and the United Kingdom (7 studies). Studies of online information search trends showed that mpox-related online search volume skyrocketed at the beginning of the mpox outbreak, especially when the World Health Organization provided important declarations. There was a large amount of misinformation with negative sentiment and discriminatory and hostile content against gay, bisexual, and other men who have sex with men. Given the characteristics of the mpox infodemic, the studies provided several positive prevention and control measures, including the timely and active publishing of professional, high-quality, and easy-to-understand information online; strengthening surveillance and early warning for the infodemic based on internet data; and taking measures to protect key populations from the harm of the mpox infodemic. ConclusionsThis comprehensive summary of evidence from previous mpox infodemiology studies is valuable for understanding the characteristics of the mpox infodemic and for formulating prevention and control measures. It is essential for researchers and policy makers to establish prediction and early warning approaches and targeted intervention methods for dealing with the mpox infodemic in the future.

BackgroundYunnan province borders Myanmar, Laos, and Vietnam, giving it one of the longest borders in China. We aimed to determine the trends in prevalence and impact of COVID-19 on depressive symptoms among adolescents (12-18 years) from 2018 to 2022 in Yunnan, southwest China. ObjectiveWe evaluated the impact of the COVID-19 epidemic on adolescents’ mental health, with the aim of reducing the effect of psychological emergency syndrome and promoting healthy, happy adolescent growth. MethodsThis longitudinal, observational study used Students’ Health Survey data on adolescents’ depressive symptoms from 2018 to 2022 (before and during COVID-19) in Yunnan. We used multistage, stratified sampling in 3 prefectures in 2018 and 16 prefectures from 2019 to 2022. In each prefecture, the study population was classified by gender and residence (urban or rural), and each group was of equal size. Depressive symptoms were diagnosed based on Center for Epidemiological Studies Depression Scale (CES-D) scores. We used ANOVA to assess the differences in mean CES-D scores stratified by gender, age, residence, grade, and ethnicity. Chi-square tests were used to compare depressive symptoms by different variables. For comparability, the age-standard and gender-standard population prevalences were calculated using the 2010 China Census as the standard population. The association between COVID-19 and the risk of a standardized prevalence of depressive symptoms was identified using unconditional logistic regression analysis. ResultsThe standardized prevalence of depressive symptoms for all participants was 32.98%: 28.26% in 2018, 30.89% in 2019, 29.81% in 2020, 28.77% in 2021, 36.33% in 2022. The prevalences were 30.49% before COVID-19,29.29% in early COVID-19, and 36.33% during the COVID-19 pandemic. Compared with before COVID-19, the risks of depressive symptoms were 0.793 (95% CI 0.772-0.814) times higher in early COVID-19 and 1.071 (95% CI 1.042-1.100) times higher than during COVID-19. The average annual increase in depressive symptoms was 1.61%. During the epidemic, the prevalence of depressive symptoms in girls (36.87%) was higher than that in boys (28.64%), and the acceleration rate of girls was faster than that of boys. The prevalences of depressive symptoms and acceleration rates by age group were as follows: 27.14% and 1.09% (12-13 years), 33.99% and 1.8% (14-15 years), 36.59% and 1.65% (16-18 years). Prevalences did not differ between Han (32.89%) and minority (33.10%) populations. However, the acceleration rate was faster for the former than for the latter. The rate for senior high school students was the highest (34.94%). However, the acceleration rate for vocational high school students was the fastest (2.88%), followed by that for junior high school students (2.32%). Rural residents (35.10%) had a higher prevalence and faster acceleration than urban residents (30.16%). ConclusionsFrom 2018 to 2022, there was a significant, continuous increase in the prevalence of depressive symptoms among adolescents in Yunnan, China, especially during the COVID-19 pandemic. This represents an emergency public health problem that should be given more attention. Effective, comprehensive psychological and lifestyle intervention measures should be used to reduce the prevalence of mental health issues in adolescents.

ObjectiveTo understand the trends of nutrition in children and adolescents, which may further help to prevent and control chronic diseases in younger ages.MethodsThe Chinese National Surveys on Students' Constitution and Health (CNSSCH) in Yunnan is a survey of growth conditions, physical fitness, and health status of students in Yunnan and uses a series of complex multistage stratified sampling of seven prefectures consisting of 16 counties. Sampling schools were held constant over 35 years. The participants were randomly selected among 7–18 aged students. We used data from 1985, 1991, 2000, 2005, 2010, 2014, and 2019 CNSSCH of Yunnan. According to body mass index (BMI) criteria of National Working Group for Obesity in China (WGOC-BMI criteria), a participant's nutrition (emaciation, overweight or obesity) was defined. This study is based on survey data from 129,520 participants in 1985 (n = 14,683), 1991 (n = 4,894), 1995 (n = 6,673), 2000 (n = 9,751), 2005 (n = 23,461), 2010 (n = 22,889), 2014 (n = 23,003) and 2019 (24,166).ResultsSince 1985, the trends of emaciation over 35 years were decreasing. Regardless of gender, area, and age, the prevalence of obesity and overweight were increased. The average annual growth rate of overweight and obesity was quicker in rural areas and boys than in urban areas and girls. In Yunnan, emaciation, overweight, and obesity disparity in children were common phenomena, with differences in areas and gender.ConclusionChildren in Yunnan faced the triple burden of malnutrition (emaciation, overweight, and obesity). We should take comprehensive policies and effective intervention measures to decrease the rate of nutrition deficiencies in school-aged children.

BackgroundThe Dulong people are one of the minorities in China with the lowest population. In recent years, the lifestyle of the Dulong people has also changed drastically due to income growth and urbanization. This study aims to identify cigarette smoking prevalence and potential risk factors among Dulong adults in China.MethodsThis study was conducted among 1,018 adults based on the Dulong Health Status Investigation and Evaluation (DHSIE) in Gongshan Dulong and Nu Autonomous County of Yunnan province, Southwest China. A cross-sectional design and face-to-face questionnaire were used to collect cigarette smoking habits and demographic information. Data were weighted by post-stratification weights according to the age and gender composition of Dulong resident. We also analyzed univariate and multivariate unconditional logistic regression to explore current smoking correlates.ResultsThe weighted prevalence of ever-smoking, currently smoking, and formerly smoking among Dulong adults is 31.3, 27.7, and 3.6%, respectively. The prevalence of ever-smoking and currently smoking among male participants (57.0 and 50.6%) is much higher than that of female participants (4.0 and 3.4%). Nearly 60% of ever-smokers and current smokers smoked more than 20 cigarettes per day, which are higher than former smokers (35.2%). Among current smokers, 33.1% relapsed, and 28.3% intend to quit smoking. By adjusting for potential confounding variables, multiple logistic regression analysis indicated that male participants (OR = 48.982, 95% CI: 25.026–95.869) and current drinkers (OR = 4.450, 95% CI: 2.556–7.746) are more likely to be current smokers. On the contrary, current smokers are also more likely to be exposed to secondhand smoke (OR = 4.269, 95% CI: 2.330–7.820) and have a higher risk of chronic respiratory disease (OR = 4.955, 95% CI: 1.669–14.706).ConclusionCigarette smoking is highly prevalent among the Dulong people in Southwest China. An appropriate and effective tobacco control strategy is an urgent need for this population.

ObjectivesTo provide us with some evidence to develop more targeted stroke intervention strategies, improve the health awareness of stroke among children, and advocate the health promotion campaign of “small hands holding big hands” among parents and children, we have conducted a health education program on stroke among primary school students in Dali.MethodsThis study has applied stratified random cluster sampling in Dali of Yunnan, China. We compared the improvement of students' knowledge of stroke before and after our health education program in primary school students of Dali in October 2020. Data were collected through 3 rounds of survey by using the same questionnaire.ResultsThere were 215 participants aged 7–8 years old sampled in the first phase of the study and 145 participants in the follow-up study. The knowledge of stroke among the participants was relatively low in the pre-intervention survey. After the health education, all the indicators on stroke knowledge were improved. The correct rates in stroke definition, sequelae, and “1-2-0” identification were increased from 0 to 66.05%, to 53.95% and 64.19%, respectively, in both pre-intervention and post-intervention surveys. The correct rate of stroke knowledge was about 4.83–92.41% 3 months after the intervention. The mean score of the questionnaire was 4.25 ± 0.19 in the pre-intervention survey, and that was 15.85 ±0.27 in the post-intervention one. The mean score was 14.02 ± 0.28 post-3-month test. The score in the 3-month survey after the intervention was 11.55% lower than that in the post-intervention score.ConclusionsThe effect of stroke-related knowledge in the health education program for children is improved significantly and this can last for 3 months but it also had attenuation. We should repeat pertinent health education among students.

Abstract Background We aim to describe the prevalence and trends of hypertension among 9–17 school-aged students from 2017 to 2019 in Yunnan, China. Methods We conducted a cross-sectional study by using data from the Students’ Health Surveillance Surveys of 2017, 2018 and 2019 in Yunnan. The Students’ Health Surveillance Surveys in Yunnan collected date on physical fitness and health status of students in Yunnan through multistage-stratified sampling in 3 prefectures. In each prefecture, the study population were classified by gender and region (urban or rural), and each group had an equal size. Diagnosing criteria of hypertension was set with reference to Chinese age-specific and height-specific blood pressure (BP), to identify the abnormal status of boys and girls separately. ANOVA test was adopted to measure the differences in the mean BP stratified by gender, age, prefecture and area, and Chi-square test was used to compare the percentages of hypertension in different areas. For comparability, the age-standard and gender-standard population prevalence was calculated by directly using China Census in 2010 as a standard population. Totally 24,890 participants aged 9–17 years were included in this study. Results From 2017 to 2019, there were 24,872 students completed physical examinations and included in the analysis, of which 3288 were diagnosed with hypertension. The total prevalence of hypertension was 13.72, 12.49 and 13.45% among 9–17 years school-aged population in Yunnan, respectively. The total age-standardized hypertension prevalence trended to decrease from 13.82 to 13.48%. For urban population, the age-standardized hypertension prevalence decreased slightly from 11.24 to 10.13%. While, for rural population, it increased from 17.58 to 19.16%. The average annual growth rate in rural population was 0.53%. Conclusions From 2017to 2019, there was a significant and continuous increase in the prevalence of hypertension in 9–17 years school-aged population in Yunnan. Hypertension is epidemic among children and adolescents in Yunnan. We should take effective and comprehensive intervention measures to reduce its prevalence among school-aged children.

Objectives This study aimed to describe and quantify the relationship between body mass index (BMI) and tuberculosis (TB) incidence.Design A population-based prospective cohort study.Setting Ten randomly selected communities in the southwestern mountainous region of China.Participants Participants who had resided in study sites before screening for at least 6 months were eligible. Those who refused to participate or were temporary residents (who resided less than 6 months during three waves of screening) were excluded. The present research included 26 022 participants aged over 15 years for analyses.Interventions The cohort study conducted three rounds of TB screening from 2013 to 2015. Face-to-face surveys for participants were carried out. TB symptoms positivity suspects underwent chest X-ray and sputum smear test for diagnosis.Primary outcome measures The study outcome was the diagnosed active TB in the second and third rounds of screening.Results During the follow-up of 2.25 years, 43 cases developed TB in 44 574.4 person-years. The negative log-linear relationship between BMI and TB incidence was fitted (adjusted R2=0.76). Overweight or obese was associated with a lower risk of TB compared with normal weight (adjusted HR (aHR) 0.34, 95% CI 0.14 to 0.82). The inverse log-linear associations between continuous BMI and individual TB risk were evaluated. In subgroup analysis, the risk of TB reduced 78% in overweight or obese women (aHR 0.22, 95% CI 0.05 to 0.97), and a 64% reduction in the elderly (aHR 0.36, 95% CI 0.12 to 1.00) compared with those with normal weight, respectively.Conclusions The study provided evidence for a negative association between BMI and TB development in Chinese adults. It suggests the inverse dose–response relationship between BMI and TB incidence, and implies an optimal cut-off point of BMI for screening strategy.

BackgroundLeprosy is associated with different dermatologic and neurologic manifestations within a wide clinical spectrum, causing a great diagnostic challenge. Therefore, we aimed to examine associations between common presenting symptoms of leprosy and stage at diagnosis.Methodology/principal findingsIn this cross-sectional study, we analyzed population-level data from the Leprosy Management Information System (LEPMIS) in Yunnan, China, from 2010-2020 and enrolled patients with newly detected leprosy. The data of 2125 newly detected leprosy patients, with 5000 symptoms, were analyzed. Numbness (828/5000, 16.56%), erythema (802/5000, 16.04%), Painless nor pruritic skin lesions (651/5000, 13.02%), eyebrow hair loss (467/5000, 9.34%), and tubercles (442/5000, 8.84%) were common symptoms of leprosy. The symptoms related to skin (1935/2533, 76.39%) and leprosy reaction (279/297, 93.94%) were mainly existed in MB group. While the symptoms related to disability (263/316, 83.49%), clinical feature (38/56, 69.09%), and facial features (19/23, 82.61%) were predominantly presented in delayed diagnostic group. Despite low proportions, formic sensation (99/5000, 1.98%), pain (92/5000, 1.84%), pruritus (56/5000, 1.12%), finger contracture (109/5000, 2.18%), muscle atrophy (71/5000, 1.42%), and motor dysfunction (18/5000, 0.36%) were reported during the diagnosis of leprosy. The proportions of skin, skin and nerve, and nerve symptoms as initial symptoms were 33.25%, 44.95%, and 21.80% and as only symptoms were 28.66%, 57.81%, and 13.91%, respectively. In those with physical disability, nerve symptoms were the most frequent symptoms (57.65% and 65.36% for the initial and only symptoms, respectively) compared with skin and skin and nerve symptoms. In the delayed diagnosis group, nerve symptoms were the most frequent symptoms (15.73% and 17.25%) and were associated with the longest diagnostic intervals (mean±SD: 38.88±46.02 and 40.35±49.36 months for initial and only symptoms, respectively) when compared with skin and skin and nerve symptoms.ConclusionsUnderstanding the nature of presenting symptoms and developing symptom awareness campaigns would improve the level of leprosy awareness in the community. As nerve symptoms were related to a higher proportion of physical disability and longer diagnosis interval, we should increase awareness about nerve symptoms. Individuals with nerve symptoms should be considered the target group. Neurology outpatient visits may provide potential screening opportunities, and holding focused training for specialized neurology medical staff would enhance the capacity of the health system to recognize leprosy early.

Background Leprosy is potentially debilitating. The risk factors related to physical disabilities associated with leprosy disease in Yunnan, China was not clear. Methodology/Principal findings We studied 10644 newly detected leprosy patients from Yunnan, China, from 1990 to 2019. Factors associated with Grade 1 (G1D) and Grade 2 (G2D) physical disabilities or overall physical disabilities (combined G1D and G2D) associated with leprosy were analyzed using multinomial and ordinal logistic regression analyses. The following factors were associated with the development of physical disability in these patients with leprosy: delayed diagnosis [odds ratio (OR): 5.652, 4.399, and 2.275; 95% confidence intervals (CIs): 4.516–7.073, 3.714–5.212, and 2.063–2.509; for ≥ 10, 5–10 y, and 2–5 years, respectively], nerve damage (OR: 3.474 and 2.428; 95% CI: 2.843–4.244, and 1.959–3.008; for 2 and 1 damaged nerves, respectively), WHO classification of PB (OR: 1.759; 95% CI: 1.341–2.307), Ridley-Jopling classification (OR: 1.479, 1.438, 1.522 and 1.239; 95% CI: 1.052–2.079, 1.075–1.923, 1.261–1.838, and 1.072–1.431; for TT, BT, BB, and BL when compared with LL, respectively), advanced age (OR: 1.472 and 2.053; 95% CI: 1.106–1.960 and 1.498–2.814; for 15–59 and over 60 years old, respectively), zero skin lesions (OR: 1.916; 95% CI: 1.522–2.413), leprosy reaction (OR: 1.528; 95% CI: 1.195–1.952), rural occupation (OR: 1.364; 95% CI: 1.128–1.650), Han ethnicity (OR: 1.268; 95% CI: 1.159–1.386), and male sex (OR: 1.128; 95% CI: 1.024–1.243). Conclusions Delayed diagnosis, nerve damage, no skin lesions, WHO and Ridley-Jopling classifications, leprosy reactions, advanced age, rural occupation, Han ethnicity, and male sex were associated with disability in leprosy patients. Identifying risk factors could help to prevent physical disability. Author summary Leprosy, caused by Mycobacterium leprae (M. leprae), is a potentially disabling infectious disease. After achieving the national elimination target, the focus of leprosy care is now shifting from implementing multidrug therapy (MDT) to accelerating the reduction in disease burden, especially stopping leprosy and its complications, with targets for 2020 of 0 new child cases with Grade 2 disability (G2D) and

Leukemia inhibitory factor (LIF) is a critical cytokine involved in various biological processes, including stem cell self-renewal, inflammation, and cancer progression. Structural studies have revealed how LIF forms a functional signaling complex. However, the dynamic binding pattern of the complex remains inadequately clarified. In this study, we employed molecular dynamics (MD) simulations to investigate the recognition and binding mechanisms of LIF, revealing a preferential affinity for LIF Receptor (LIFR) over gp130, attributable to a larger buried surface area at the LIF–LIFR interface. Key residues F178 and K181 in FXXK motif, along with K124 in LIF helix B, mediate hydrophobic interactions, hydrogen bonding and allosteric regulation, collectively stabilizing the LIF-LIFR interaction. We propose that the unique N-terminal extension of LIF enables signaling without requiring the additional receptor subunit beyond gp130 and LIFR, as verified by cell proliferation assays, distinguishing it from other cytokines in the LIF family. Additionally, analysis of domain fluctuations revealed that the LIF–LIFR interface undergoes less angular displacement compared to the LIF–gp130 interface, indicating a more stable interaction with LIFR. Together, these findings provide valuable insights into the molecular basis of LIF recognition and binding, offering a dynamic foundation for cytokine engineering.

Background: The brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. Objectives: To explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. Methods: Female Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. Results: Perinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T3) levels, and both were linked to neurobehavioral disorders. Conclusion: Exposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T3 homeostasis.

Abstract Background Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis in granulosa cells (GCs), and its potential contribution to follicular dysregulation. Methods Herein, Follicular follicular fluid (FF) samples were collected from six patients with PCOS and six healthy controls undergoing in vitro fertilization-embryo transfer. The isolated extracellular vesicles were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Additionally, miRNA sequencing was performed to identify differentially expressed microRNAs, and their functions were analyzed through transcriptomics. The In vitro effects of miR-34a-5p on glycolysis, cell proliferation, and apoptosis were assessed in human ovarian granulosa tumour cell line (KGN cells). Targets of miR-34a-5p were identified by dual-luciferase reporter assays, and quantitative real-time polymerase chain reaction and western blotting were performed to determine gene and protein expression. Results The level of miR-34a-5p in FF-derived extracellular vesicles derived from patients with PCOS was significantly higher than that of the control group. Transcriptomic analysis highlighted miR-34a-5p as a key regulator of glycolysis and apoptosis. Furthermore, in vitro analysis showed that miR-34a-5p targeted lactate dehydrogenase A (LDHA), inhibited glycolysis, reduced energy supply to GCs, and promoted apoptosis of KGN cells. Conversely, miR-34a-5p inhibition restored glycolysis function and cell viability. Conclusion The findings of this study show that miR-34a-5p mediates GC apoptosis in PCOS by targeting LDHA and inhibiting glycolysis, suggesting its crucial role in PCOS pathophysiology, and offering potential therapeutic targets for improving follicular development and fertility outcomes in patients with PCOS. Further research is needed to explore the clinical implications of miR-34a-5p and its use as a biomarker for early diagnosis and prognosis of PCOS.

Introduction: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. Objectives: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. Methods: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. Results: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. Conclusion: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

Abstract This study aimed to evaluate the correlation between mental health status and arterial stiffness. A Symptom Checklist 90 (SCL-90) score was conducted for 10,688 employees of Kailuan Group Co., Ltd., of which 4936 participants received baPWV measurement. Of these, 4424 met the inclusion criteria. Based on the SCL-90 score, the study subjects were divided into normal mental health group (SCL-90 score

Abstract Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028–1.186, P

Underwater vehicles (UVs) not only play an important role in civilian fields, but have also been widely used in military fields and have broad application prospects. However, they are susceptible to the influence of the ocean current environment during underwater navigation, which makes their hydrodynamic parameters uncertain and in turn leads to difficulties in motion attitude control, navigation deviation and increased navigation cost, and even affects the completion of underwater combat tasks and the occurrence of collision accidents, thereby endangering navigation safety. Building on a summary of the current status of hydrodynamic research regarding different UVs in ocean currents and UV control methods for dealing with ocean current interference, we propose several perspectives on the development direction of UVs under ocean currents intended to provide references for the study of the influence mechanisms of complex ocean currents on the hydrodynamic parameters of UVs and the design of controllers.

Abstract Colorectal cancer (CRC) is the second common cause of cancer mortality worldwide, and it still lacks effective approaches for relapsed and metastatic CRC. Recently, oncolytic virus has been emerged as a promising immune therapeutic strategy. In this study, we develop a novel oncolytic adenovirus, rAd.mDCN.mCD40L, which drive oncolytic activity by telomerase reverse transcriptase promoter (TERTp). rAd.mDCN.mCD40L expressed both mouse genes of decorin (mDCN) and CD40 ligand (mCD40L), and produced effective cytotoxicity in both human and mouse CRC cells. Moreover, oncolytic adenovirus mediated mDCN over-expression inhibited Met expression in vitro. In CT26 subcutaneous tumor model, intratumorally delivery of oncolytic adenoviruses could inhibit tumor growth and liver metastasis, while mDCN and/or mCD40L armed oncolytic adenoviruses produced much more impressive responses. No obvious toxicity was detected in lung, liver and spleen. Moreover, mDCN and/or mCD40L armed oncolytic adenoviruses altered the immune state to activate anti-tumor responses, including increasing CD8+ T effector cells and CD4+ memory T cells, reducing MDSCs and Tregs in peripheral blood. Furthermore, mDCN and/or mCD40L armed oncolytic adenoviruses mediated mDCN and/or mCD40L expression in tumors, and up-regulated Th1 cytokines and reduced Th2 cytokines in tumors, which will be benefit for remodeling tumor microenvironment. Importantly, rAd.mDCN.mCD40L and rAd.mCD40L prevented tumor liver metastasis much more effectively than rAd.Null and rAd.mDCN. Therefore, rAd.mDCN.mCD40L and rAd.mCD40L are promising approaches for CRC therapy.

CPAMD8, a constituent of the A2M/C3 (α-2-macroglobulin/complement 3) protein family, is strikingly expressed in the human fetal lens and distal neural retina. Mutations in CPAMD8 have been linked to anterior segment dysgenesis and primary congenital glaucoma. We utilized CRISPR/Cas9 technology to establish a homozygous CPAMD8 knockout human embryonic stem cell line for differentiating retinal organoids, with the intent of exploring the role of CPAMD8 in the early development of the human eye. The CPAMD8 knockout cell line exhibits normal morphology, pluripotency, and karyotype, serving as a valuable research tool for investigating the functions of CPAMD8 in ophthalmology.

IntroductionAlthough parenting is a worthwhile and joyful process, it can also cause stress, potentially leading to parental burnout. With the implementation of the three-child policy in China, more parenting hours and higher economic costs may increase the risk of parental burnout.ObjectivesThis study investigated how was maternal parenting stress related to mothers’ parental burnout, as well as the potential mediating effect of their marital satisfaction and the moderating effect of their socioeconomic status on this relationship.MethodsData were collected from 314 mothers living in mainland China. The Chinese versions of the Parenting Burnout Assessment Scale, Parenting Stress Index, and Marriage Perception Scale were used to measure mothers’ parental burnout, parenting stress, and marital satisfaction.ResultsMothers‘ parenting stress was significantly and positively related to mothers’ parenting burnout. Mothers’ marital satisfaction mediated this relationship. Mothers’ socioeconomic status moderated the first half of the mediation model, and parenting stress exhibited a greater effect on marital satisfaction when mothers had a higher socioeconomic status.DiscussionThese findings indicated that mothers’ parenting stress could be alleviated by increasing marital satisfaction, which, in turn, reduced the risk of parental burnout. Furthermore, socioeconomic status may enhance the negative effects of parenting stress on marital satisfaction among mothers.

The human CPAMD8 gene encodes proteins in the A2M/C3 (alpha-2-macroglobulin/complement 3) family, predominantly expressed in the distal tips of the retinal neuroepithelium that form the iris and ciliary body. Mutations in CPAMD8 have been linked to anterior segment dysplasia and congenital glaucoma. Using CRISPR/Cas9 editing, we inserted a 3*EAAAK-EGFP fluorescent tag into the CPAMD8 gene, enabling real-time observation of its expression and providing insights into its biological functions. The resulting gene-edited cell line retained normal stem cell morphology and karyotype, expressed essential pluripotency markers, and exhibited differentiation potential.

mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.

Background: Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined. In this study, we aim to investigate the relationship between brain structure, functions and age, and exam the sex disparities.Method: A total of 137 healthy subjects between 20∼69 years old were enrolled with conventional MRI, structural three-dimensional T1-weighted imaging (3D-T1WI), 3D multi-echo gradient echo sequence (3D-mGRE), and 3D pseudo-continuous arterial spin labeling (3D-pCASL). Oxygen extraction fraction (OEF) and cerebral blood flow (CBF) were respectively reconstructed from 3D-mGRE and 3D-pCASL images. Cerebral metabolic rate of oxygen (CMRO2) were calculated as follows: CMRO2=CBF·OEF·[H]a, [H]a=7.377 μmol/mL. Brains were segmented into global gray matter (GM), global white matter (WM), and 148 cortical subregions. OEF, CBF, CMRO2, and volumes of GM/WM relative to intracranial volumes (rel_GM/rel_WM) were compared between males and females. Generalized additive models were used to evaluate the aging trajectories of brain structure and functions. The coupling between OEF and CBF was analyzed by correlation analysis. P or PFDR < 0.05 was considered statistically significant.Results: Females had larger rel_GM, higher CMRO2 and CBF of GM/WM than males (P < 0.05). With control of sex, CBF of GM significantly declined between 20 and 32 years, CMRO2 of GM declined subsequently from 33 to 41 years and rel_GM decreased significantly at all ages (R2 = 0.27, P < 0.001; R2 = 0.17, P < 0.001; R2 = 0.52, P < 0.001). In subregion analysis, CBF declined dispersedly while CMRO2 declined widely across most subregions of the cortex during aging. Robust negative coupling between OEF and CBF was found in most of the subregions (r range = -0.12∼-0.48, PFDR < 0.05).Conclusion: The sex disparities, age trajectories of brain structure and functions as well as the coupling of NVU in healthy individuals provide insights into normal aging which are potential targets for study of pathological conditions.

Abstract Multi-grain hole-forming sowing and uniform hole spacing are important agronomic requirements for precise hole-direct seeding of rice.This paper designs a kind of impeller type seed guiding device. The main structural parameters of the impeller seed guide device were analyzed by constructing the kinematics model of the rice seed in the impeller seed guide process. The experiment analysis were carried out with the long-grain rice variety Chuangliangyou 4418 as the seeding object. The optimal structural parameter combination of seeding-guiding device was determined as inner impeller radius 56 mm, blade offset angle 11° and seeding angle 36°. On this basis, the seeding performance test of different seed guiding devices of internal suction seed-metering device was carried out by using rice seeds with different external dimensions. The test results show that the impeller has better cavitation and hole spacing uniformity than the seed guide tube. The average hole diameter is not higher than 21.7 mm, the qualified rate of hole diameter is not lower than 96.1%, and the coefficient of variation of hole spacing is not higher than 10.1%. Compared with the seed guide tube, which is increased by 32%, 16% and 34% respectively, and the average hole distance is about 200 mm in theory.

Abstract Background Pyroptosis belongs to a unique type of programmed cell death among which GSDME is reported to exert anti-tumor immunity. However, the underlying mechanisms of how to boost tumor-infiltrating lymphocytes and whether it could benefit the efficacy of ICIs are still unknown. Methods CRC samples were used to analyze its relationship with CD8+T cells. GSDME in mouse CRC cell lines CT26/MC38 was overexpressed. The infiltration of CD8+T cells in grafted tumors was determined by multiplex flow cytometric analysis and immunohistochemistry. Transcriptomic analysis was performed in cell lines to define key signatures related to its overexpression. The mechanism of how mtDNA was released by GSDME-induced mitochondrial damage and activated cGAS-STING pathway was observed. Whether GSDME benefited ICIs and the relationships with the genotypes of CRC patients were investigated. Results It had favorable prognostic value in CRC and was positively associated with increased number and functionality of CD8+T cells both in human samples and animal models. This was due to mitochondrial damage and activation of cGAS-STING-IFNβ pathway for the recruitment of CD8+T cells. Mechanically, GSDME overexpression enhanced N-GSDME level, leading to the mitochondrial damage and mtDNA was released into cytosol. Finally, GSDME benefited with ICIs and exhibited positive relationships with MSI in CRC patients. Conclusion We presented the mechanism of GSDME in anti-tumor immunity through activating cGAS-STING-IFNβ axis mediated by mitochondrial damage, leading to more infiltration of CD8+T cells with synergistic efficacy with ICIs.

Abstract Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of LAMWA and laparoscopic hepatectomy in the treatment of small HCC.This study included 140 patients who met the inclusion criteria. Among them, 68 patients received LAMWA and 72 patients underwent laparoscopic hepatectomy. The perioperative condition, liver function recovery, the alpha fetoprotein (AFP) level, morbidities, hospitalization time, overall survival (OS), disease-free survival (DFS) and recurrence rate between the two groups were compared. The rate of complete elimination of tumor tissue was 100% and the AFP level was returned to normal within 3 months after surgery in both groups (P > 0.05). The mean alanine transaminase (ALT) and aspartate transaminase (AST) peak in the LAMWA group was lower than that in the laparoscopic hepatectomy group (259.51 ± 188.75 VS 388.9 ± 173.65, P = 0.000) and (267.34 ± 190.65 VS 393.1 ± 185.67, P = 0.000), respectively. The mean operation time in the LAMWA group was shorter than that in the laparoscopic hepatectomy group (89 ± 31 min VS 259 ± 48 min, P = 0.000). The blood loss in the LAMWA group was less than that in the laparoscopic hepatectomy group (58.4 ± 64.0 ml VS 213.0 ± 108.2 ml, P = 0.000). Compared with the laparoscopic hepatectomy group, patients in the LAMWA group had lower mean hospital stay (4.8 ± 1.2d VS 11.5 ± 2.9d, P = 0.000). The morbidities of the LAMWA group and the hepatectomy group were 14.7%(10/68) and 34.7%(25/72), respectively (P = 0.006). The one-, three-, and five-year OS rates were 88.2%, 69.9%, 45.6% for the LAMWA group and 86.1%, 72.9%, 51.4% for the laparoscopic hepatectomy group (P = 0.693). The corresponding DFS rates for the two groups were 76.3%, 48.1%, 27.9% and 73.2%, 56.7%, 32.0% (P = 0.958). Laparoscopic-assisted microwave ablation is a safe and effective therapeutic option for selected small HCC.

Abstract Recycling strategies for mixed plastics and textile blends currently aim for recycling only one of the components. Here, we demonstrate a water coupling strategy to co-hydrolyze polyester/cotton textile blends into polymer monomers and platform chemicals in gamma-valerolactone. The blends display a proclivity for achieving an augmented 5-hydroxymethylfurfural yield relative to the degradation of cotton alone. Controlled experiments and preliminary mechanistic studies underscore that the primary driver behind this heightened conversion rate lies in the internal water circulation. The swelling and dissolving effect of gamma-valerolactone on polyester enables a fast hydrolysis of polyester at much lower concentration of acid than the one in the traditional hydrolysis methods, effectively mitigating the excessive degradation of cotton-derived product and undesirable product formation. In addition, the system is also applicable to different kinds of blends and PET mixed plastics. This strategy develops an attractive path for managing end-of-life textiles in a sustainable and efficient way.

The oil content of shale oil reservoirs is a key parameter for reserve evaluation and “sweet spot” selection. However, discrepancies in the oil contents obtained by different methods have led to considerable disparities in the selection of exploration well locations and development strategies for shale oil. This study focuses on low to moderately mature sealed coring samples from the Dongying Depression in the Bohai Bay Basin. Three methods—NMR, Dean–Stark, and Rock-Eval—were employed to measure the oil content of shale. The results indicate that the oil content obtained by NMR is the highest, followed by the Dean–Stark distillation extraction method, while the pyrolysis method yields the lowest value. The study found that (1) the efficiency of the solvent extraction effect on moderately to low-mature shale is low since the occurrence of numerous closed pores leads to a lower yield when using the Dean–Stark method. (2) The exposure of shale samples to the air, sample crushing, and lag time for temperature increase cause a significant loss of light hydrocarbon components, resulting in the lowest oil content when measured by the Rock-Eval method. The NMR method, with its advantages of a short analysis time and non-destructive nature, appears to be the most advantageous method for shale oil content evaluation.

Artemisia argyi volatile oil (AAVO) is a kind of natural oil with abundant active components and remarkable medicinal and healthcare value. However, AAVO has low solubility, stability, and bioavailability. Here, to address these issues, a nanoemulsion system of Artemisia argyi volatile oil (AAVO-Ne) is constructed using phase transition titration, and the conditions are continuously optimized to combine it with chitosan, forming a chitosan composite of the volatile oil nanoemulsion (AAVO-NeCs). The structure was analyzed using Fourier transform infrared (FT-IR) spectroscopy, and the performance was evaluated through in vitro antibacterial tests, in vitro release experiments, and antioxidant assays. The results indicated that the typical characteristic absorption peaks of AAVO shifted in the AAVO-Ne spectrum and new absorption peaks appeared in the AAVO-NeCs, which implied that the formation of AAVO-NeCs involved not only a physical encapsulation process but also certain chemical interactions, thus enhancing the stability and bioactivity of the composites. Compared to AAVO, AAVO-NeCs exhibited a 1.87-fold increase in antibacterial activity against antibiotic-resistant bacteria. Meanwhile, the in vitro release study demonstrated that AAVO-NeCs exhibited a biphasic release pattern. Compared to AAVO-Ne and AAVO, AAVO-NeCs also showed a significant enhancement in antioxidant activity. Overall, AAVO-NeCs demonstrate improved solubility and efficacy of AAVO, as well as high-efficiency delivery, antibacterial, sustained-release, and antioxidant properties. These attributes position AAVO-NeCs as a promising candidate for applications in drug delivery, food preservation, and other fields, offering innovative solutions and contributing to the sustainable development of related industries.

Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification. Methods: We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice. Results: Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response. Conclusions: Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV.

In actual industrial scenarios, collecting a complete dataset with all fault categories under the same conditions is challenging, leading to a loss in fault category knowledge in single-source domains. Deep learning domain adaptation methods face difficulties in multi-source scenarios due to insufficient labeled data and significant distribution differences, hindering domain-specific knowledge transfer and reducing fault diagnosis efficiency. To address these issues, the Dynamic Similarity-guided Multi-source Domain Adaptation Network (DS-MDAN) is proposed. This method leverages incomplete data from multiple-source domains to address distribution disparities in deep domain adaptation. It enhances diagnostic performance in the target domain by transferring knowledge across diverse domains. DS-MDAN uses convolution kernels of different scales to extract multi-scale feature information and achieves feature fusion through upsampling and operations like addition and concatenation. Adversarial training with domain and fault classifiers optimizes feature extraction for widely applicable representations. The similarity between source and target domain data is calculated based on features extracted by a shared-weight network, dynamically adjusting the contribution of different source domain data to minimize distribution differences. Finally, matched source and target domain samples are mapped to the same feature space for fault diagnosis. Experimental validation on various bearing fault datasets shows that DS-MDAN improves performance in multiple fault diagnosis tasks, increasing accuracy and demonstrating good generalization capabilities.

Wound healing is a complicated obstacle, especially for chronic wounds. Mesenchymal stem cell-derived exosomes may be a promising cell-free approach for treating skin wound healing. Exosomes can accelerate wound healing by attenuating inflammation, promoting angiogenesis, cell proliferation, extracellular matrix production and remodeling. However, many issues, such as off-target effects and high degradation of exosomes in wound sites need to be addressed before applying into clinical therapy. Therefore, the bioengineering technology has been introduced to modify exosomes with greater stability and specific therapeutic property. To prolong the function time and the local concentration of exosomes in the wound bed, the use of biomaterials to load exosomes emerges as a promising strategy. In this review, we summarize the biogenesis and characteristics of exosomes, the role of exosomes in wound healing, and the therapeutic applications of modified-exosomes in wound healing. The challenges and prospects of exosomes in wound healing are also discussed.

Abstract Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products.

Abstract Endothelial programmed death‐ligand 1 (PD‐L1) expression is higher in tumors than in normal tissues. Also, tumoral vasculatures tend to be leakier than normal vessels leading to a higher trans‐endothelial or transmural fluid flow. However, it is not clear whether such elevated transmural flow can control endothelial PD‐L1 expression. Here, a new microfluidic device is developed to investigate the relationship between transmural flow and PD‐L1 expression in microvascular networks (MVNs). After treating the MVNs with transmural flow for 24 h, the expression of PD‐L1 in endothelial cells is upregulated. Additionally, CD8 T cell activation by phytohemagglutinin (PHA) is suppressed when cultured in the MVNs pre‐conditioned with transmural flow. Moreover, transmural flow is able to further increase PD‐L1 expression in the vessels formed in the tumor microenvironment. Finally, by utilizing blocking antibodies and knock‐out assays, it is found that transmural flow‐driven PD‐L1 upregulation is controlled by integrin αVβ3. Overall, this study provides a new biophysical explanation for high PD‐L1 expression in tumoral vasculatures.

Mutation of the MAPK7 gene was related to human scoliosis. Mapk7 regulated the development of limb bones and skulls in mice. However, the role of MAPK7 in vertebral development is still unclear. In this study, we constructed Col2a1-cre; Mapk7f/f transgenic mouse model to delete Mapk7 in cartilage, which displayed kyphosis and osteopenia. Mechanistically, Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes, which impaired chondrocyte hypertrophy and attenuated vertebral ossification. In vivo, systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 deficiency. Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development, which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

Abstract Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein representation, dual-path protein encoding using pre-training, and function annotation by long short-term memory-based decoding. A variety of case studies based on different benchmarks were conducted, which confirmed the superior performance of AnnoPRO among available methods. Source code and models have been made freely available at: https://github.com/idrblab/AnnoPRO and https://zenodo.org/records/10012272

Abstract Background The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. Methods We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P

The rapid development of Low Earth Orbit (LEO) satellite navigation systems requires modulation schemes with strong anti-jamming capabilities, high spectral efficiency, and the ability to achieve precise tracking in high-dynamic environments. Traditional Binary Offset Carrier (BOC) modulation suffers from multi-peak ambiguity, leading to false lock issues. To address this, FH-BOC modulation, which integrates BOC modulationand frequency hopping, significantly improves both anti-jamming performance and spectral efficiency. Against this background, this paper proposes a comprehensive high-dynamic tracking algorithm for FH-BOC signals. (1) Based on the adaptive Kalman filter algorithm, high-precision carrier tracking was achieved in high-dynamic environments. (2) By leveraging the correlation between the ranging code and frequency-hopping offset carrier, a composite pseudo-code is generated through the XOR operation, and a corresponding composite code-tracking loop is introduced. (3) Based on code loop tracking results, the frequency-hopping moments of the subcarrier are detected, and a phase-locked loop for the frequency-hopping subcarrier is established. Simulation results indicate that the algorithm achieves centimeter-level pseudorange measurement accuracy for FH-BOC navigation signals under the JPL high-dynamic model.

Background: The clinical evaluation for disuse muscle atrophy usually depends on qualitative rating indicators with subjective judgments of doctors and some invasive measurement methods such as needle electromyography. Surface electromyography, as a non-invasive method, has been widely used in the detection of muscular and neurological diseases in recent years. In this paper, we explore how to evaluate disuse muscle atrophy based on surface electromyography; Methods: Firstly, we conducted rat experiments using hind-limb suspension to create a model of disuse muscle atrophy. Five groups of rats were suspended for 0, 3, 7, 14, and 21 days, respectively. We induced leg electromyography of rats through electrical stimulation and used fluorescence staining to obtain the fiber-type composition of rats’ leg muscles. We obtained the best-fitting frequency bands of power spectrum density of surface electromyography for type I and type II fibers in rats’ leg muscles by changing the frequency band boundaries. Secondly, we conducted tests on the human body and collected the electromyography of the atrophied muscles of the subjects over a period of 21 days. The changes in muscle fiber composition were evaluated using the frequency bands of power spectrum density obtained from rat experiments. The method was to evaluate the changes in type I fibers by the changes in the area of the best-fitting frequency band of type I fibers and to evaluate the changes in type II fibers by the changes in the area of the best-fitting frequency band of type II fibers. Results: The results of rat experiments showed that type I fibers best fit the frequency band of 20–330 Hz and type II fibers best fit the frequency band of 176–500 Hz. The results of human testing showed that the atrophy of the two types of fibers was consistent with the changes in the areas of the corresponding best-fitting frequency bands. Conclusions: The test results demonstrate the feasibility of using surface electromyography to evaluate muscle fiber-type composition and subsequently assess muscle atrophy. Further research may contribute to the diagnosis and treatment of disuse muscle atrophy.

As unmanned aerial vehicles (UAVs) are widely used in various fields, there is an increasing demand for UAV anti-jamming, multipath mitigation, and covert secrecy. Frequency-hopping binary offset carrier (FH-BOC) signals possess higher anti-jamming and multipath mitigation capabilities than direct-sequence spread spectrum (DSSS) and binary offset carrier (BOC) signals. A prerequisite for constructing communication links between UAVs using FH-BOC signals is the design of efficient acquisition algorithms to capture the signals successfully. In this paper, the modulation and characteristics of the FH-BOC signal are introduced. The maximum relative velocity between UAVs is 5.5 km/s, the maximum acceleration is 50 g, and the maximum plus acceleration is 20 g/s. In this high dynamic environment, the parameters for the parallel code phase and Partial Matched Filter–Fast Fourier Transform (PMF-FFT) acquisition algorithms targeting FH-BOC(10,1) signals are designed, and the acquisition performance of these algorithms is comparatively analyzed. The acquisition time for the first and second algorithms is 4.3317 s and 6.137 s. The number of real additions required by the first and second algorithms is approximately 10.9×109 and 8.9×109, and the number of real multiplications is approximately 7.6×109 and 6.7×109. This helps in selecting the acquisition algorithm when FH-BOC signals are used to build inter-UAV communication links.

Adding an insulating sheath to the exposed metal part of the outer insulation of a roof cable terminal can extend the creepage distance of the leakage current and significantly reduce the probability of pollution flashover on the outer insulation of the equipment. However, during the actual operation of the locomotive, the inner surface of the insulating sheath is discharged, resulting in cable insulation breakdown, the mechanism of which is unclear. This paper establishes a cable terminal–sheath electric field simulation model and studies the interface air gap, the interface with wet pollution, and the distribution of damp pollution on the outer surface and other factors on the electric field distribution of the cable terminal–sheath structure and the interface discharge, revealing the mechanism of discharge on the inner surface of the cable terminal’s insulation sheath. A voltage of 25 kV rms is applied, and the simulation results show that when the outer surface of the cable terminal is clean and there are air gaps and wet dirt on the inner surface, the maximum distortion electric field at the inner surface is 0.8 × 105~3.4 × 105 V/m, and the value of the electric field at this time is not enough to cause a partial discharge; when there is a uniform layer of wet dirt on the outer surface of the cable terminal, the electric field on the inner surface averages 1.5 × 105 V/m, which is about 275% higher than the average electric field when the outer surface is clean; when there is wetting or an air gap on the inner surface at the same time, the maximum aberration electric field on the inner surface is 1.8 × 105~1.9 × 106 V/m. The wetting on the outer surface of the cable terminal strengthens the non-uniformity degree of the distribution of the electric field, and when there is wetting and an air gap on the inner surface, the over-voltage on the cable terminal inevitably leads to a discharge phenomenon in the air gap. This provides a theoretical basis for optimizing the insulation sheath structure to solve the discharge problem.