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Abstract Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.

Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection.

BackgroundFreezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson’s disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD.MethodsThis study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes.ResultsTwo patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1.ConclusionHigh-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

This paper presents an innovative thermally coupled system architecture with a parallel coolant-heated metal hydride tank (MHT) designed to satisfy the hydrogen supply requirements of proton exchange membrane fuel cell s(PEMFCs). This design solves a problem by revolutionising the cold start capability of PEMFCs at low temperatures. During the design process, LaNi5 was selected as the hydrogen storage material, with thermodynamic and kinetic properties matching the PEMFC operating conditions. Afterwards, the MHT and thermal management subsystem were customised to integrate with the 70 kW PEMFC system to ensure optimal performance. Given the limitations of conventional high-pressure gaseous hydrogen storage for cold starting, this paper provides insights into the challenges faced by the PEMFC-MH system and proposes an innovative cold start methodology that combines internal self-heating and externally assisted preheating techniques, aiming to optimise cold start time, energy consumption, and hydrogen utilisation. The results show that the PEMFC-MH system utilises the heat generated during hydrogen absorption by the MHT to preheat the PEMFC stack, and the cold start time is only 101 s, which is 59.3% shorter compared to that of the conventional method. Meanwhile, the cold start energy consumption is reduced by 62.4%, achieving a significant improvement in energy efficiency. In conclusion, this paper presents a PEMFC-MH system design that achieves significant progress in terms of time saving, energy consumption, and hydrogen utilisation.

Advances in brain imaging have led to a higher incidence of brain metastases (BM) being diagnosed. Stereotactic radiotherapy (SRS), systemic immunotherapy, and targeted drug therapy are commonly used for treating BM. In this study, we summarized the differences in overall survival (OS) between several treatments alone and in combination. We carried out a systematic literature search on Pubmed, EMBASE, and Cochrane Library. Differences in OS associated with Immune checkpoint inhibitors (ICI) alone versus targeted therapy alone and SRS + ICI or ICI alone were evaluated. This analysis was conducted on 11 studies involving 4,154 patients. The comprehensive results of fixed effect model showed that the OS of SRS + ICI group was longer than that of the ICI group (hazard ratio, 1.72; 95% CI: 1.41–2.11; P = 0.22; I 2 = 30%). The combined fixed-effect model showed that the OS time of ICI was longer than that of targeted therapy (hazard ratio, 2.09; 95% CI: 1.37–3.20; P = 0.21; I 2 = 35%). The study had a low risk of bias. In conclusion, our analysis confirmed that immunotherapy alone showed a higher OS benefit in BM patients than targeted therapy alone. The total survival time of patients with SRS combined with ICI was higher than that of patients with single ICI.

Abstract Pregnancy is a prolonged and tortuous process impairing puerperal health and life, in which uterine involution playing a decisive role. However, puerperae continually suffer from postpartum complications, whereas few research has focused on the postpartum recovery and uterine involution acceleration. The requirement for a safer and efficient therapy strategy for postpartum care is very urgent. The objective of this study was to explore the effects of Apios americana Medikus tuber to be a novel adjuvant therapy strategy for postpartum recovery. As a natural resource supplement, AM possesses multiple bioactivities and high biosafety, which also more acceptable for long treatment period during and after pregnancy. AM significantly altered the levels of estrogen, progesterone and their receptors, the secretion of transforming growth factor, matrix metalloproteinases, and inflammatory cytokines. In addition, it also significantly regulated various genes related to glucose and lipid metabolism, inflammation, and cell cycle, such as PLA2G3, EGR1, LCN2, and MMP9, thereby inhibiting inflammation and facilitating postpartum recovery and uterine involution. To conclude, our results suggested that AM as a promising supplementary food or a potential adjuvant treatment to accelerate postpartum uterine involution.

Abstract Background Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT. Methods A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented. Results Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p

Abstract Background Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with Zishen Yutai pills. However, the pharmacological mechanism of action of these pills remains unclear. Methods The compounds of Zishen Yutai pills found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of Zishen Yutai pills. The potential targets of compounds were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and Swiss Target Prediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, Therapeutic Target Database, and Genetic Association Database. The overlapping genes between the potential targets of Zishen Yutai pills’ compounds and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis. Results Nineteen compounds in Zishen Yutai pills were detected in the serum of POF mice after oral administration. A total of 695 Zishen Yutai (ZSYT) pill-related targets were screened, and 344 POF-related targets were collected. From the results of Zishen Yutai (ZSYT) pill-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with Zishen Yutai pills. Moreover, the pathway enrichment results suggested that Zishen Yutai pills treated POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis. Conclusions Via virtual screening, we found that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis was the potential therapeutic mechanism of Zishen Yutai pills in treating POF. Our study suggested that combining the analysis of Zishen Yutai pills’ compounds in blood in vivo in the POF model and network pharmacology prediction might offer a tool to characterize the mechanism of Zishen Yutai pills in the POF.

A multi-stack fuel cell system (MFCS) is a promising solution for high-power PEM fuel cell applications. This paper proposes an optimized stack allocation approach for power allocation, considering economy and dynamics to establish integrated subsystems with added functional components. The results show that an MFCS with target powers of 20 kW, 70 kW, and 120 kW satisfies lifetime and efficiency factors. The common rail buffer at the air supply subsystem inlet stabilizes pressure, buffers, and diverts. By adjusting the volume of the common rail buffer, it is possible to reduce the maximum instantaneous power and consumption of the air compressor. The integrated hydrogen supply subsystem improves hydrogen utilization and reduces parasitic power consumption. However, the integrated thermal subsystem does not have the advantages of integrated gas supply subsystems, and its thermal management performance is worse than that of a distributed thermal subsystem. This MFCS provides a solution for high-power non-average distribution PEM fuel cell systems.

Abstract Ovarian aging is characterized by a progressive decline in ovarian function. With the increase in life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Over the years, various strategies have been developed to preserve fertility in women, while there are currently no clinical treatments to delay ovarian aging. Recently, advances in biomaterials and technologies, such as three-dimensional (3D) printing and microfluidics for the encapsulation of follicles and nanoparticles as delivery systems for drugs, have shown potential to be translational strategies for ovarian aging. This review introduces the research progress on the mechanisms underlying ovarian aging, and summarizes the current state of biomaterials in the evaluation and treatment of ovarian aging, including safety, potential applications, future directions and difficulties in translation. Graphical Abstract

Following acute injury, the capillary vascular bed in the lung must be repaired to reestablish gas exchange with the external environment. Little is known about the transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation and subsequent regeneration of pulmonary capillaries, as well as their response to stress. Here, we show that the transcription factor Atf3 is essential for the regenerative response of the mouse pulmonary endothelium after influenza infection. Atf3 expression defines a subpopulation of capillary ECs enriched in genes involved in endothelial development, differentiation, and migration. During lung alveolar regeneration, this EC population expands and increases the expression of genes involved in angiogenesis, blood vessel development, and cellular response to stress. Importantly, endothelial cell-specific loss of Atf3 results in defective alveolar regeneration, in part through increased apoptosis and decreased proliferation in the endothelium. This leads to the general loss of alveolar endothelium and persistent morphological changes to the alveolar niche, including an emphysema-like phenotype with enlarged alveolar airspaces lined with regions that lack vascular investment. Taken together, these data implicate Atf3 as an essential component of the vascular response to acute lung injury that is required for successful lung alveolar regeneration.

Summary: Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration.

To describe the degradation of proton exchange membrane fuel cells (PEMFCs), empirical degradation models of different indexes of PEMFCs are established. Firstly, the simulation process and assumptions of PEMFC degradation are proposed. Secondly, the degradation simulation results including the performance and distribution indexes under the different degradation levels are conducted by AVL FIRE M. Finally, the empirical degradation models of performance and distribution indexes are established based on the above simulation results and experimental data. The results show that the relationship between the experimental and simulation results is established by the index of current density. The empirical degradation models of current density, average equilibrium potential on the cathode catalyst layer (CL), average membrane water content, average oxygen molar concentration on the cathode CL, and average hydrogen crossover flux are the linear function. The empirical degradation models of average exchange current density on the anode CL, average hydrogen molar concentration on the anode CL, and average oxygen crossover flux are the quadratic function. The empirical degradation model of average activation overpotential on the cathode CL is the quintic function.

To study the effect of component degradation on different degradation indexes of the proton exchange membrane fuel cell (PEMFC), a novel model of the PEMFC based on component properties was established. Firstly, the four main components, namely the proton exchange membrane (PEM), catalyst layer (CL), gas diffusion layer (GDL), and bipolar plate (BP), were selected. Moreover, a model of each component reflecting their properties was established and verified. Secondly, calculations of the component properties at the initial state and 5% changed were conducted. The results showed that the effects of the different components’ degradation on the different performance and distribution indexes were different. Considering the nine indexes comprehensively, the influence of component degradation on performance degradation was as follows: GDL > PEM = CL > BP.

AimsTirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy over its effectiveness, but its safety. We conducted a systematic review to assess the safety of tirzepatide.MethodsWe searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias. The systematic review was conducted via Revman5.4.ResultsNine RCTs with a total of 9818 patients were included. The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], P=0.02) and discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], P=0.007 and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], P=0.0004). It also showed that the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05); Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P

Carbon tetrachloride (CCL4) is widely used as a chemical intermediate and as a feedstock in the production of chlorofluorocarbons. CCL4 is highly toxic in the liver, kidney, testicle, brain and other tissues. However, the effect of CCL4 on ovarian function has not been reported. In this study, we found that the mice treated with CCL4 showed decreased ovarian function with disturbed estrus cycle, decreased serum level of 17β-estradiol and the reduced number of healthy follicles. Ovarian damage was accompanied by oxidative stress and the production of proinflammatory cytokines, especially interleukins. The indicators of oxidative stress, 4-Hydroxynonenal (4-HNE), 8-hydroxy-2´-deoxyguanosine (8-OHdG), 3-Nitrotyrosine (3-NT) and malondialdehyde (MDA), and the levels of proinflammatory cytokines IL-1α, IL-1β, IL-6 and IL-11 were increased, while the antioxidants, including superoxide dismutase (SOD), nuclear factor erythroid2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1), were decreased in the CCL4 group. In the CCL4 treated group, the results of Sirius Red staining, immunohistochemistry and qPCR indicated that proinflammatory cytokines caused further ovarian fibrosis. And CCL4 could also promote ovarian thecal cells to secrete inflammatory cytokines, resulting in fibrosis in vitro. In addition, CCL4 inhibited oocyte development and triggered oocyte apoptosis. In conclusion, CCL4 exposure causes ovarian damage by strong oxidative stress and the high expression of the proinflammatory cytokine mediated ovarian fibrosis.

Metal carbene is usually employed as a 1-carbon synthon or 3-carbon synthon in a variety of cycloaddition reactions. Here, the authors report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks via a β-aryl gold-carbene intermediate which reacts as a 4-carbon synthon with alkenes in [4 + 2]-cycloadditions.

Parabens, a type of endocrine-disrupting chemicals, are widely used as antibacterial preservatives in food and cosmetics in daily life. Paraben exposure has gained particular attention in the past decades, owing to its harmful effects on reproductive function. Whether low-dose paraben exposure may cause ovarian damage has been ignored recently. Here, we investigated the effects of chronic low-dose propylparaben (PrPB) exposure on ovarian function. Female C57BL/6J mice were exposed to PrPB at a humanly relevant dose for 8 months. Our results showed that chronic exposure to PrPB at a humanly relevant dose significantly altered the estrus cycle, hormone levels, and ovarian reserve, accelerating ovarian aging in adult mice. These effects are accompanied by oxidative stress enrichment, leading to steroidogenesis dysfunction and acceleration of primordial follicle recruitment. Notably, melatonin supplementation has been shown to protect against PrPB-induced steroidogenesis dysfunction in granulosa cells. Here, we report that daily chronic PrPB exposure may contribute to ovarian aging by altering oxidative stress-mediated JNK and PI3K-AKT signaling regulation, and that melatonin may serve as a pharmaceutical candidate for PrPB-associated ovarian dysfunction.

PURPOSEWe aimed to evaluate the safety and effectiveness of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) guided by multiple imaging modalities for hepatocellular carcinomas (HCCs) in special (i.e., high-risk or unfavorable) locations compared with those in conventional locations.METHODSA total of 122 HCC patients were enrolled, including 85 patients (69.7%) with HCC in conventional locations and 37 (30.3%) with HCC in special locations. The clinical data, overall survival (OS), progression-free survival (PFS), and procedure-related adverse events were analyzed.RESULTSRFA combined with TACE was successfully performed in all patients. Three complications (2.5%) occurred, with no significant difference between the conventional (n=1, 1.2%) and special (n=2, 5.4%) locations (P = 0.218). Complete tumor necrosis rate was not significantly different between the conventional (n=73, 85.9%) and special (n=34, 91.9%) locations at one-month imaging (P = 0.353). After a follow-up of 3–48 months, the PFS was 17 months for patients with HCC in conventional locations and 14 months for patients with HCC in special locations; one-year PFS rate was 68.1% in the conventional location group, not significantly (P = 0.741) different from 59.1% in the special location group. The OS was 28 months in the conventional location group while 32 months in the special location group. The cumulative one- and two-year OS rates were 89.9% and 63.3%, respectively, in the conventional location group, not significantly different from 96.3% and 65% in the special location group (P = 0.273). Age (P = 0.043) and tumor size (P < 0.001) were significant prognostic factors for OS, and tumor size (P < 0.001) was the only significant prognostic factor for PFS.CONCLUSIONRFA guided by multiple imaging modalities combined with TACE may be safe and effective for treating HCCs in special locations.

BackgroundWomen with ovarian cancer had the highest suicidal rate among all patients with gynecological malignancies, but no large studies about suicide and accidental death for women with ovarian cancers in detail were conducted. We aimed to determine the relative risk of suicide and accidental death among patients with ovarian cancer to that of the general population, and to identify risk factors associated with suicide and accidental death.MethodsData are from the SEER (surveillance, epidemiology, and end results) cancer registry of women diagnosed with ovarian cancer data from 18 registries for the years 1973–2016. The study population comprised 149,204 patients after inclusion and exclusion criteria were applied. Standardized mortality ratios (SMRs) were calculated and Fine-Gray models were fitted to identify risk factors associated with suicidal and accidental death among cancer patients, with stratifications on demographic and tumor-related characteristics.ResultsWomen with ovarian cancer had a higher risk of suicide and accidental death than the cancer-free group [SMR = 1.86; 95% CI (1.54–2.25) and SMR = 1.54; 95% CI (1.39–1.71)]. Subgroup analysis indicated that only patients with type II epithelial ovarian cancer [SMR = 2.31; 95% CI (1.83–2.91)] had an increased risk of suicide, and those with type I and type II epithelial ovarian cancer [SMR = 1.65; 95% CI (1.39–1.97) and SMR = 1.49; 95% CI (1.30–1.70)] were at a higher risk of accidental death. Patients with ovarian cancer who were younger, white, diagnosed with high-grade, non-metastatic cancer and pelvic exenteration were at a higher risk of suicide. The advanced age, earlier year of diagnosis, and non-metastatic cancer were associated with a higher risk of accidental death. Additionally, pelvic exenteration increased the risk of suicide but not the risk of accidental death among women with primary ovarian cancer.ConclusionsWomen with ovarian cancer had a higher risk of suicide and accidental death compared with the general population. The findings suggested that clinicians should identify high-risk subgroups of ovarian cancer patients for suicide and accidental death as early as possible, with appropriate prevention strategies.

Southwest China, which is rich in biodiversity and a wide range of ecosystem services (ESs), is a strong support for local human wellbeing. This area is also one of the key components of the ecological security shelter (ESS) for national ecological security and biodiversity conservation. Due to the combination of man-made and natural factors, Southwest China has suffered serious ecological degradation that directly threatens ecological security which refers to the health status of ecosystems and ESs functions. Mapping ESs-based ecological security patterns (ESPs) is essential for designing conservation strategies that suitably combine regional environment conservation with sustainable utilization. We used the InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs Tool) model to identify ecological conservation priority areas which integrated ecological sensitivity (soil erosion sensitivity, rock desertification sensitivity, landslide sensitivity, debris flow sensitivity, and freezing-thawing erosion sensitivity), ecological risk (drought risk, natural disaster risk, and socio-economic risk), and ecological conservation importance (soil conservation, water conservation, and biodiversity conservation importance). In this research, we summarized a new designing framework of ESs-based ESPs. We divided the study area into two zones and four belts including: (A) the alpine steppe and wetland zone, (B) Hengduan Mountain zone, (C) northern shelter belt (Daba-Micang Mountain), (D) central shelter belt (Wumeng-Wuling Mountain), (E) southern shelter belt (southern border of China), and (F) southwestern shelter belt (eastern Himalayas Mountain). Identifying distributions of the ESs-based ESPs has practical significance to improve local human wellbeing and to maintain sustainable development of natural-social ecosystems in Southwest China. Furthermore, ESs-based ESPs are necessary for local administrations to create rationalizing plans on balancing conservation and utilization of natural resources, so that policy-makers can put into place targeted prevention and control measures to limit the development of excessive consumption of natural resources and ecological damages, which is worth promoting.

The Hengduan Mountain is one of the biodiversity hotpots in the world and the threatened and rare flora and fauna on the mountain have been protected in nature reserves (NRs) over the past 20 years. However, limited efforts have been made in studying the benefits local people have received from the conservation, particularly from alpine nature reserves. In this study, we address this research gap by focusing on local people's perceptions of ecosystem services (ESs). We assessed local people’s perception of a broad range of ESs benefits in NRs and consequently gained insights into how they valued 20 years of conservation. Binary analysis and multiple logistic regression model were applied to identify factors that affect the local people’s perception of ES benefits. Our results indicated that most people (73%) living nearby NRs recognized ES benefits from conservation, particularly cultural services like better view (68%) and more tourists (66%). Older people, educated, and other people who utilized NRs were likely to perceive the benefits of ESs from conservation. The opinions of respondents varied with village location, the level of NRs, and the knowledge of NRs. Our results reveal that formal education, age and knowledge-related NRs played important roles in shaping local people’s perceptions of cultural ESs benefits. It suggested that adaptive management should be implemented in NRs of the Hengduan Mountain and community-based protection and harvesting measures should be implemented to enhance community-participated co-management, coupled with environmental education programs covering all people in the family. The assessment of the benefit perception of local people provides a reference for seeking higher acceptance of conservation management.

Background: Population-based data on the risk assessment of newly diagnosed cervical cancer patients' bone metastasis (CCBM) are lacking. This study aimed to develop various predictive models to assess the risk of bone metastasis via machine learning algorithms.Materials and Methods: We retrospectively reviewed the CCBM patients from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to risk factors of the presence of bone metastasis. Clinical usefulness was assessed by Akaike information criteria (AIC) and multiple machine learning algorithms based predictive models. Concordance index (C-index) and receiver operating characteristic (ROC) curve were used to define the predictive and discriminatory capacity of predictive models.Results: A total of 16 candidate variables were included to develop predictive models for bone metastasis by machine learning. The areas under the ROC curve (AUCs) of the random forest model (RF), generalized linear model (GL), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), artificial neutral network (ANN), decision tree (DT), and naive bayesian model (NBM) ranged from 0.85 to 0.93. The RF model with 10 variables was developed as the optimal predictive model. The weight of variables indicated the top seven factors were organ-site metastasis (liver, brain, and lung), TNM stage and age.Conclusions: Multiple machine learning based predictive models were developed to identify risk of bone metastasis in cervical cancer patients. By incorporating clinical characteristics and other candidate variables showed robust risk stratification for CCBM patients, and the RF predictive model performed best among these predictive models.

Our previous study demonstrated that ovarian wild-type P53-induced phosphatase 1 (WIP1) expression decreased with age. We hypothesized that WIP1 activity was related to ovarian aging. The role of WIP1 in regulating ovarian aging and its mechanisms remain to be elucidated. Adult female mice with or without WIP1 inhibitor (GSK2830371) treatment were divided into three groups (Veh, GSK-7.5, GSK-15) to evaluate the effect of WIP1 on ovarian endocrine and reproductive function and the ovarian reserve. In vitro follicle culture and primary granulosa cell culture were applied to explore the mechanisms of WIP1 in regulating follicular development. This study revealed that WIP1 expression in atretic follicle granulosa cells is significantly lower than that in healthy follicles. Inhibiting WIP1 phosphatase activity in mice induced irregular estrous cycles, caused fertility declines, and decreased the ovarian reserve through triggering excessive follicular atresia and primordial follicle activation. Primordial follicle depletion was accelerated via PI3K-AKT-rpS6 signaling pathway activation. In vitro follicle culture experiments revealed that inhibiting WIP1 activity impaired follicular development and oocyte quality. In vitro granulosa cell experiments further indicated that downregulating WIP1 expression promoted granulosa cell death via WIP1-p53-BAX signaling pathway-mediated apoptosis. These findings suggest that appropriate WIP1 expression is essential for healthy follicular development, and decreased WIP1 expression accelerates ovarian aging by promoting follicular atresia and primordial follicle activation.

Abstract Background Fluorochloridone (FLC) is a widely used herbicide, and its target organs are testes and epididymides. The Globally Harmonized System of Classification and Labelling of Chemicals classified FLC as Level 2-possibly cause fertility or fetal damage (no relevant data support). The maximum residue levels of FLC in processed crops have been reviewed in the latest European Food Safety Authority (EFSA) report in 2018. However, the toxic effect of FLC on fertility and early embryonic development is limited, and the health risk assessment of FLC needs further consideration. This study investigated the potential effects of FLC on fertility and early embryonic development in rats. Methods One hundred rats of each sex were divided into four groups including three FLC-treated groups at doses of 2 mg/kg, 5 mg/kg and 15 mg/kg, and a vehicle control group (0.5% (w/v) sodium carboxymethyl cellulose). Male and female rats were dosed for 9 and 2 consecutive weeks, intragastrically, prior to cohabitation and lasted throughout the mating period for males and continued until Gestation Day 7 (GD7) for females. Parameters such as weights and coefficients of reproductive organs, epididymal sperm number and motility, indexes of copulation, fecundity and fertility indexes, mating period, estrous cycle, corporalutea number, implantations, live, dead and resorbed fetuses, preimplantation loss rate, and postimplantation loss rate were observed in this study. Results Obvious toxicity of male reproductive system was found at the dose of 15 mg/kg including decreases in testicular and epididymal weight, also in sperm motility rate. Whereas the increase in sperm abnormality rate was observed. However, no significant effects of FLC were found on lutea count, implantations count, fetuses count and weight, live fetuses count (rate), dead fetuses count (rate), resorbed fetuses count (rate), placentas weight, fetuses gender, preimplantation loss (rate) and postimplantation loss (rate). Furthermore, FLC had no adverse effects on fertility and early embryonic development in rats. Conclusion The no-observable-adverse-effect level (NOAEL) of FLC on fertility and early embryonic development in rats was considered to be 5 mg/kg/day.

The performance of a fuel cell stack is affected by the operating temperature of the stack. The thermal management subsystem of a multi-stack fuel cell system (MFCS) is particularly significant for the operating temperature control of each stack in the MFCS. To study the influence of different topologies of a MFCS thermal management subsystem, this paper proposes and establishes two different topologies. Firstly, the integrated topology is proposed. Secondly, seven component models, namely the mixer, thermostat, radiator, tank, pump, bypass value, and proton exchange membrane fuel cell stack temperature models, are described in detail. Finally, the performance of the two topologies of the MFCS thermal management subsystem under two working conditions, steady (200 A) and variable (China heavy-duty commercial test cycle, C-WTVC), is compared. Furthermore, there are two evaluating indicators, including the stability duration and deviation of the operating temperatures of the single stack in the MFCS. Results show that when the MFCS operates under steady working conditions, the integrated topology is superior in operating temperature control accuracy (ΔT<0.5 K), while the distributed topology is superior in the adjustment process (t ≤ 100 s). Moreover, when the MFCS operates under variable working conditions, the distributed topology is superior in operating temperature control accuracy.

Objectives: Both coronavirus disease 2019 (COVID-19) pneumonia and influenza A (H1N1) pneumonia are highly contagious diseases. We aimed to characterize initial computed tomography (CT) and clinical features and to develop a model for differentiating COVID-19 pneumonia from H1N1 pneumonia.Methods: In total, we enrolled 291 patients with COVID-19 pneumonia from January 20 to February 13, 2020, and 97 patients with H1N1 pneumonia from May 24, 2009, to January 29, 2010 from two hospitals. Patients were randomly grouped into a primary cohort and a validation cohort using a seven-to-three ratio, and their clinicoradiologic data on admission were compared. The clinicoradiologic features were optimized by the least absolute shrinkage and selection operator (LASSO) logistic regression analysis to generate a model for differential diagnosis. Receiver operating characteristic (ROC) curves were plotted for assessing the performance of the model in the primary and validation cohorts.Results: The COVID-19 pneumonia mainly presented a peripheral distribution pattern (262/291, 90.0%); in contrast, H1N1 pneumonia most commonly presented a peribronchovascular distribution pattern (52/97, 53.6%). In LASSO logistic regression, peripheral distribution patterns, older age, low-grade fever, and slightly elevated aspartate aminotransferase (AST) were associated with COVID-19 pneumonia, whereas, a peribronchovascular distribution pattern, centrilobular nodule or tree-in-bud sign, consolidation, bronchial wall thickening or bronchiectasis, younger age, hyperpyrexia, and a higher level of AST were associated with H1N1 pneumonia. For the primary and validation cohorts, the LASSO model containing above eight clinicoradiologic features yielded an area under curve (AUC) of 0.963 and 0.943, with sensitivity of 89.7 and 86.2%, specificity of 89.7 and 89.7%, and accuracy of 89.7 and 87.1%, respectively.Conclusions: Combination of distribution pattern and category of pulmonary opacity on chest CT with clinical features facilitates the differentiation of COVID-19 pneumonia from H1N1 pneumonia.

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women.Methods: Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women.Results: Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, P = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (β = −0.191; 95% CI: −1.177–0.327; P = 0.001), T (β = 0.411; 95% CI: 11.154–22.709; P < 0.001), and PRL (β = 0.497; 95% CI: 10.787–20.266; P < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL.Conclusion: Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women.Clinical Trial Number: ChiCTR2000030015.

Summary: The mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury. Several reports have demonstrated that mononucleated cardiomyocytes are more responsive than are binucleated cardiomyocytes to pro-proliferative stimuli. We have developed a strategy to isolate and characterize highly enriched populations of mononucleated and binucleated cardiomyocytes at various times of development. Our results suggest that an E2f/Rb transcriptional network is central to the divergence of these two populations and that remnants of the differences acquired during the neonatal period remain in adult cardiomyocytes. Moreover, inducing binucleation by genetically blocking the ability of cardiomyocytes to complete cytokinesis leads to a reduction in E2f target gene expression, directly linking the E2f pathway with nucleation. These data identify key molecular differences between mononucleated and binucleated mammalian cardiomyocytes that can be used to leverage cardiomyocyte proliferation for promoting injury repair in the heart. : Windmueller et al. develop a strategy to separate mononucleated and binucleated cardiomyocytes and examine transcriptional differences acquired as the two subsets diverge during the neonatal period. Binucleation is associated with silencing of proliferation genes and upregulation of maturation genes. Genetic loss of Ect2 links binucleation to the Rb/E2f pathway. Keywords: cardiac regeneration, mononucleated, binucleated, cardiomyocyte, proliferation, Rb, E2f, Ect2, heart, development

Pulmonary endothelial cells (ECs) are an essential component of the gas exchange machinery of the lung alveolus. Despite this, the extent and function of lung EC heterogeneity remains incompletely understood. Using single-cell analytics, we identify multiple EC populations in the mouse lung, including macrovascular endothelium (maEC), microvascular endothelium (miECs), and a new population we have termed Car4-high ECs. Car4-high ECs express a unique gene signature, and ligand-receptor analysis indicates they are primed to receive reparative signals from alveolar type I cells. After acute lung injury, they are preferentially localized in regenerating regions of the alveolus. Influenza infection reveals the emergence of a population of highly proliferative ECs that likely arise from multiple miEC populations and contribute to alveolar revascularization after injury. These studies map EC heterogeneity in the adult lung and characterize the response of novel EC subpopulations required for tissue regeneration after acute lung injury.

Baking is widely accepted for aroma enhancement of black tea, and studies have mainly focused on the aroma or chemical substances under a specified baking condition. Understanding of the feedback between aroma substances and characteristics is urgently needed. Therefore, a mutual feedback platform (SES/MS) combined sensory evaluation system (SES) with gas chromatography–mass spectrometry (GC-MS) was established. Based on this platform, we found that baking at 90 °C for 4 h or 5 h could maintain the primary aroma attributes and increase characteristic aroma attributes—these were considered to be the best baking conditions for Yunnan congou black tea. Meanwhile, 47 volatiles were identified, among which, pyrrole and benzaldehyde appeared to have a caramel aroma, and 2-furanmethanol and α-terpineol presented a baked aroma. This study reveals the dynamic change of aroma profiles and compounds during the aroma enhancement, and provides an optional template for researchers, focused on the relationship between quality and aroma attributes of teas.

miRNAs are a category of important endogenous non-coding small RNAs and are ubiquitous in eukaryotes. They are widely involved in the regulatory process of post-transcriptional gene expression and play a critical part in the development of human diseases. By utilizing recent advancements in big data technology, using bioinformatics methods to identify causative miRNA becomes a hot spot. In this paper, a method called RNSSLFN is proposed to identify the miRNA-disease associations by reliable negative sample selection and an improved single-hidden layer feedforward neural network (SLFN). It involves, firstly, obtaining integrated similarity for miRNAs and diseases; next, selecting reliable negative samples from unknown miRNA-disease associations via distinguishing up-regulated or down-regulated miRNAs; then, introducing an improved SLFN to solve the prediction task. The experimental results on the latest data sets HMDD v3.2 and the framework of 5-fold cross-validation (CV) show that the average AUC and AUPR of RNSSLFN achieve 0.9316 and 0.9065 m, respectively, which are superior to the other three state-of-the-art methods. Furthermore, in the case studies of 10 common cancers, more than 70% of the top 30 predicted miRNA-disease association pairs are verified in the databases, which further confirms the reliability and effectiveness of the RNSSLFN model. Generally, RNSSLFN in predicting miRNA-disease associations has prodigious potential and extensive foreground.

ABSTRACT: Continental China has moved dextral Eastward since Cenozoic time, driven by the collision of the Indian with the Eurasian plate. Evidence for this comes from landscape evolution, the distribution of earthquake epicenters, Cenozoic sedimentary and volcanic rocks, and the measurement of GPS velocity vectors, the distribution of crustal stress, paleomagnetic data, and deep mantle structure, among others. This movement commenced around 40 Ma, coupled with thickened lithosphere and widespread stress release along strike-slip faults that bound the continental Chinese block. Because of continued Northward subduction of the Indian plate, manifestation of the dextral movement has intensified since 25 Ma. Far-reaching effects include extensive strike-slip movement on the Tan-Lu fault in Eastern China, formation of the Dabie ultrahigh pressure metamorphic terrane, extensive thrust faults in East China, delamination and thickening of the lithosphere of South China, a possible tectonic doubling of the Middle-Lower Yangtze Valley metallogenic belt, and the formation of the Japan, Huanghai (East China), and South China Sea.

We investigated the impact of the photoconductive properties of crystalline silicon solar cells, having a SiNx passivation film, on potential induced degradation (PID) using voltage-corona (V-Q) and self-adjusting stead state (SASS) tests. The experimental results show that the conductivity of SiNx on the cell surface was gradually enhanced by the increase in refractive index, which effectively decreased the accumulated charge on the cell surface. Thus, changes in the conductivity of SiNx were found to be the cause of the different PID performance of the modules. The present work provides a theoretical basis for solving the PID problem of solar modules and power stations, and the exploration of the V-Q and SASS techniques provides a new, convenient method and corresponding basis for testing the PID performance of solar cells during industrial production. DOI: http://dx.doi.org/10.5755/j01.ms.24.2.17171

Nano texturing has been confirmed as an effective structure to improve the efficiency of multi-crystalline silicon solar cells by reducing optical loss. In this study, nano textured solar cells are fabricated by the Reactive Ion Etching (RIE) method based on a conventional production line. Several characterization methods are employed to evaluate the morphology, minority carrier lifetime, quantum efficiency and electricity performance of both nano textured and micro textured solar cells. The results show that nano textured solar cells have a maxiumum efficiency of 19.21 % and an average efficiency that is 0.57 % higher than that of micro textured solar cells. Thus, the RIE method is an effective way to manufacture nano textured solar cells. It can demonstrably improve the photoelectric conversion efficiency of mass-produced solar cells and reduce the production cost, which is significant to the development of solar cell industy. DOI: http://dx.doi.org/10.5755/j01.ms.24.2.17398

Stable operation of fuel cell air compressions is constrained by rotating surge in low flowrate conditions. In this paper, a diagnosis criterion based on wavelet transform to solve the surge fault is proposed. First of all, the Fourier transform was used to analyze the spectral characteristics of the outlet flowrate. Before wavelet transform was used, the data are standardized. This step eliminated the influence of the flowrate’s absolute value. Then, the wavelet coefficients under characteristic frequencies were extracted. Finally, the diagnosis criterion’s threshold, which indicates the surge occurrence, was defined from the perspective of safety margin. The criterion threshold alerted a surge only 1 s after it occurred. The analysis results show that the criterion meets with the expectation, and it can be used for the control of anti-surge valve.

The purpose of this research is to develop a representative driving cycle for fuel cell logistics vehicles running on the roads of Guangdong Province for subsequent energy management research and control system optimization. Firstly, we collected and preliminarily screened the 42-day driving data of a logistics vehicle through the remote monitoring platform, and determined the vehicle characteristic signal vector for analysis. Secondly, the principal component analysis method is used to reduce the dimensionality of these characteristic parameters, avoiding the linear correlation between them and increase the comprehensiveness of the upcoming clustering. Next, the dimensionality-reduced data are fed to a clustering machine. K-means clustering method is used to gather the segmented road sections into highway, urban road, national highway and others. Finally, several segments are chosen in accordance to the occurrence possibility of the four types of road conditions, minimizing the deviation with the original data. By joining the segments and using a moving average filtering window, a typical driving cycle for this fuel cell logistics vehicle on a fixed route is constructed. Some statistical methods are done to validate the driving cycle.The effectiveness analysis shows the driving cycle we constructed has a high degree of overlap with the original data. This positive result provides a solid foundation for our follow-up research, and we can also apply this method to develop other urban driving cycles of fuel cell logistics vehicle.