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Ecological restoration projects implemented over the past 20 years have substantially increased forest coverage in China, but the high tree mortality of new afforestation forest remains a challenging but unsolved problem. It is still not clear how much vegetation can be sustained by the forest lands with given water, energy and soil conditions, i.e., the carrying capacity for vegetation (CCV) of forest lands, which is the prerequisite for planning and implementing forest restoration projects. Here, we used a simplified method to evaluate the CCV across forest lands nationwide. Specifically, based on leaf area index (LAI) dataset, we use boosted regression tree and multiple linear regression model to analyze the CCV during 2001–2020 and 2021–2030 and explore the contribution of environmental factors. We find that there are three typical regions with lower CCV located in the Loess Plateau and the southern region of the Inner Mongolia Plateau, the Hengduan Mountain region, and the Tianshan Mountains. More importantly, the vegetation in the regions near the dry-wet climate transition zone show excess local carrying capacity for vegetation over the past two decades and they are more susceptible to potential climatic stress. In comparison, in the Greater Khingan Mountains and Hengduan Mountains, there is high potential to improve the forest growth. Temperature, precipitation and soil affects the CCV by shaping the vegetation in the optimal range. This indicates that more consideration should be given to restrictions of regional environmental constraints when planning afforestation and forest management. This study has important implications for guiding future forest scheme in China.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P

Abstract Objective Osteoporosis is a global health issue characterized by decreased bone mass and microstructural degradation, leading to an increased risk of fractures. This study aims to explore the molecular mechanism by which P2X7 receptors influence osteoclast formation and bone resorption through the PI3K-Akt-GSK3β signaling pathway. Methods An osteoporosis mouse model was generated through ovariectomy (OVX) in normal C57BL/6 and P2X7f/f; LysM-cre mice. Osteoclasts were isolated for transcriptomic analysis, and differentially expressed genes were selected for functional enrichment analysis. Metabolite analysis was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS), and multivariate statistical analysis and pattern recognition were used to identify differential lipid metabolism markers and their distribution. Bioinformatics analyses were conducted using the Encyclopedia of Genes and Genomes database and the MetaboAnalyst database to assess potential biomarkers and create a metabolic pathway map. Osteoclast precursor cells were used for in vitro cell experiments, evaluating cell viability and proliferation using the Cell Counting Kit 8 (CCK-8) assay. Osteoclast precursor cells were induced to differentiate into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-beta ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) staining was performed to compare differentiation morphology, size, and quantity between different groups. Western blot analysis was used to assess the expression of differentiation markers, fusion gene markers, and bone resorption ability markers in osteoclasts. Immunofluorescence staining was employed to examine the spatial distribution and quantity of osteoclast cell skeletons, P2X7 protein, and cell nuclei, while pit assay was used to evaluate osteoclast bone resorption ability. Finally, in vivo animal experiments, including micro computed tomography (micro-CT), hematoxylin and eosin (HE) staining, TRAP staining, and immunohistochemistry, were conducted to observe bone tissue morphology, osteoclast differentiation, and the phosphorylation level of the PI3K-Akt-GSK3β signaling pathway. Results Transcriptomic and metabolomic data collectively reveal that the P2X7 receptor can impact the pathogenesis of osteoporosis through the PI3K-Akt-GSK3β signaling pathway. Subsequent in vitro experiments showed that cells in the Sh-P2X7 + Recilisib group exhibited increased proliferative activity (1.15 versus 0.59), higher absorbance levels (0.68 versus 0.34), and a significant increase in resorption pit area (13.94 versus 3.50). Expression levels of osteoclast differentiation-related proteins MMP-9, CK, and NFATc1 were markedly elevated (MMP-9: 1.72 versus 0.96; CK: 2.54 versus 0.95; NFATc1: 3.05 versus 0.95), along with increased fluorescent intensity of F-actin rings. In contrast, the OE-P2X7 + LY294002 group showed decreased proliferative activity (0.64 versus 1.29), reduced absorbance (0.34 versus 0.82), and a significant decrease in resorption pit area (5.01 versus 14.96), accompanied by weakened expression of MMP-9, CK, and NFATc1 (MMP-9: 1.14 versus 1.79; CK: 1.26 versus 2.75; NFATc1: 1.17 versus 2.90) and decreased F-actin fluorescent intensity. Furthermore, in vivo animal experiments demonstrated that compared with the wild type (WT) + Sham group, mice in the WT + OVX group exhibited significantly increased levels of CTX and NTX in serum (CTX: 587.17 versus 129.33; NTX: 386.00 versus 98.83), a notable decrease in calcium deposition (19.67 versus 53.83), significant reduction in bone density, increased trabecular separation, and lowered bone mineral density (BMD). When compared with the KO + OVX group, mice in the KO + OVX + recilisib group showed a substantial increase in CTX and NTX levels in serum (CTX: 503.50 versus 209.83; NTX: 339.83 versus 127.00), further reduction in calcium deposition (29.67 versus 45.33), as well as decreased bone density, increased trabecular separation, and reduced BMD. Conclusion P2X7 receptors positively regulate osteoclast formation and bone resorption by activating the PI3K-Akt-GSK3β signaling pathway.

Abstract To assess the concentration characteristics and ecological risks of potential toxic elements (PTEs) in water and sediment, 17 water samples and 17 sediment samples were collected in the Xiyu River to analyze the content of Cr, Ni, As, Cu, Zn, Pb, Cd and Hg, and the environmental risks of PTEs was evaluated by single-factor pollution index, Nemerow comprehensive pollution index, potential ecological risk, and human health risk assessment. The results indicated that Hg in water and Pb, Cu, Cd in sediments exceeded the corresponding environmental quality standards. In the gold mining factories distribution river section (X8-X10), there was a significant increase in PTEs in water and sediments, indicating that the arbitrary discharge of tailings during gold mining flotation is the main cause of PTEs pollution. The increase in PTEs concentration at the end of the Xiyu River may be related to the increased sedimentation rate, caused by the slowing of the riverbed, and the active chemical reactions at the estuary. The single-factor pollution index and Nemerow pollution index indicated that the river water was severely polluted by Hg. Potential ecological risk index indicated that the risk of Hg in sediments was extremely high, the risk of Cd was high, and the risk of Pb and Cu was moderate. The human health risk assessment indicated that As in water at point X10 and Hg in water at point X9 may pose non-carcinogenic risk to children through ingestion, and As at X8–X10 and Cd at X14 may pose carcinogenic risk to adults through ingestion. The average HQingestion value of Pb in sediments was 1.96, indicating that the ingestion of the sediments may poses a non-carcinogenic risk to children, As in the sediments at X8–X10 and X15–X17 may pose non-carcinogenic risk to children through ingestion.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC. Methods Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC–MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A. Results We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S–S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo. Conclusion The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents. Graphical Abstract The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of esophageal squamous cell carcinoma.

The annexins(ANX) family is widely present in the cell membrane, cytoplasm or extracellular matrix. As key tumor regulatory molecules, annexins A (ANX A) family can promote or inhibit invasion and metastasis of breast cancer cells by influencing cell membrane and cytoskeleton formation and participating in signaling pathways. ANX A family also plays a role in the apoptosis of breast cancer cells by regulation of pro-apoptotic proteins and cell cycle independent kinases (CDKs) and related pathways. In addition, ANX A family can also promote therapeutic resistance to a large number of drugs. For instance,ANX A1 enhances triple-negative breast cancer resistance by inducing epithelial-mesenchymal transformation. ANX A4 induces resistance by forming ANX A4-Fhit complexes and secretion of exosomes containing ANX A6 promotes paclitaxel resistance in breast cancer cells in a YAP1-dependent manner. So ANX A family may be a new target for breast cancer treatment.

Abstract The electrode played an essential role in the operation of CW-MFC system due to its synergistic effect, and the development of electrode strategy has promoted the application of CW-MFC since 2012. In this paper, according to the material and the quantity, the electrode types in CW-MFC were distinctly divided into unified model, composited model, modified model, and multi-electrodes model combined with non-conductive or conductive particle. Different electrode strategies were provided to improve the performance of CW-MFC towards electricity generation, removal of pollutants, and control of greenhouse gas emission, and the coordination mechanism was further reviewed. Furthermore, the development process of the electrode strategy was summarized, and the low-cost, sustainable, and innovated electrode materials were emphatically recommended. For the scale-up application, multi-electrode model was systematically reviewed based on the optimizing of the material, shape, spacing distance, and connection type of electrode. This review may provide guidance to maximize the advantages of CW-MFC applications. Graphical Abstract

Abstract The study specifically focused on the Hongliulin mining area, where a total of 40 soil samples were meticulously collected and analyzed from within a 1000 m radius extending from the tailings dam. The findings revealed that soil pH within the 0–1000 m range generally leaned towards the alkaline side. In terms of soil nutrient content, encompassing factors such as soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali nitrogen (AK), available phosphorus (AP), and quick-acting potassium (AK), the variations fell within the following ranges: 2.23–13.58 g/kg, 0.12–0.73 g/kg, 0.18–1.15 g/kg, 9.54–35.82 g/kg, 2.89–6.76 mg/kg, 3.45–11.25 mg/kg, and 5.86–130.9 mg/kg. Collectively, these values indicate relatively low levels of soil nutrients. Within the 0–500 m range of soil samples, the average concentrations of Cd, Hg, Pb, and As were 0.778, 0.198, 24.87, and 17.92 mg/kg, respectively. These concentrations exceeded the established soil background values of Shaanxi Province and emerged as the primary pollutants in the study area. Within this same range, the mean values of eight toxic metals (Pi) were ranked in the following descending order: 1.726 (Hg), 1.400 (As), 1.129 (Cr), 1.109 (Pb), 0.623 (Zn), 0.536 (Cd), 0.309 (Cu), and 0.289 (Ni). With the exception of Hg, As, Cr, and Pb, which exhibited slight pollution, the other toxic metals were found to be within acceptable pollution limits for this sampling range, in line with the results obtained using the geo-accumulation index method. The average potential ecological risk index for the eight toxic metals in the study area stood at 185.0, indicating a moderate overall pollution level. When assessing individual elements, the proportions of ecological risk attributed to Hg, As, Pb, and Cd were 34.57%, 27.44%, 25.11%, and 23.11%, respectively. This suggests that the primary potential ecological risk elements in the study area are Hg and As, followed by Cd and Pb. Notably, toxic metals Hg and Pb, as well as As and Pb, exhibited significant positive correlations within the sampling area, suggesting a common source. An analysis of the relationship between soil physicochemical properties and toxic metals indicated that soil pH, SOM, TN, and TP were closely linked to toxic metal concentrations. The toxic metal elements in the research area's soil exhibit moderate variability (0.16 0.36). Within the range of 0–200 m, the CV values for Cd and Hg exceed 1, indicating a high level of variability. The coefficient of variation for SOM, TP, AP, AK and TK is relatively high with the of 2.93, 2.36, 2.36, 21.01, 7.54. The soil in the sampling area has undergone significant disturbances due to human activities, resulting in toxic metal pollution and nutrient deficiencies.

The study aims to investigate the effect of ERAS (Enhanced Recovery After Surgery) management mode on functional exercise compliance and functional recovery after ACL (anterior cruciate ligament) reconstruction in males. Patients were admitted between June 2021 and December 2021 as the control group, and patients were admitted between January 2022 and June 2022 as the observation group. Routine nursing was adopted in the control group, while ERAS management mode was applied in the observation group for nursing. The clinical nursing efficacy, knee joint function (Lysholm score) and VAS (Visual analogue scale) score, patients’ functional training compliance and complications were compared. After intervention, the swelling disappearance time, pain disappearance time, hospital stay and other indicators of clinical nursing effect in the observation group were better (p < 0.05); the preoperative Lysholm score and VAS score showed no statistical significance (p > 0.05). The Lysholm score and VAS score at each time point after operation were markedly higher, and repeated measures analysis of variance manifested that the Lysholm score, VAS score, intergroup effect, time effect and interaction effect in both groups had statistical significance (p < 0.05). The total compliance rate of functional training in the observation group was conspicuously higher (p < 0.05); the overall incidence of complications in the observation group (13.3%) was evidently lower (28.7%) (p < 0.05). ERAS management mode can improve the functional training compliance, accelerate the recovery of joint function, reduce the incidence of complications and promote the quality of life of patients with ACL injury.

Accurately estimating the volume of woody vegetation is critical for assessing fuel characteristics and associated wildfire risks in shrublands. However, few studies have investigated the branch volume of multi-stemmed shrubs, a dominant life form in wildfire-prone drylands. This study predicts branch volume using the inflection point of branch diameter. This inflection point, identified using the “Segmented” package in R, marks the transition from a gradual decrease to a significant reduction in diameter along the stem. The volume of branch segment above this point is calculated as a cone, and below it, a cylinder. We validated this method on various species such as Caragana korshinskii, Salix psammophila, and Vitex negundo. Good estimations were achieved with an average 19.2% bias relative to reference branch volumes, outperforming conventional methods that subjectively treated the whole branch as either a cylinder (96.9% bias) or a cone (−34.4% bias). We tallied branches by basal diameter and provided inventories for easily locating the inflection point, as well as using two-way branch volume tables for rapid volume predictions in shrubland. In general, we developed an effective method for estimating branch volumes of multi-stemmed shrubs, enabling its application to larger-scale shrubland volumetric prediction. This advancement supports wildfire hazard assessment and informs decision-making in fuel treatments.

Proanthocyanidins (PAs), one of the most abundant natural polymers found in plants, are gaining increasing attention because of their beneficial effects for agriculture and human health. The study of PA biosynthesis has been active for decades, and progress has been drastically accelerated since the discovery of key enzymes such as Anthocyanidin Reductase (ANR), Leucoanthocyanidin Reductase (LAR), and key transcription factors such as Transparent Testa 2 (TT2) and Transparent Testa 8 (TT8) in the early 2000s. Scientists raised some compelling questions regarding PA biosynthesis about two decades ago in the hope that addressing these questions would lead to an enhanced understanding of PA biosynthesis in plants. These questions focus on the nature of starter and extension units for PA biosynthesis, the stereochemistry of PA monomers and intermediates, and how and where the polymerization or condensation steps work subcellularly. Here, I revisit these long-standing questions and provide an update on progress made toward answering them. Because of advanced technologies in genomics, bioinformatics and metabolomics, we now have a much-improved understanding of functionalities of key enzymes and identities of key intermediates in the PA biosynthesis and polymerization pathway. Still, several questions, particularly the ones related to intracellular PA transportation and deposition, as well as enzyme subcellular localization, largely remain to be explored. Our increasing understanding of PA biosynthesis in various plant species has led to a new set of compelling open questions, suggesting future research directions to gain a more comprehensive understanding of PA biosynthesis.

IntroductionThe components of nighttime sap flux (En), which include transpiration (Qn) and stem water recharge (Rn), play important roles in water balance and drought adaptation in plant communities in water-limited regions. However, the quantitative and controlling factors of En components are unclear.MethodsThis study used the heat balance method to measure sap flow density in Vitex negundo on the Loess Plateau for a normal precipitation year (2021) and a wetter year (2022).ResultsThe results showed that the mean values were 1.04 and 2.34 g h-1 cm-2 for Qn, 0.19 and 0.45 g h-1 cm-2 for Rn in 2021 and 2022, respectively, and both variables were greater in the wetter year. The mean contributions of Qn to En were 79.76% and 83.91% in 2021 and 2022, respectively, indicating that the En was mostly used for Qn. Although the vapor pressure deficit (VPD), air temperature (Ta) and soil water content (SWC) were significantly correlated with Qn and Rn on an hourly time scale, they explained a small fraction of the variance in Qn on a daily time scale. The main driving factor was SWC between 40-200 cm on a monthly time scale for the Qn and Rn variations. Rn was little affected by meteorological and SWC factors on a daily scale. During the diurnal course, Qn and Rn initially both declined after sundown because of decreasing VPD and Ta, and Qn was significantly greater than Rn, whereas the two variables increased when VPD was nearly zero and Ta decreased, and Rn was greater than Qn.DiscussionThese results provided a new understanding of ecophysiological responses and adaptation of V. negundo plantations to increasing drought severity and duration under climate changes.

Carbon emission efficiency and the ecological environment are key issues in achieving the United Nations Sustainable Development Goals. In this study, the three-stage epsilon-based measurement model and pressure-state-response model were used to calculate carbon emission efficiency and ecological environment index, and based on which, the coupling coordination model and panel vector autoregressive model were adopted to investigate the static coupling relationship and dynamic interaction. The results showed the following. (1) Carbon emission efficiency first decreased and then increased from 0.6633 to 0.7724, showing a decreasing spatial change pattern from east to west. (2) The ecological environment index increased from 0.4228 to 0.5993, showing a decreasing trend from the east and west to the center. (3) The state of the coupling coordination changed from barely coupling coordination to primary coupling coordination. Six provinces were high-level coupling coordination patterns promoted by the synergy of the two elements. (4) Ecological environment had a negative influence on carbon emission efficiency, showing time accumulation and buffering, whereas carbon emission efficiency could contribute to a steady and continuous improvement in ecological environment. This study provides an important reference for achieving carbon neutrality and enacting sustainable development.

Abstract Whilst early-life conditions have been understood to impact upon the health of older adults, further exploration of the field is required. There is a lack of consensus on conceptualising these conditions, and interpretation of experiences are socially and culturally dependent. To advance this important topic we invite authors to submit their research to the Collection on ‘The impact of early-life/childhood circumstances or conditions on the health of older adults’.

Abstract The social–ecological trap is an emerging concept that describes situations in which self‐reinforcing social and ecological feedbacks maintain or push a social–ecological system towards an undesirable state and threaten the sustainability of human societies. Understanding a system's feedback loops and identifying the leading factors of such traps is essential to develop effective management strategies to warn, avoid and escape traps. To better understand the dynamics of social–ecological traps, we developed a quantitative diagnostic framework that combines the social–ecological network approach and composite system state index. We demonstrated the effectiveness of the framework by examining the rural social–ecological evolution in China's Loess Plateau (LP) from 1949 to 2020, an area once faced with severe social–ecological challenges such as soil erosion, land degradation and poverty. Our analysis identified three stages of trap dynamics in LP: locked in the trap (1949–1981), reacting to the trap (1981–2003) and escaping the trap (2003–2020). In the first stage, LP was locked into an undesirable trajectory where reinforcing feedback occurs between rapid population growth, limited livelihood opportunities, excessive reliance on agriculture and severe soil erosion. Our results also found that the LP has made significant progress in escaping this social–ecological trap during the 21st century through ecological restoration practices and socioeconomic development. Similar social–ecological traps are also observed in many other regions of the world, particularly in developing countries. Our analysis recommends three pathways for addressing social–ecological traps in the LP: (1) promoting urbanization and livelihood diversity, (2) implementing site‐specific engineering measures (e.g. terraces and check dams in the LP) and (3) investing in ecological restoration programs. Escaping the trap is not the end of the story, but could be an early stage of another trap. Policymakers and managers should keep assessing and monitoring the policy practices and outcomes to avoid entering new trap situations. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Proanthocyanidins (PAs), flavonoid polymers involved in plant defense, are also beneficial to human health and ruminant nutrition. To date, there is little evidence for accumulation of PAs in maize (Zea mays), although maize makes anthocyanins and possesses the key enzyme of the PA pathway, anthocyanidin reductase (ANR). Here, we explore whether there is a functional PA biosynthesis pathway in maize using a combination of analytical chemistry and genetic approaches. The endogenous PA biosynthetic machinery in maize preferentially produces the unusual PA precursor (+)-epicatechin, as well as 4β-(S-cysteinyl)-catechin, as potential PA starter and extension units. Uncommon procyanidin dimers with (+)-epicatechin as starter unit are also found. Expression of soybean (Glycine max) anthocyanidin reductase 1 (ANR1) in maize seeds increases the levels of 4β-(S-cysteinyl)-epicatechin and procyanidin dimers mainly using (-)-epicatechin as starter units. Introducing a Sorghum bicolor transcription factor (SbTT2) specifically regulating PA biosynthesis into a maize inbred deficient in anthocyanin biosynthesis activates both anthocyanin and PA biosynthesis pathways, suggesting conservation of the PA regulatory machinery across species. Our data support the divergence of PA biosynthesis across plant species and offer perspectives for future agricultrural applications in maize.

Abstract Background Acute myocardial infarction (AMI) is a main cause of death all around the world. There is a close relationship between myocardial infarction (MI) and depression. MI patients with untreated depression had higher mortality than those without depression. Therefore, this study aimed to explore the effect of escitalopram in treating a model under MI and unpredictable chronic mild stress (UCMS). Methods Male C57BL/6J mice were treated with sham surgery, or MI surgery, or UCMS, or escitalopram (ES) for a consecutive two weeks. And the mice were divided into Sham group, MI group, MI + UCMS group, MI + UCMS + ES group (n = 8 in each group). After treatment, the mice went through open field test for anxiety behavior, sucrose preference test for depressive behavior. After sacrificed, the blood, heart, hippocampus, and cortex were collected. Results The escitalopram badly increased the area of cardiac fibrosis size. The sucrose preference test demonstrated that escitalopram treatment showed significant effect in improving depressive behaviors of mice under MI + UCMS. The potential mechanism involved the interrelation between 5-HT system and inflammation. MI significantly affected the level of cardiac SERT. Both UCMS and ES significantly affected the level of cortex TNF-α. UCMS significantly affected the level of cardiac IL-33. In the hippocampus tissue, TNF-α was positively correlated with SERT, and IL-10 was positively correlated with SERT. In the cortex tissue, IL-33 was positively correlated with 5-HT4R, and sST2 was positively correlated with 5-HT. Conclusions Two-week escitalopram treatment might worsen myocardial infarction. But escitalopram could benefit depressive behaviors, which may be related with the interrelationship between the 5-HT system and inflammatory factors in the brain.

Abstract Background Many studies have found that engaging in activities, including physical exercise, social interaction, and cognitive training, is beneficial for preventing cognitive decline among older adults; however, the demographic differences in the association between activity engagement and cognitive functions remain understudied. This study investigates: (a) the influence of activity engagement on cognitive functions among Chinese older adults, and (b) the moderating roles of age and gender in these associations . Methods The data were derived from the China Health and Retirement Longitudinal Study in 2018, which included 9803 participants aged 60 or older. A multiple regression model was used to test the study hypotheses. Results Engaging in physical activity (b = 1.578, p

ABSTRACTThe interaction between adherent-invasive Escherichia coli (AIEC) and intestinal macrophages is implicated in the pathogenesis of Crohn’s disease (CD). However, its role in intestinal fibrogenesis and the underlying molecular mechanisms are poorly understood. In addition, miRNAs such as let-7b may participate in AIEC-macrophage interactions. In this study, we identified that the colonization of AIEC in the ileum was associated with enhanced intestinal fibrosis and reduced let-7b expression by enrolling a prospective cohort of CD patients undergoing ileocolectomy. Besides, AIEC-infected IL-10−/− mice presented more severe intestinal fibrosis and could be improved by exogenous let-7b. Mechanistically, intestinal macrophages were found to be the main target of let-7b. Transferring let-7b-overexpressing macrophages to AIEC-infected IL-10−/− mice significantly alleviated intestinal fibrosis. In vitro, AIEC suppressed exosomal let-7b derived from intestinal epithelial cells (IECs), instead of the direct inhibition of let-7b in macrophages, to promote macrophages to a fibrotic phenotype. Finally, TGFβR1 was identified as one target of let-7b that regulates macrophage polarization. Overall, the results of our work indicate that AIEC is associated with enhanced intestinal fibrosis in CD. AIEC could inhibit exosomal let-7b from IECs to promote intestinal macrophages to a fibrotic phenotype and then contributed to fibrogenesis. Thus, anti-AIEC or let-7b therapy may serve as novel therapeutic approaches to ameliorate intestinal fibrosis.

Water security is the backbone of regional development. However, it is generally compromised by the increasing competition for water resources between natural and social systems, especially in areas with limited water resources. Sustainable water planning requires a comprehensive analysis of supply and demand patterns, which is difficult owing to scale mismatches in data and methodologies. This study investigated the dynamics and interrelationships of water supply and demand in a semi-arid watershed of the Loess Plateau, China, by developing a system dynamics model that simulates water security during 1980–2020 and future changes under different climate, socioeconomic development, and inter-basin water diversion scenarios during 2021–2050. The results showed that (1) by the end of 2020, the regional water security level gradually approached the water scarcity threshold indicated by the water deficit index surpassing 0; (2) under unfavorable climate and progressive socioeconomic growth conditions, up to 16 out of 30 years of simulation demonstrated water insecurity in the form of a net water quantity deficit; and (3) the water diversion project can offset such deficits in the short term, but potentially aggravates water insecurity risk by eliciting a more rapid socioeconomic growth pattern. The results indicate that curbing demand and improving water-saving technology are instructive in water resource management. For the Yanhe Watershed, the quantity and pattern of water diversion should be improved in the future to guarantee water resource security on a full temporal scale. We suggest a moderate socioeconomic growth rate to be more appropriate for this region and that efforts to solidify water use redlines and advancement in water-saving technologies are essential in the future. This study provides a scientific basis for the long-term evaluation of regional water security on a full timescale with tightly coupled hydrological components and a modeling framework for decision-makers to manage water resources sustainably.

Background & Aims: Gamma delta (γδ) T cells are heterogeneous and functionally committed to producing interferon (IFN)-γ and interleukin (IL)-17. γδT cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17–producing γδT cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A+ γδT cells is lacking. Methods: We undertook a single-cell analysis of γδT17 cells derived from murine livers. A parabiosis model was used to assess tissue residency. Fluorescence-activated cell sorting and adoptive transfer experiments were used to investigate the response and protective role of liver-resident CD44hiCD27− γδT cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44hiCD27− γδT cells. Results: We identified hepatic IL-17A–producing γδT cells as CD44hiCD27− γδT cells. They had tissue-resident characteristics and resided principally within the liver. Vγ6+ T cells also exhibited liver-resident features. Liver-resident CD44hiCD27− γδT cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44hiCD27− γδT cells could produce IL-17A and IFN-γ simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44hiCD27− γδT cells into Lm-infected TCRδ−/− mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44hiCD27− γδT cells into infection sites. Conclusions: Liver-resident CD44hiCD27− γδT cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44hiCD27− γδT cells and contribute to the clearance of Lm at the early stage of infection corporately.

(1) Background: polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome with a constellation of cardiometabolic risk factors. We aimed to investigate if the association of body fat mass (BFM) and skeletal muscle mass (SMM) with cardiometabolic risk differed in PCOS subtypes. (2) Methods: 401 participants (245 PCOS and 156 controls) were assessed for anthropometric measurements, glucose–lipid profiles, reproductive hormones and body composition with propensity score-matched (PSM) analysis. The association of the cardiometabolic risk score (z score, calculated based on levels of obesity and gluco-lipid measurements) with BFM (estimated by trunk BFM/Height2) and SMM (estimated by SMM/Height2) was calculated. (3) Results: Trunk BFM/Height2 and SMM/Height2 were both positively associated with cardiometabolic risk in PCOS (trunk BFM/Height2, OR 2.33, 95% CI 1.49–3.65; SMM/Height2, OR 2.05, 95% CI 1.12–3.76). SMM/Height2 associated with increased cardiometabolic risk in obese PCOS (BMI ≥ 28 kg/m2, OR 2.27, 95% CI 1.15–4.47). For those with lower BMI (2), trunk BFM/Height2 showed a higher OR in both groups (PCOS, OR 2.12, 95% CI 1.06–4.24; control 2.04, 95% CI 1.04–4.02). Moreover, distinct associations among BMI-stratified groups were validated in hierarchical clustering identifying metabolic and reproductive clusters. (4) Conclusions: BFM and SMM are synergistically associated with higher cardiometabolic risk in PCOS women. Although BFM contributes to increased cardiometabolic risk, SMM also plays a primary role in obese PCOS. Our results highlight the importance of body composition in the management of PCOS.

The Beijing–Tianjin–Hebei region in China is experiencing a serious ecological water scarcity problem in the context of climate warming and drying. There is an urgent need for practical adaptation measures to cope with the adverse impacts of climate change and provide a scientific basis for urban water supply planning, water resource management, and policy formulation. Urban ecological water can maintain the structure and function of urban ecosystems, both as an environmental element and as a resource. Current research lacks quantitative analysis of the impact of regional meteorological factors on ecological water use at the small and medium scales. Based on the meteorological data and statistical data of water resources in the Beijing–Tianjin–Hebei (BTH) region, this paper analyzed the trend of climate change and established an ecological climatic water model using gray correlation analysis, polynomial simulation, and singular spectrum analysis to predict the ecological water consumption. And, we assessed the climatic sensitivity of ecological water use and estimated the future ecological climatic water use in the BTH region based on four climate scenarios’ data. The results showed that the average multi-year temperature was 13.2 °C with a clear upward trend from 1991 to 2020 in the BTH region. The multi-year average precipitation was 517.1 mm, with a clear shift in the period of abundance and desiccation. Ecological climatic water modeling showed that a 1 °C increase in temperature will increase ecological water use by 0.73 × 108 m3~1.09 × 108 m3 in the BTH region; for a 100 mm increase in precipitation, ecological water use will decrease by 0.49 × 108 m3~0.88 × 108 m3; under the four climate scenarios of SSP1–2.6, SSP2–4.5, SSP3–7.0, and SSP5–8.5, the regional ecological climatic water use will be 5.14 × 108 m3, 6.64 × 108 m3, 7.82 × 108 m3, and 9.06 × 108 m3 in 2035, respectively; and in 2050, the ecological climatic water use will be 8.16 × 108 m3, 9.75 × 108 m3, 10.71 × 108 m3, and 12.41 × 108 m3, respectively. The methodology and results of this study will support the quantification of climate change impacts on ecological water use in the BTH region and serve as a theoretical basis for future research on ecological water use adaptation to climate change. This study can provide a basis for the development of the overall planning of urban ecological water supply, and at the same time, it can lay a foundation for the study of measures to adapt to climate change by ecological water use.

IntroductionLaboratory teaching of medical microbiology involves highly pathogenic microorganisms, thus posing potential biosafety risks to the students and the teacher. To address these risks, non/low-pathogenic microorganisms were modified to mimic highly pathogenic ones or highly pathogenic microorganisms were attenuated directly using the CRISPR/Cas9 technology. This study describes the modification of Escherichia coli DH5α to mimic Shigella and its evaluation as a safe alternative for medical laboratory teaching.MethodsTo generate E. coli DH5α△FliC△tnaA2a, the tnaA and FliC genes in E. coli DH5α were knocked out using CRISPR/Cas9 technology; a plasmid bearing the O-antigen determinant of S. flexneri 2a was then constructed and transformed. Acid tolerance assays and guinea pig eye tests were used to assess the viability and pathogenicity, respectively. Questionnaires were used to analyze teaching effectiveness and the opinions of teachers and students.ResultsThe survey revealed that most teachers and students were inclined towards real-time laboratory classes than virtual classes or observation of plastic specimens. However, many students did not abide by the safety regulations, and most encountered potential biosafety hazards in the laboratory. E. coli DH5α△FliC△tnaA2a was biochemically and antigenically analogous to S. flexneri 2a and had lower resistance to acid than E. coli. There was no toxicity observed in guinea pigs. Most of teachers and students were unable to distinguish E. coli DH5α△FliC△tnaA2a from pure S. flexneri 2a in class. Students who used E. coli DH5α△FliC△tnaA2a in their practice had similar performance in simulated examinations compared to students who used real S. flexneri 2a, but significantly higher than the virtual experimental group.DiscussionThis approach can be applied to other high-risk pathogenic microorganisms to reduce the potential biosafety risks in medical laboratory-based teaching and provide a new strategy for the development of experimental materials.

IntroductionRainfall events can determine a cascade of plant physiological and ecological processes, and there is considerable interest in the way that rainfall modifies plant water flux dynamics.MethodsThe sap flow density (SF) of the planted species of Vitex negundo and Hippophae rhamnoides, on the Loess Plateau of China was monitored using the heat balance method from 2015 to 2017.Results and discussionThe results showed that SF responded differently to rainfall classes because of the changing meteorological and soil water content (SWC) conditions. For class 1: 0.2–2 mm, SF increased by 14.36–42.93% for the two species, which were mainly attributable to the effect of solar radiation and vapor pressure deficit after rainfall. For class 2: 2–10 mm, SF remained nearly stable for V. negundo and decreased for H. rhamnoides because of the relative humidity’s effect. For class 3: > 10 mm, SF increased significantly because of increased SWC and the increasing response to solar radiation. The increased percentage of SF was relatively higher for V. negundo when rainfall was less than 20 mm, while the value was higher for H. rhamnoides when rainfall was greater than 10 mm. Further, V. negundo’s water potential increased at the soil–root interface (ψ0) and ψL, indicating that the plant, which has shallower roots and a coarser of leaf and bark texture, considered as anisohydric species and used precipitation-derived upper soil water to survive. The relatively consistent ψL and ψ0 for H. rhamnoides, which has deep roots and leathery leaves, indicated that this species was considered as isohydric species and insensitive to the slight change in the soil water status. The differed response patter and water use strategies between the two species showed that species as V. negundo are more susceptible to frequent, but small rainfall events, while larger, but less frequent rainfall events benefit such species as H. rhamnoides. This study quantified the effect of environmental factors for SF variation. The results could help formulate a selection process to determine which species are more suitable for sustainable management in the afforestation activities under the context of more frequent and intense rainfall events.

Abstract Background Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined. Methods Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin–neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5′-untranslated region (5′-UTR)-mediated translation was analyzed using a dual luciferase reporter system. Conclusion We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5′-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5′-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA, and involved in various biological processes in plants. However, the distribution features and functions of mRNA m6A methylation have been poorly explored in woody perennial plants. In this study, a new natural variety with yellow-green leaves, named Maiyuanjinqiu, was screened from the seedlings of Catalpa fargesii. Based on the preliminary experiment, the m6A methylation levels in the leaves of Maiyuanjinqiu were significantly higher than those in C. fargesii. Furthermore, a parallel analysis of m6A-seq and RNA-seq was carried out in different leaf color sectors. The result showed that m6A modification were mostly identified around the 3’-untranslated regions (3’-UTR), which was slightly negatively correlated with the mRNA abundance. KEGG and GO analyses showed that m6A methylation genes were associated with photosynthesis, pigments biosynthesis and metabolism, oxidation-reduction and response to stress, etc. The overall increase of m6A methylation levels in yellow-green leaves might be associated with the decreased the expression of RNA demethylase gene CfALKBH5. The silencing of CfALKBH5 caused a chlorotic phenotype and increased m6A methylation level, which further confirmed our hypothesis. Our results suggested that mRNA m6A methylation could be considered as a vital epigenomic mark and contribute to the natural variations in plants.

As a plant-specific transcription factor, the SPL gene family plays a critical role in plant growth and development. Although the SPL gene family has been identified in diverse plant species, there have been no genome-wide identification or systematic study reports on the SPL gene family in Catalpa bungei. In this study, we identified 19 putative SPL gene family members in the C. bungei genome. According to the phylogenetic relationship, they can be divided into eight groups, and the genes in the same group have a similar gene structure and conserved motifs. Synteny analysis showed that fragment duplication played an important role in the expansion of the CbuSPL gene family. At the same time, CbuSPL genes have cis-acting elements and functions related to light response, hormone response, growth and development, and stress response. Tissue-specific expression and developmental period-specific expression analysis showed that CbuSPL may be involved in flowering initiation and development, flowering transition, and leaf development. In addition, the ectopic expression of CbuSPL4 in Arabidopsis confirmed that it can promote early flowering and induce the expression of related flowering genes. These systematic research results will lay a foundation for further study on the functional analysis of SPL genes in C. bungei.

Abstract This study examined the mediator role of social capital on the association between perceived neighborhood environment and life satisfaction among older adults in urban China, and further tested the moderating effect of gender in the above paths (i.e., from neighborhood environment to life satisfaction; from neighborhood environment to social capital; from social capital to life satisfaction). We used quota sampling approach to recruit 472 respondents aged 60 years old or older in Shanghai in 2020. From the perspective of structural equation modeling, multiple group analysis was conducted to examine the proposed hypotheses. The measurement model of social capital was well established in urban Chinese community contexts. Based on the whole sample, the results of the mediation model showed that social capital played a mediation role in the association between neighborhood environment and life satisfaction. Furthermore, the results of multiple group analysis showed that the association between neighborhood environment and cognitive social capital was only significant among older women. The findings highlight the role of neighborhood environment and social capital in building age-friendly communities.

The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment, and on this basis, to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation. The titer of human parainfluenza virus type 3 (HPIV3), Autographacaliforinica nuclear polyhedrosis virus carried a green fluorescent reporter gene (AcNPV-GFP) and Enterovirus group D 68 (EV-D68) were determined by plaque assays or TCID50 methods after treatment by MB combined with illumination (MB photochemical, MBP) or ultrasonic excitation. Different ultrasonic power and time, MB concentration gradient were set to determine the best anti-viral combination. For the enveloped virus HPIV3 and AcNPV-GFP, pure ultrasonic or MBP treatment could reduce viral titer more than 104，and ultrasonic combined with MB could completely inactivate HPIV3 and AcNPV-GFP in 5min while traditional MBP methods could only reduce viral titer about 10X. For the non-enveloped virus EV-D68, pure ultrasonic or MBP treatment only reduced the viral titer about 102, but ultrasonic combined with MB treatment could reduce the viral titer about 103 in 5min and completely inactive EV-D68 in 10min (reduced 105). Compared with MBP method and pure ultrasonic inactivation, ultrasonic combined with MB has better inactivation effect on either enveloped or non-enveloped viruses, and the appropriate combination of parameters is expected to be a new blood transfusion transmitted virus inactivation method.

DnaJs are the common molecular chaperone proteins with strong structural and functional diversity. In recent years, only several DnaJ family members have been found to be able to regulate leaf color, and it remains to be explored whether there are other potential members that also regulate this character. Here, we identified 88 putative DnaJ proteins from Catalpa bungei, and classified them into four types according to their domain. Gene-structure analysis revealed that each member of CbuDnaJ family had same or similar exon-intron structure. Chromosome mapping and collinearity analysis showed that tandem and fragment duplication occurred in the process of evolution. Promoter analyses suggested that CbuDnaJs might be involved in a variety of biological processes. The expression levels of DnaJ family members in different color leaves of Maiyuanjinqiu were respectively extracted from the differential transcriptome. Among these, CbuDnaJ49 was the largest differentially expressed gene between the green and yellow sectors. Ectopic overexpression of CbuDnaJ49 in tobacco showed that the positive transgenic seedlings exhibited albino leaves, and the contents of chlorophyll and carotenoid were significantly reduced compared with those of wild type. The results suggested that CbuDnaJ49 played an important role in regulating leaf color. This study not only identified a novel gene of DnaJ family members regulating leaf color, but also provided new germplasm for landscaping.

BackgroundDrug resistance is a prominent problem in the treatment of tuberculosis, so it is urgent to develop new anti- tuberculosis drugs. Here, we investigated the effects and mechanisms of cisplatin (DDP) on intracellular Mycobacterium smegmatis to tap the therapeutic potential of DDP in mycobacterial infection.ResultsMacrophages infected with Mycobacterium smegmatis were treated with DDP alone or combined with isoniazid or rifampicin. The results showed that the bacterial count in macrophages decreased significantly after DDP (≤ 6 μg/mL) treatment. When isoniazid or rifampicin was combined with DDP, the number of intracellular mycobacteria was also significantly lower than that of isoniazid or rifampicin alone. Apoptosis of infected cells increased after 24 h of DDP treatment, as shown by flow cytometry and transmission electron microscopy detection. Transcriptome sequencing showed that there were 1161 upregulated and 645 downregulated differentially expressed genes (DEGs) between the control group and DDP treatment group. A Trp53-centered protein interaction network was found based on the top 100 significant DEGs through STRING and Cytoscape software. The expression of phosphorylated p53, Bax, JAK, p38 MAPK and PI3K increased after DDP treatment, as shown by Western blot analysis. Inhibitors of JAK, PI3K or p38 MAPK inhibited the increase in cell apoptosis and the reduction in the intracellular bacterial count induced by DDP. The p53 promoter Kevetrin hydrochloride scavenges intracellular mycobacteria. If combined with DDP, Kevetrin hydrochloride could increase the effect of DDP on the elimination of intracellular mycobacteria. In conclusion, DDP at low concentrations could activate the JAK, p38 MAPK and PI3K pathways in infected macrophages, promote the phosphorylation of p53 protein, and increase the ratio of Bax to Bcl-2, leading to cell apoptosis, thus eliminating intracellular bacteria and reducing the spread of mycobacteria.ConclusionDDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.

BackgroundThe Enterovirus D68 (EV-D68) epidemic has increased knowledge of the virus as a pathogen capable of causing serious respiratory and neurological illnesses. It has been shown that long noncoding RNAs (lncRNAs) regulate viral replication and infection via multiple mechanisms or signaling pathways. However, the precise function of lncRNAs in EV-D68 infection remains unknown.MethodsThe differential expression profiles of lncRNA in EV-D68-infected and uninfected rhabdomyosarcoma (RD) cells were studied using high-throughput sequencing technology. The knockdown through small interfering RNA (siRNA) and overexpression of lncRNA SNHG9 (small ribonucleic acid host gene 9) were applied to investigate how lncRNA SNHG9 regulates EV-D68 propagation. The targeted interactions of lncRNA SNHG9 with miR-150-5p and miR-150-5p with c-Fos were validated using dual luciferase reporter system. LncRNA SNHG9 knockdown and miR-150-5p inhibitor were co-transfected with RD cells. QRT-PCR and western blot were used to detect RNA and protein levels, of c-Fos and VP1, respectively. Median tissue culture infectious dose (TCID50) was applied to detect viral titers.ResultsThe results demonstrated that a total of 375 lncRNAs were highly dysregulated in the EV-D68 infection model. In the EV-D68 infection model, lncRNA SNHG9 and c-Fos were increased in EV-D68-infected RD cells. However, the expression level of miR-150-5p was downregulated. In addition, overexpression of SNHG9 in RD cells resulted in decreased viral replication levels and viral titers following infection with EV-D68, and further experiments revealed that overexpression of SNHG9 inhibited the viral replication by targeting increased miR-150-5p binding and significantly increased c-Fos expression in RD cells.ConclusionOur findings indicate that the SNHG9/miR-150-5p/c-Fos axis influences EV-D68 replication in host cells and that SNHG9 may be a possible target for anti-EV-D68 infection therapies.

Soil salinity is well known heterogeneous and various within natural soil environment. In Songnen grassland of Northeast China, grazing aggravates the saline-alkali heterogeneity in soil habitat, which led to dominant clonal plant species forming a variety of adaptive strategies. However, based on the previous studies of morphological plasticity and clonal integration in clonal plants, there was a lack of mechanism research on the spatial expansion strategy of clonal plants population subjected to clipping in saline-alkali heterogeneity soil patches. To address this knowledge gap, we carried out an experiment by applying different clipping intensities (0%, 35%, 70% of the above-ground biomass removed) to explore the spatial expansion strategy and morphological plasticity of Leymus chinensis and their belowground rhizomes in different heterogeneous saline-alkali patches. We found that, clipping significantly decreased the plant average height and above-ground biomass in homogeneous patches, especially heavy clipping had a significant adverse impact on plant belowground (rhizome, fine root) biomass and leaf area. However, there was no significant difference in the biomass, average height, and leaf area among the clipping treatments in low saline-alkali heterogeneous patches. In addition, the number of leaves, daughter plants and rhizome internode buds were significantly affected by saline-alkali heterogeneity alone, and low saline-alkali heterogeneity had a positive effect on these parameters. Biomass accumulation and rhizome expansion were gradually inhibited by the increasing of clipping intensity in a homogeneous environment, but the inhibitory effect of clipping was not significant in saline-alkali patches soil. We concluded that L. chinensis can respond to grazing or mowing disturbance by increasing tiller and daughter-plant numbers in a saline-alkali heterogeneous environment. The saline-alkali patches promoted clonal plant population spatial expansion more than grazing or mowing disturbance did. This study emphasizes saline-alkali heterogeneity distribution patterns in grassland soil environment were the primary and important driving factor promoting the spatial expansion of L. chinensis.

Background: Myocardial infarction (MI) induces high morbidity all over the world. Patients with MI are more vulnerable to depression, and depression worsens their prognosis. Inflammatory response is the primary pathophysiological mechanism of MI combined with depression. Therefore, MI and depression would benefit from attenuating inflammation. Objectives: To explore the anti-inflammation effect in relieving heart dysfunction and depressive behaviors of mice under MI and chronic stress. Materials and Methods: A total of 40 male C57BL/6J mice were given sham or MI surgery, and the success rate of the surgery was 80%. Hence, 32 mice survived surgery and were distributed as 8 in each group of study. Then, unpredictable chronic mild stress (UCMS) or Anshen Buxin Liuwei pills (ABL pills) group were applied to some MI mice, and the mice were divided into different groups, including sham group, MI group, MI + UCMS group, and MI + UCMS + ABL pills group (n = 8). After a 2-week treatment, the mice underwent the sucrose preference test, and echocardiography before sacrifice. Then, the mice were sacrificed for pathological detection and inflammatory cytokines detection. Results: Compared with mice in the sham group, those mice had lower left ventricular ejection fraction (LVEF) (51.25 ± 9.92 vs. 12.18 ± 8.46, 20.95 ± 16.40, 29.55 ± 13.33%, P < 0.05) and left ventricular fractional shortening (LVFS) (21.12 ± 6.82 vs. 5.57 ± 4.0, 9.89 ± 8.03, 14.0 ± 6.65%, P < 0.05) in the MI, MI + UCMS, and MI + UCMS + ABL pills groups. ABL pills could reverse cardiac dysfunction for the significant elevation of LVEF and LVFS. The hematoxylin and eosin staining presented left ventricular (LV) enlargement, inflammatory cell infiltration, and myocardial fibrosis formation in MI and MI + UCMS mice. While ABL pills reversed the pathological changes induced by ligation of the left anterior descending. The enzyme-linked immunosorbent assay detection showed that MI and MI + UCMS elevated the concentrations of cardiac tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1), which were reduced by ABL pills. ABL pills significantly reversed the depressive behaviors of mice with MI + UCMS (82.97 ± 3.04 vs. 76.07 ± 7.84%, P < 0.05). MI + UCMS group had a higher level of cortex TNFR1 than sham and MI, while ABL pills reversed the elevation (P > 0.05). Conclusions: Anti-inflammation treatment effectively improves cardiac function and depressive behaviors via inhibiting TNF-α/TNFR1.

Abstract Background Dizziness and vertigo are common clinical symptoms. Gastrodin injection has shown clinical effects on dizziness or vertigo. However, little is known about the effectiveness and costs of combining Gastrodin injection with conventional treatment on dizziness or vertigo in daily practice. This study aimed to analyze the clinical and economic effects of Gastrodin injection for patients with dizziness or vertigo in comparison to Extract of Ginkgo Biloba Leaves injection in real-world practice. Methods Data was collected from the Hospital Information System of 131 hospitals across China from January to December 2018. Patients whose primary discharge diagnosis was dizziness or vertigo according to ICD-10 diagnostic coding were included and divided into two samples: sample of dizziness or vertigo; sample of dizziness or vertigo, with the complication of cerebral infarction. Comparative analysis of the medical cost per hospitalization, hospitalization duration, effective rates, and cure rates between the group of Gastrodin injection and the group of Extract of Ginkgo Biloba Leaves injection was conducted. Propensity Score Matching was used to control potential confounding factors. Results In the sample of dizziness or vertigo, although there was no significant differences on hospitalization duration (P = 0.080), the group of Gastrodin injection was significantly better than the group of Extract of Ginkgo Biloba Leaves injection (P

Abstract Background While depressive symptoms are recognized as major mental health problems in later life, there is a lack of study in examining potential moderators in the association between intergenerational support and depressive symptoms, especially in social contexts with low socioeconomic status and inadequate formal public support. This study set out to examine the association between intergenerational support and depressive symptoms among older adults in rural Northeast China, and the potential moderating roles of age, living alone, and number of chronic diseases on this link. Methods A quota sampling approach was used to recruit 448 respondents aged 60 and above from rural Chinese communities. Depressive symptoms were the dependent variable. Intergenerational emotional, instrumental, and financial support were the main independent variables. Age, living alone, and number of chronic diseases were the moderators. Multiple linear regression models with interaction terms were conducted to test the proposed model. Results The results showed that intergenerational emotional support was significantly associated with depressive symptoms in older adults when instrumental and financial support and covariates were controlled (β = -0.196, p < .001). Age was found to have a significant moderating effect on the relationship between intergenerational instrumental support and depressive symptoms (β = -0.118, p < .05). Among older respondents aged 74.51 years and older, instrumental support was positively associated with depressive symptoms, but this association was not significant for younger respondents. Furthermore, living alone and number of chronic diseases suffered moderated the association between intergenerational financial support and depressive symptoms, which was statistically significant only for those living alone and with more chronic diseases (interaction term between living alone and intergenerational financial support: β = -0.082, p < .05; interaction term between number of chronic diseases and intergenerational financial support: β = -0.088, p < .05. Conclusions The findings not only highlight the important role of intergenerational support in promoting mental health in later life in rural Chinese contexts, but also identify within-population heterogeneity in the identified associations. Policy and intervention implications are discussed.

Abstract Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2–6 microns (1–2 pixels) for healthy subjects and 3–10 microns (1–3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.

Root rot caused by Fusarium oxysporum is a serious root disease that affects the growth and yield of peanut crops worldwide. Identifying resistance genes is of great significance for both conventional and molecular breeding. At present, there are a few identified disease resistance genes, and the defense response mechanism against this pathogen remains unclear. Using transcriptome analysis techniques, 21 differentially expressed genes (DEGs) were identified in plants treated with Bacillus thuringiensis TG5 and carbendazim. Among these DEGs, the TIFY10A protein gene, pyruvate decarboxylase, and UDP glycosyltransferase 74B1 genes play an important role in early resistance to root rot in peanut plants, leading to regulatory factors that trigger immunity. Our study provides important information on the response mechanism of peanut plants to F. oxysporum-induced root rot and the protective benefits of colonization by the microbial pesticide, B. thuringiensis.

Abstract Background With the advancement of sequencing technologies, a plethora of noncoding RNA (ncRNA) species have been widely discovered, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs). However, the mechanism of these non-coding RNAs in diseases caused by enterovirus d68 (EV-D68) remains unclear. The goal of this research was to identify significantly altered circRNAs, lncRNAs, miRNAs, and mRNAs pathways in RD cells infected with EV-D68, analyze their target relationships, demonstrate the competing endogenous RNA (ceRNA) regulatory network, and evaluate their biological functions. Methods The total RNAs were sequenced by high-throughput sequencing technology, and differentially expressed genes between control and infection groups were screened using bioinformatics method. We discovered the targeting relationship between three ncRNAs and mRNA using bioinformatics methods, and then built a ceRNA regulatory network centered on miRNA. The biological functions of differentially expressed mRNAs (DEmRNAs) were discovered through GO and KEGG enrichment analysis. Create a protein interaction network (PPI) to seek for hub mRNAs and learn more about protein–protein interactions. The relative expression was verified using RT-qPCR. The effects of Fos and ARRDC3 on virus replication were confirmed using RT-qPCR, virus titer (TCID50/ml), Western blotting. Results 375 lncRNAs (154 upregulated and 221 downregulated), 33 circRNAs (32 upregulated and 1 downregulated), 96 miRNAs (49 upregulated and 47 downregulated), and 239 mRNAs (135 upregulated and 104 downregulated) were identified as differently in infected group compare to no-infected group. A single lncRNA or circRNA can be connected with numerous miRNAs, which subsequently coregulate additional mRNAs, according to the ceRNA regulatory network. The majority of DEmRNAs were shown to be connected to DNA binding, transcription regulation by RNA polymerase II, transcription factor, MAPK signaling pathways, Hippo signal pathway, and apoptosis pathway, according to GO and KEGG pathway enrichment analysis. The hub mRNAs with EGR1, Fos and Jun as the core were screened through PPI interaction network. We preliminarily demonstrated that the Fos and ARRDC3 genes can suppress EV-D68 viral replication in order to further verify the results of full transcriptome sequencing. Conclusion The results of whole transcriptome analysis after EV-D68 infection of RD cells were first reported in this study, and for the first time, a ceRNA regulation network containing miRNA at its center was established for the first time. The Fos and ARRDC3 genes were found to hinder viral in RD cells. This study establishes a novel insight host response during EV-D68 infection and further investigated potential drug targets.

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14 ARF , p15 INK4b and p16 INK4a ) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

Abstract Background With the increasing production and use of ethylene oxide (EO) worldwide, its explicit bio-toxicity has drawn more and more attention. At present, most studies focus on chronic EO exposure. Studies on acute EO exposure are rare, especially with imaging studies. To our knowledge, this work is the first documented case of reversible cerebral vasoconstriction syndrome (RCVS) with cerebral infarction caused by EO. Case presentation A 58-year-old woman who worked in a capsule production factory got an unprotected acute EO inhalation due to accidental exposure to sterilization gas. She suffered from nausea, vomiting, and severe paroxysmal headaches, but the first brain MRI scan of the patient showed no significant abnormality. Nine days after inhalation, she developed recurrent thunderclap headaches and gradual complete blindness. The follow-up brain MRI, 12 days after inhalation, demonstrated extensive cytotoxic edema. Fifteen days and 21 days after EO (ethylene oxide) inhalation, head MRA and CTA respectively showed diffuse vasoconstriction of cerebral arteries. Fifty-nine days after EO inhalation, head MRA assessed reversibility of the vasoconstriction. According to clinical features and imaging findings, RCVS with cerebral infarction can be diagnosed. The patient was sensitive to light and light reflection but still blind after symptomatic and rehabilitation therapy. Conclusions We report an acute EO exposure case in which the patient suffered from RCVS with cerebral infarction, which previous literature has not reported. This article aimed to raise awareness of encephalopathy after EO acute exposure.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate and presents a major challenge for human health. Activation of multiple oncogenes has been reported to be strongly associated with the progression of HCC. Moreover, the immunosuppressive tumor microenvironment (TME) and the host immune system are also implicated in the development of malignant HCC tumors. Glypican-3 (GPC-3), a proteoglycan involved in the regulation of cell proliferation and apoptosis, is aberrantly expressed in HCC. We synthesized a short 5ʹ-triphosphate (3p) RNA targeting GPC-3, 3p-GPC-3 siRNA, and found that it effectively inhibited subcutaneous HCC growth by raising type I IFN levels in tumor cells and serum and promoting tumor cell apoptosis. Moreover, 3p-GPC-3 siRNA was able to enhance the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells while reducing the proportion of regulatory T cells (Tregs) in the TME. Most intriguingly, a blocking anti-PD-1 antibody improved the anti-tumor effect of 3p-GPC-3 siRNA, predominantly by activating the immune response, reversing immune exhaustion, and improving immune memory. Our study suggests that the combination of 3p-GPC-3 siRNA administration and PD-1 blockade may represent a promising therapeutic strategy for HCC.

Activation of the stimulator of interferon gene (STING)-mediated innate immune response has been suggested as a promising therapeutic strategy for cancers. However, the effects of STING agonist on natural killer (NK) cell-mediated anti-tumor responses in pancreatic cancer remains unknown. Herein, we evaluated the effects of a classical STING agonist cyclic GMP-AMP (cGAMP) on NK cells in pancreatic cancer. We found that cGAMP could directly activate NK cells and enhance the sensitivity of pancreatic cancer cells to NK cell cytotoxicity, suggesting that cGAMP may become a potential adjuvant for NK cell therapy. In addition, combination of CAR-NK-92 cells targeting mesothelin and cGAMP displayed greater antitumor efficacy by inhibiting tumor growth and prolonging survival of the mouse model of pancreatic cancer. These results suggest that the combination of a STING agonist and NK cells may become a novel immunotherapy strategy for pancreatic cancer.

Eurasian drylands are the regions that are most vulnerable to climate change. Climate extremes have caused enormous or even devastating impacts on ecosystems and the social economy in this region, and the compound climate extremes (com_CEs, two or more extreme events occurring simultaneously) and cascading climate extremes (cas_CEs, two or more extreme events occurring successively) have exacerbated these problems. However, little is known about the occurrence patterns of com_CEs and cas_CEs in the Eurasian drylands. Based on the ERA5 reanalysis data range from 1979 to 2020, we improved the methodology for the extraction of co-occurrence events and identified high-frequency types, their hotspots, and occurrence rhythms (seasonally and annually) in Eurasian drylands. Our results showed that com_CEs and cas_CEs have high similarities in the types and spatial hotspots of extreme events; however, the former has a wider geographical and spatial distribution, and the latter has a longer duration. Specifically, co-occurring drought and heatwave events (DH) frequently appear in South Asia and western mid-latitude regions during summer, while in the winter, high latitude regions should be alert to the co-occurrence of drought and low-temperature events (DT). Central Asia and the Mongolian Plateau regions are prone to frequent drought and wind events (DW), and wind and high precipitation events (WP) in the spring and autumn. We have noticed that mid-latitude may suffer from extreme events that have never occurred before, such as com_DH being scattered sporadically in the first two decades and suddenly surging in West Asia and East Asia after the year 2000, and com_DT migrating from high-latitude areas such as the Arctic Ocean coast to mid-latitudes. Our results contribute to understanding hotspots of co-occurring CEs in Eurasian drylands, where more efforts will be needed in the future, especially in mid-latitudes which may suffer extreme climate events that have never occurred before.

To test the effect of pre-curing time on the impact resistance of reactive powder concrete (RPC), RPC specimens were cured in a steam curing box at a temperature of 70 °C for 72 h with pre-curing times of 18, 24, and 30 h. At 28 days, the low-speed impact test was carried out on RPC specimens with a Ceast9350 drop weight impact system at an impact rate of 5 m/s and impact energy of 140 J. The variation curves of the impact force and displacement of RPC specimens with impact times were obtained. The results show that the impact resistance of RPC specimens improved with the increased pre-curing time, implying that appropriate pre-curing time (30 h in this case) can improve RPC mechanical properties. At the same time, combined with x-ray diffraction, scanning electron microscope imaging of hydration products, and the energy dispersion spectroscopy test, the influence mechanism of pre-curing time on the impact resistance of RPC is analyzed from the microstructure standpoint. The results show that appropriate pre-curing time can make the hydration of cement form finer particles and make the hardened paste form a protective structure to reduce the damage of steam curing in the strength development process. Through multiscale homogenization calculation via the Mori–Tanaka scheme, it can be seen that RPC’s stiffness increases with the prolonged pre-curing time. Optimizing pre-curing time is conducive to improving the mechanical properties of RPC specimens.

Abstract In the context of cancer therapy, a recently identified therapeutic target is represented by the essential subtype of RNA transcripts ‐ the long noncoding RNAs (lncRNA). While this is the case, it is especially difficult to successfully regulate the expression of this subtype in vivo, particularly due to the protection granted by the nuclear envelope of nuclear lncRNAs. This study documents the development of a nucleus‐specific RNA interference (RNAi) nanoparticle (NP) platform for the targeted regulation of the nuclear lncRNA function, in order to effectuate successful cancer therapy. An NTPA (nucleus‐targeting peptide amphiphile) and an endosomal pH‐responsive polymer make up the novel RNAi nanoplatform in development, which is capable of complexing siRNA. The nanoplatform is capable of accumulating greatly in the tumor tissues and being internalized by tumor cells, following intravenous administration. The exposed complexes of the NTPA/siRNA may conveniently escape from the endosome with the pH‐triggered NP disassociation, following which it can target the nucleus by specifically interacting with the importin α/β heterodimer. In orthotopic and subcutaneous xenograft tumor models, this would result in a notable suppression of the expression of nuclear lncNEAT2 as well as greatly impede the growth of tumors in liver cancer.

The group of receptor-interacting protein (RIP) kinases has seven members (RIPK1–7), with one homologous kinase domain but distinct non-kinase regions. Although RIPK1–3 have emerged as key modulators of inflammation and cell death, few studies have connected RIPK4–7 to immune responses. The divergence in domain structures and paralogue information in the Ensembl database have raised question about the phylogeny of RIPK1–7. In this study, phylogenetic trees of RIPK1–7 and paralogues constructed using full-length amino acid sequences or Kinase domain demonstrate that RIPK6 and RIPK7 are distinct from RIPK1–5 and paralogues shown in the Ensembl database are inaccurate. Comparative and evolutionary analyses were subsequently performed to gain new clues about the potential functions of RIPK3–7. RIPK3 gene loss in birds and animals that undergo torpor, a common physiological phenomenon in cold environments, implies that RIPK3 may be involved in ischemia-reperfusion injury and/or high metabolic rate. The negligible expression of RIPK4 and RIPK5 in immune cells is likely responsible for the lack of studies on the direct role of these members in immunity; RIPK6 and RIPK7 are conserved among plants, invertebrates and vertebrates, and dominantly expressed in innate immune cells, indicating their roles in innate immunity. Overall, our results provide insights into the multifaceted and conserved biochemical functions of RIP kinases.

Objectives The present study aimed to determine the bidirectional relationship between cognitive function and the loss hierarchy of activities of daily living (ADL) among older adults in China.Design Data were derived from the Longitudinal Study on Family Caregivers for Frail Older Adults Aged 75 or Above in Shanghai (2010–2013).Setting Community-dwelling older adults and their primary caregivers were invited to participate in this research.Participants The inclusion criteria for the older adults were as follows: (a) have a Shanghai urban household registration status, (b) be 75 years old or older, (c) have no fewer than two limitations in ADLs or equivalent, and (d) have one primary caregiver aged 18 years or older. 469 older adults cared by their spouses or children were included in the final analytical sample of this research.Primary and secondary outcome measures Cognitive function was assessed using the Chinese version of the Short Portable Mental Status Questionnaire and ADLs were measured by self-reports of having difficulty or needing help with basic daily activities.Results Cognitive function in 2010 was a significant predictor of intermediate loss of ADLs in 2013 (β=−0.13, p