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Abstract Objective Employing whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short‐term responses to first‐line treatment. Methods We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. Results A total of 577 patients were included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non‐spasms at the initial seizure onset. A total of 532 patients completed the first‐line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early‐onset seizures (≤3 months) than the no‐response group (11.3% vs. 23.7%, p

Abstract Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

BackgroundHigher rates of physical inactivity and comorbid conditions are reported in Hispanic/Latinx and Black cancer patients receiving chemotherapy compared to their White counterparts. Despite the beneficial effect of exercise training for cancer patients, rates of participation in exercise oncology clinical trials are low among disadvantaged and racial and ethnic minority groups. Here, we will examine the effect of an exercise intervention using a novel, accessible, and cost-effective home-based exercise approach among Hispanic/Latinx and Black cancer patients receiving chemotherapy on exercise participation and cardiovascular disease risk.MethodsThe THRIVE trial is an 8-month prospective, three-arm study of 45 patients who are randomized in a 1:1:1 fashion to a supervised exercise intervention (SUP), unsupervised exercise (UNSUP), or an attention control (AC) group. Eligible patients include those with breast, colorectal, or prostate cancer, who are sedentary, overweight or obese, self-identify as Hispanic/Latinx or Black, and plan to receive chemotherapy. Patients randomized to the SUP group participate in a home-based 16-week periodized aerobic and resistance exercise program performed three days per week, supervised through video conference technology. Patients randomized to the UNSUP group participate in an unsupervised 16-week, telehealth-based, periodized aerobic and resistance exercise program performed three days per week using the same exercise prescription parameters as the SUP group. Patients randomized to the AC group receive a 16-week home-based stretching program. The primary outcome is changes in minutes of physical activity assessed by 7-day accelerometry at post-intervention. Secondary outcomes include cardiovascular risk factors, patient-reported outcomes, and physical function. Outcome measures are tested at baseline, post-intervention at month 4, and after a non-intervention follow-up period at month 8.DiscussionThe THRIVE trial is the first study to employ a novel and potentially achievable exercise intervention for a minority population receiving chemotherapy. In addition, this study utilizes an intervention approach to investigate the biological and behavioral mechanisms underlying exercise participation in these cancer patients. Results will guide and inform large randomized controlled trials to test the effect of home-based exercise on treatment outcomes and comorbid disease risk in minority patients with cancer undergoing chemotherapy.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05327452, identifier (NCT#05327452).

Abstract There is increasing evidence that miRNAs play an important role in the prognosis of HCC. There is currently a lack of acknowledged models that accurately predict patient prognosis. The aim of this study is to create a miRNA-based model to precisely forecast a patient’s prognosis and a miRNA–mRNA network to investigate the function of a targeted mRNA. TCGA miRNA dataset and survival data of HCC patients were downloaded for differential analysis. The outcomes of variance analysis were subjected to univariate and multivariate Cox regression analyses and LASSO analysis. We constructed and visualized prognosis-related models and subsequently used violin plots to probe the function of miRNAs in tumor cells. We predicted the target mRNAs added those to the String database, built PPI protein interaction networks, and screened those mRNA using Cytoscape. The hub mRNA was subjected to GO and KEGG analysis to determine its biological role. Six of them were associated with prognosis: hsa-miR-139-3p, hsa-miR-139-5p, hsa-miR-101-3p, hsa-miR-30d-5p, hsa-miR-5003-3p, and hsa-miR-6844. The prognostic model was highly predictive and consistently performs, with the C index exceeding 0.7 after 1, 3, and 5 years. The model estimated significant differences in the Kaplan–Meier plotter and the model could predict patient prognosis independently of clinical indicators. A relatively stable miRNA prognostic model for HCC patients was constructed, and the model was highly accurate in predicting patients with good stability over 5 years. The miRNA–mRNA network was constructed to explore the function of mRNA.

This paper is devoted to studying the existence of positive solutions of the problem: \begin{equation} \begin{cases}\label{0.1}\tag{$\ast$} -\Delta u=\frac{u^{p}}{|x|^{a}}+h(x,u,\nabla u), & \mbox{in} \ \Omega,\\ u=0, & \mbox{on}\ \partial\Omega,\\ \end{cases} \end{equation} where $\Omega\subset \mathbb{R}^{N}(N\geq3)$ is an open bounded smooth domain with boundary $\partial\Omega$, and $1

ABSTRACTDental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.

ObjectiveTo the literature, variants in the ATP6AP2 gene may cause abnormal nervous system development and associated neurological symptoms.MethodsWe report a patient with developmental and epileptic encephalopathy (DEE) carrying an ATP6AP2 c.858G > A (p.Ala286=) synonymous variant. In addition, an overview of reported patients with the same variant were collected and summarized to compare our findings.ResultsThe patient started experiencing tonic seizures at 3.5 months of age, and magnetic resonance imaging (MRI) indicated impaired brain white matter development and reduced left hippocampal volume. Furthermore, electroencephalography showed multifocal interictal epileptiform discharges. Treatment with various anti-seizure medications yielded unsatisfactory results, and the disorder eventually developed into epileptic spasms. An in vitro splicing assay for the ATP6AP2 gene mRNA revealed that the variant caused a deletion in exon 8 and a corresponding protein truncation. A review of previously reported ATP6AP2-related DEE patients found that synonymous variants in the ATP6AP2 gene can cause early DEE onset, progressive changes in early-life MRI, and exon skipping in all ATP6AP2-related DEE patients.SignificanceWe found that synonymous variants in ATP6AP2 may have significant pathogenicity and are highly correlated with DEE. Due to increased isoform production, ATP6AP2 synonymous variants may cause nervous system developmental disorders by competitively reducing the generation of full-length transcripts, resulting in defects in ATP6AP2-related physiological processes.

BackgroundOverwhelming evidence points to that genetic factors contributing to the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights.MethodsGenomic DNA was extracted from both patients’ and controls’ peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology.ResultsA case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/TNIP1 was associated with LOAD (p = 0.035), and rs5011436/TMEM106B was associated with AD in males (p = 0.044) in the genotype model. In the allele model, rs871269/TNIP1 was found to be associated with PD in the Chinese Han population (p = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/GRN was identified as a risk factor for Parkinson’s disease dementia (PDD) in the Chinese Han population (p = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/AGRN, rs6891966/HAVCR2, rs2452170/NTN5, rs1761461/LILRB2) in terms of allele or genotype frequencies.ConclusionThis study identifies rs871269/TNIP1 as a potential risk factor for both LOAD and PD, rs708382/GRN as a risk factor for PDD, and rs5011436/TMEM106B as associated with AD in males when stratified by age.

Abstract Objective Biallelic variants of RARS1, a gene that encodes the cytoplasmic tRNA synthetase for arginine (ArgRS), are associated with central nervous system (CNS) manifestations, such as hypomyelinating leukodystrophy‐9 and developmental and epileptic encephalopathy (DEE). This study aimed to better understand the RARS1 biallelic mutations and the associated phenotypes, particularly in patients with DEE. Methods We identified two patients with RARS1 biallelic mutations and functionally validated these mutations in vitro. Furthermore, we performed a review of the literature. Results Two patients with hypomyelinating leukodystrophy were found to have RARS1 biallelic variants (Patient 1: c.1535G>A (p.Arg512Gln) and c.1382G>A (p.Arg461His); Patient 2: homozygous variants c.5A>T (p.Asp2Val)). Patient 2 had a severe clinical manifestation of DEE. A review of the literature identified 27 patients from five studies. Among the 29 patients, intellectual disability, developmental delay, and hypomyelination were the common symptoms, while 13 of them exhibited DEE and malformations of cortical development. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 10 patients. ArgRS protein expression and stability were substantially reduced in the two newly identified patients. Significance Patients with RARS1 biallelic mutations frequently exhibit DEE, a severe phenotype, along with hypomyelinating leukodystrophy. Besides its effects on the white matter, this mutation also influences cortical development. Moreover, the variants c.5A>T (p.Asp2Val), c.1382G>A (p.Arg461His), and c.1535G>A (p.Arg512Gln) are pathogenic and affect the expression of ArgRS by reducing the protein stability.

Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.

Abstract A solar chimney power plant (SCPP) is suitable to be deployed in desert areas, but there are few studies on the impact of desert wind and sand. In this paper, numerical simulations for the Spanish prototype SCPP were conducted to investigate desert environmental parameters, including sand movement, crosswind, and sand deposition, on the output performance of SCPP. The results indicate that the main erosion area of the turbine blade in the SCPP is the leading edge of the blade pressure surface. The erosion area of the suction surface is much less than that of the pressure surface, mainly concentrated on the leading edge. The output power of SCPP is reduced by 73.3% because of the crosswind and it decreases by 16.9% after the windbreak wall is installed. The sand and dust deposition would affect the transmissivity of the solar radiation through the collector cover. In a dusty environment for 1 month, the system output power decreased by 12.9%, and the collector efficiency decreased from 34% to 23% due to the sand deposition. These results show that the sand has a considerable negative effect on the performance of SCPP in ways of sand erosion and deposition. Sand removal is necessary for SCPP.

Forage supply has been stressed due to the rapid increase in China's livestock consumption. However, the long-term dynamics of the relationships between forage demand and multi-sourced supply are not understood. Here, we examine the annual forage demand, or practical carrying capacity (PCC), and supply, or theoretical carrying capacity (TCC) from 2000 to 2019 in China. We construct a forage supply-demand index (FSDI) to represent the forage supply pressure using MODIS-derived net primary productivity products and provincial statistical datasets, and we consider two scenarios. First, natural grasslands are the sole source of forage. Second, natural grassland forage supply is supplemented with straw crops. We find an increase in PCC in northwestern China's major pastoral and agropastoral provincial regions, including Inner Mongolia, Gansu, Ningxia and Qinghai, at rate of 0.24-3.59 million sheep units (SU) a year. As the primary source of forage, the theoretical carrying capacity of natural grasslands (TCCgrass) expanded at a rate of 3 million SU/yr nationally. Crop straws fed 126.58 million SU nationally in 2019, which accounted for 11.3% of the total practical carrying capacity and alleviated the forage supply pressure by reducing FSDI by 26.56%. During 2000–2019, the theoretical carrying capacity of straw crops (TCCcrop) increased rapidly from 76.5 million SU to 126.6 million SU, which accounted for 10%-15% of the total forage supply at the national scale. We also discovered large carrying capacity gaps (TCCgap) in the northwestern pastoral provincial regions of Inner Mongolia, Xinjiang, Gansu, and some agricultural provinces such as Shandong and Henan, when we considered forage supply from both natural grasslands and straw crops. Our findings showed a large forage gap in the traditional pastoral regions, and we also discussed green fodder as a potential solution for balancing the supply of and demand for forage, which may shed light on crop and forage planning.

Abstract Introduction This study aimed to understand the impact of the coronavirus disease 2019 (COVID-19) epidemic on the distribution and antibiotic resistance of pathogenic bacteria isolated from the lower respiratory tract of children in our hospital. Methods Antimicrobial susceptibility tests were performed on bacteria isolated clinically from the lower respiratory tracts of children in our hospital from 2018 to 2021 by the Kirby–Bauer method and automated systems. Results From 2018 to 2021, the top three lower respiratory tract clinical isolates in our hospital were Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. These three species showed obvious seasonal epidemic patterns, and their numbers decreased significantly during the COVID-19 epidemic, from 4559 in 2019 to 1938 in 2020. Bacterial resistance to antibiotics also changed before and after the COVID-19 epidemic. The annual proportions of methicillin-resistant S. aureus (MRSA) were 41%, 37.4%, 26.2%, and 29.8%. The resistance rates of Klebsiella pneumoniae to ceftriaxone were 40.5%, 51.9%, 35.3%, and 53.3%, and the detection rates of carbapenem-resistant K. pneumoniae (CRKP) were 2.7%, 11.1%, 5.9%, and 4.4%. The detection rates of β-lactamase-producing H. influenzae were 51.9%, 59.2%, 48.9%, and 55.3%. The rate of MRSA, ceftriaxone-resistant K. pneumoniae, CRKP, and β-lactamase-producing H. influenzae decreased significantly in 2020 compared with 2019, whereas that of carbapenem-resistant P. aeruginosa and carbapenem-resistant A. baumannii increased. The detection rates of β-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) gradually increased over the 4 years. Conclusions Protective measures against COVID-19, including reduced movement of people, hand hygiene, and surgical masks, may block the transmission of S. pneumoniae, H. influenzae, and M. catarrhalis and reduce the detection rate of MRSA, ceftriaxone-resistant K. pneumoniae, CRKP, and β-lactamase-producing H. influenzae.

Urban green space (UGS) is increasingly recognized as a nature-based solution to achieving urban sustainable development. Under rapid urbanization, greening policies are often the main driving factor behind the restoration or even growth of UGS. In this study, Chengdu, the pioneering “park city” in China, is chosen as a representative region. Based on land use/land cover (LULC) and normalized difference vegetation index (NDVI) data, indicators that can reflect both UGS quantity and quality are constructed and the spatio-temporal characteristics of UGS in original and expanding urban areas are also explored at different greening policy stages. The findings show that, from 2000 to 2022, the basic trend of UGS reduction during urbanization remained unchanged, despite the greening policies implemented in Chengdu. However, the original urban area has evolved into a new urban area. This has been achieved by integrating the expanded urban area with higher greening rates, resulting in the greening rate in 2022 (44.61%) being restored to the 2000 level (44.21%). The implementation of green policies in Chengdu is primarily reflected in improved UGS quality, especially in the stage of the ecological garden city construction (2008–2018). Specifically, the UGS quality in the original urban area has been improved by 25.25%. Overall, the UGS quality in Chengdu Urban Center has improved, changing from a medium level in 2000 to a medium-high level in 2022. The construction of a national demonstration zone of the park city provides an opportunity for the UGS quantity to increase and quality to improve in Chengdu in the future. However, effectively considering the development positioning of the Tianfu Granary to coordinate the relationship between UGS and high-quality farmland is a huge challenge for urban sustainable development in Chengdu.

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

BackgroundFecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.MethodsThis systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.ResultsThe search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.ConclusionCompared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.

An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a strategy that identification of small-molecular compounds to block the entry is of great significance for COVID-19 prevention. Our study evaluated the potential efficacy of natural compound oxalic acid (OA) as an inhibitory agent against SARS-CoV-2 invasion, particular on the interaction of the receptor binding domain (RBD) of Delta and Omicron variants to ACE2. By employing a competitive binding assay in vitro, OA significantly blocked the binding of RBDs from Delta B.1.617.2 and Omicron B.1.1.529 to ACE2, but has no effect on the wide-type SARS-CoV-2 strain. Furthermore, OA inhibited the entries of Delta and Omicron pseudovirus into ACE2 high expressing-HEK293T cells. By surface plasmon resonance (SPR) assay, the direct bindings of OA to RBD and ACE2 were analyzed and OA had both affinities with RBDs of B.1.617.2 and B.1.1.529 and with ACE2. Molecular docking predicted the binding sites on the RBD-ACE2 complex and it showed similar binding abilities to both complex of variant Delta or Omicron RBD and ACE2. In conclusion, we provided a promising novel small-molecule compound OA as an antiviral candidate by blocking the cellular entries of SARS-CoV-2 variants.

The growing population, the transition dietary towards animal-based products, and the preference for the brand of grass-feeding livestock are bringing increasing pressure on natural grasslands, especially for dry-land areas. The Xilingol League of China is famous for its free-range livestock product, however, overgrazing and herders’ benefits damage are always serious issues for this semi-arid grassland region. This study focuses on the relationship between the supply of natural grassland and the consumption of free-range livestock in the Xilingol League, and this study employed the grassland carrying capacity as the index to judge the sustainability states and its trends of the local grass-feeding system. Satellite data production of net primary production was used for grassland production, statistical livestock data and the consumption model were used for actual forage consumption, and empirical key informant interview data were used to obtain a more comprehensive understanding. The results show that: (1) the natural grassland carrying capacity of the Xilingol League fluctuated, showing improvement from 2000 to 2021; (2) the grassland management needs to be more diversified in different regions with different natural conditions; and (3) while the demand for free-range, high-quality beef is increasing, attention should be paid to the carrying capacity of natural pastures and more consideration should be taken of the benefits of balancing the livelihood of herders, policy strategies, and the customers’ preferences. Potential ways of doing this include employing technologies to improve livestock production, and further exploring and promoting the economic value of the free-range livestock and the geographical indication to get the economic–ecological win-win situation. The research framework and results would be beneficial to reveal the potential threats in pastoral areas and provide support for the optimization of the regional grass-feeding breeding system, especially in middle-income countries.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disease that affects patients with known genetic defects and is increasingly found among those with autoimmune diseases and persistent infections. Talaromyces marneffei (TM) is a human opportunistic fungus that commonly infects immunodeficient or immunosuppressed individuals. Few TM-associated secondary HLH cases resulting from autoimmune deficiency have been reported previously. The current case study describes a pediatric patient hospitalized with recurrent fever and lymphadenopathy. The child had abnormal blood cell classification, and microscopy revealed mature granulocytes that phagocytized fungal spores. It was speculated that the patient was infected with TM. The pathogen was detected earlier than the blood culture and confirmed by metagenomic next-generation sequencing. Whole-exome sequencing revealed that the patient had complex mutations associated with immunodeficiency. This included a mutation in exon 3 of the CD40LG gene, c.346G>A, which may be linked to hyper-IgM syndrome, a primary immunodeficiency disease with immunoglobulin conversion recombination defects that could explain the patient’s increased susceptibility to serious opportunistic infections. In addition, a heterozygous frameshift variant, c.820dup (p.Asp274GlyfsTer61), was detected in exon 6 of CARD9, a key gene associated with fungal immune surveillance. After 4 days of fungal treatment, the abnormal blood cell clusters disappeared, but other infections occurred in succession for 6 months after rehabilitation. The patient was followed with the aim of providing subsequent immunotherapy. This study found that infection can trigger HLH in HIV-negative individuals, highlighting the importance of early definitive identification of the causative agent and investigation of potential immunodeficiency.

Grasslands provide important livestock products such as beef and milk, the main source of daily nutrients for human beings. However, ecological degradation has occurred in nearly 50% of global grasslands, which seriously restricts livestock product supply and impairs human well-beings. Sustainable management measures are explored both in developed and developing regions to curb grassland degradation trend and achieve economic-ecological coordination. We focused on the differences of grassland management measures and their economic-ecological effects between developed regions (US, New Zealand and Western Europe) and developing regions (Inner Mongolia, China) along the “global gold pastures” in middle-latitude zone, by analyzing human-induced grassland productivity changes based on satellite remote sensing, and livestock carrying pressure based on forage-livestock relationship. The results showed the human-induced GPP on grasslands were higher in those developed regions than Inner Mongolia, while the livestock carrying pressures of grasslands were lower, which indicated that the ecological effect of grassland management measures was more positive in the developed regions. Although strict grassland-livestock balance policies had effectively altered the degradation trends in Inner Mongolia grassland, the economic growth still strongly relies on increasing livestock quantity within the grazing limitation, while those developed regions increased the economic benefits and also reduce the ecological pressure caused by livestock grazing in the meantime. Artificial pastures construction together with improved production efficiency effectively mitigated the ecological pressure on grasslands and also brought more economic benefits in those developed regions, which could also enlighten other developing regions to promoting sustainable utilization of grasslands and development of animal husbandry.

The isoleucine–glutamine (IQ) motif and Sec7 domain-containing protein 2 (IQSEC2) gene, located at Xp11. 2, are associated with nervous system diseases, such as epilepsy, autism, and intellectual disabilities. Gender-related differences in the severity of phenotype severity have been described previously. Here, we report the details of seven male children with IQSEC2 mutations from different families. During this investigation, we explored the relationship between the genotype and phenotype of IQSEC2 mutations; to do so, we recruited seven children with pathogenic/likely pathogenic IQSEC2 mutations who were diagnosed with global developmental delay and/or epilepsy. Their clinical features were assessed, and Trio-based whole-exome sequencing (trio WES) was conducted in seven pedigrees. A variety of algorithms and computational tools were used to calculate the pathogenicity, protein stability, conservation, side chain properties, and protein-protein interactions of mutated proteins. The seven patients ranged in age from 18 months to 5 years. Among them, six children were found to have both developmental delay and epilepsy, and one child only exhibited developmental delay. Four novel mutations (c.316C > T, c.443_4 44dup, c.3235T > C, and c.1417G > T) were newly reported. Two patients did not have truncated aberrant proteins caused by missense mutations. Still, they did have severe phenotypes, such as early-onset epilepsy in infancy, because the mutations were located in domains like the pleckstrin homology and IQ calmodulin-binding motif domains. The bioinformatics analysis also proved that missense mutations may be located in the functional region, which affects protein stability and is harmful. In summary, severe phenotypes, such as early-onset epilepsy in infancy, occur in male patients with a missense mutation in specific domains (e.g., pleckstrin homology and IQ calmodulin-binding motif domains). Some female individuals with IQSEC2 mutations may be asymptomatic because of the skewed inactivation of the X chromosome.

Abstract HBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF–MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P

Suaeda salsa, as the last biological barrier of coastal wetlands from land to sea, is one of the best nature-based restoration solution for shoreline stabilization and soil improvement in coastal wetlands. The quality of habitat determines the potential scope of wetland ecological restoration. To enlarge the Suaeda salsa area and to prevent the erosion and degradation of coastal wetland shorelines, we assessed the suitability of habitats for Suaeda salsa growth and identified the causes of encroachment into areas suitable for Suaeda salsa growth. Assessing the habitat suitability of the community and its disturbance status can not only effectively determine the suitable areas for Suaeda salsa ecological restoration, but also can propose targeted solutions according to the interference factors. Moreover, this way can greatly improve the survival rate and coverage area of Suaeda salsa restoration, reduce unnecessary input and loss, enhance the ability to resist coastal wetland shoreline erosion and degradation, and maintain the stability and integrity of the coastal wetland ecosystem. In this study, based on the data of 180 sampling points in the Liaohe estuary wetland, habitat suitability was identified, and the MaxEnt model (habitat suitability model) was used to analyze the suitable distribution area. The interannual changes in Suaeda salsa and reclamation activities in the Liaohe estuary wetland during the past 30 years were extracted from Landsat remote sensing images, and the temporal and spatial dynamic relationship between the distribution of Suaeda salsa and reclamation was analyzed. The dominant factors affecting the distribution of Suaeda salsa were water salinity as well as soil Cd and Zn levels, with influence weights of 49.1%, 28.9%, and 18.0%, respectively, and a total weight of 96%. Compared with the existing 596 hm2 of Suaeda salsa vegetation in the Liaohe estuary wetland, the area highly suitable for growth was 12,306 hm2, whereas the area with medium suitability was 12,100 hm2. Reclamation and aquaculture areas accounted for 33.31% of the highly suitable area and were the main reasons for habitat fragmentation. The study explained the reasons for the difficulty of ecological restoration of Suaeda salsa due to unsuitable habitat quality, and revealed a strong conflict between coastal reclamation and environmental protection, suggesting that the protection of coastal wetlands should consider changes in industrial model strategy. The restoration, reconstruction, and sustainable management of Suaeda salsa communities can be achieved by reducing the proportion of reclamation areas. This study improves the ecological restoration theory of degraded wetlands and provides a theoretical basis for coastal wetland protection and nature-based restoration programs.

Abstract Predicting the change in carbon storage in regions of high carbon uptake and those under highly intensive human disturbance is crucial for regional ecosystem management to promote sustainable development of the economy and ecology in the future. We use a process‐based model to estimate the terrestrial carbon storage in Yangtze River Economic Belt (YREB) and to predict the change of carbon storage over the next 100 years. The results show that the vegetation carbon (VC) and soil organic carbon (SOC) storage were 8.97 and 28.85 Pg C in the YREB from 1981 to 2005, respectively. The highest VC density is distributed in the southern region of the YREB, and the highest SOC density distributes in subalpine and alpine area of the western region of the YREB. Carbon storage in the YREB continued to increase from 1981 to 2005 and in future projections, under both the representative concentration pathway 4.5 (RCP4.5) and the RCP8.5 scenarios. The increased rate of carbon storage in the YREB under the RCP8.5 scenario is higher than that under the RCP4.5 scenario. Under the RCP4.5 scenario, the increasing trend of VC storage tends to be reduced after the 2060s; conversely, the increase of both VC and SOC is accelerated after the 2050s under the RCP8.5 scenario. The SOC density in Western Sichuan will decrease in the future, especially under the RCP8.5 scenario. Western Sichuan has the highest SOC density in the YREB; therefore, it is important to manage the ecosystems there in order to cope with significant warming. The positive impact of warming and the CO2 fertilization effect on vegetation growth and carbon uptake will be predominantly attributed to the increase of terrestrial carbon storage in the YREB. However, warming will stimulate the decomposition of soil organic carbon, contributing directly to reducing SOC storage in high‐altitude regions (e.g., alpine and subalpine regions of Western Sichuan).

Abstract B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11c high CD95 high ) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10–20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury.

Root growth and development is an important indicator of root-zone hypoxia tolerance in rice. Melatonin has been suggested to function as a crucial regulator in modulating root growth and improving plant abiotic stress resistance. To explore the role and potential mechanism of melatonin in regulating the root growth under root-zone hypoxia stress, rice seedlings were treated with hypoxia (oxygen level at 0.9–2.1 mg·L−1), combined with or without a 20 μmol·L−1 melatonin pretreatment under a hydroponic condition. The results showed that the exogenous application of melatonin significantly alleviated the inhibition of the rice root growth that was induced by the hypoxia stress. The morphological–phenotypic analyses showed that after the melatonin pretreatment, the primary root length, lateral root length, and lateral root density increased by 11.6%, 8.2%, and 36.8%, respectively, under hypoxia stress. The physiological–biochemical analyses showed that the exogenous melatonin significantly increased the root activity and O2 influx in the root meristem zone under hypoxia stress to 1.5 times that observed in the hypoxia stress group. The melatonin pretreatment significantly improved the activity of superoxide dismutase (SOD) and decreased the accumulation of superoxide anions (O2•−) in the seedling roots, whereas it increased the content of hydrogen peroxide (H2O2) under hypoxia stress. The exogenous melatonin pretreatment significantly increased the content of indole-3-acetic acid (IAA) by 51.5% in the rice roots compared to the plants without melatonin pretreatment under hypoxia stress. Quantitative real-time PCR (qRT-PCR) analyses revealed that the melatonin pretreatment induced the expression of OsPIN1a~1d, OsPIN8, OsPIN9, OsAUX1, OsARF19, and OsGH3-2 in the rice seedling roots under aerated conditions, whereas it only obviously upregulated the expression of OsPIN1b, OsPIN2, and OsGH3-2 under hypoxia stress. These results indicate that melatonin positively regulates root growth and development under hypoxia stress, through improving the antioxidant system and directly or indirectly activating the auxin signaling pathway. This study demonstrates the important role of melatonin to modulate root growth under hypoxia stress, providing a new strategy for improving hypoxia tolerance.

Chikungunya virus (CHIKV) is an emerging mosquito-transmitted alphavirus that leads to acute fever and chronic debilitating polyarthralgia. To date, the mechanism underlying chronic recurrent arthralgia is unknown. In the present study, newborn wild-type C57BL/6 mice were infected with CHIKV, and the virological and pathological features of CHIKV infection were analyzed over a period of 50 days. Acute viral infection was readily established by footpad inoculation of CHIKV at doses ranging from 10 plaque forming unit (PFU) to 106 PFU, during which inoculation dose-dependent viral RNA and skeletal muscle damage were detected in the foot tissues. However, persistent CHIKV was observed only when the mice were infected with a high dose of 106 PFU of CHIKV, in which low copy numbers (103−104) of viral positive strand RNA were continuously detectable in the feet from 29 to 50 dpi, along with a low level and progressive reduction in virus-specific CD8+ T cell responses. In contrast, viral negative strand RNA was detected at 50 dpi but not at 29 dpi and was accompanied by significant local skeletal muscle damage at 50 dpi when mild synovial hyperplasia appeared in the foot joints, although the damage was briefly repaired at 29 dpi. These results demonstrated that a high viral inoculation dose leads to viral persistence and progression to chronic tissue damage after recovery from acute infection. Taken together, these results provide a useful tool for elucidating the pathogenesis of persistent CHIKV infection and viral relapse-associated chronic arthritis. Author summary CHIKV infection has caused several outbreaks and affected millions of people in epidemic areas since the virus was originally isolated in 1952. CHIKV is transmitted by mosquitoes, resulting in acute diseases typically characterized by severe and debilitating arthritis, myalgia and fever, followed by persistent or recurrent joint and muscle pain that may last for months to years. The persistence of CHIKV in patients has been validated by clinical evidence, but it remains unclear how chronic and recurrent tissue injury are correlated with persistent viral infection. In this study, we established acute and chronic CHIKV infections in mice with different viral inoculation doses and identified the correlation of infection dose with outcomes resulting from CHIKV infection. We found that a high inoculation dose not only resulted in persistent viral infection but also led to a typical acute-recovery-relapse model of myositis and joint injury in mice. We also found that CHIKV RNA replication was interrupted after the acute phase, which might be related to the low antiviral T cell responses and relapse of histopathological injuries. Our study highlights the key factors involved in the clinical outcomes after CHIKV infection and provides new insights into the interaction between viral persistence and recurrent arthritis.

Despite the fact that significant research efforts have been made to the traffic flow theory of autonomous vehicles and manual vehicles, few existing studies have incorporated different modes of both vehicles in their analysis. In this study, we develop a cellular automata simulation model to investigate the impact of different modes of autonomous vehicles (autonomous car, autonomous bus, and autonomous micro car) and conventional vehicles (manual car, manual bus, and manual micro car) on the characteristics of traffic flow. A new type of autonomous mode, i.e., autonomous micro car, is investigated in the model to study the effects of this vehicle mode on the overall capacity of the network. Furthermore, two types of lane-changing behavior, i.e., aggressive lane changing and polite lane changing, are incorporated into the model. The results reveal that micro cars (manual and autonomous) have the potential to reduce traffic congestions and increase the capacity or flow rate (vehicles/hour) of the road. Where the average vehicle occupancy is less than 2, if autonomous micro cars are deployed alongside autonomous cars, the flow rate (vehicles/hour) can be increased significantly. The results highlight the significance of the autonomous micro cars to traffic flow, passenger occupancy, and road capacity.

The phenotype of nitrogen permease regulator-like 2 (NPRL2) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and infantile spasms (IS). The association between phenotype and genotype of NPRL2 variants has not been widely explored. This study aimed to explore the phenotype and genotype spectrum of NPRL2-related epilepsy. Here, we presented two clinical cases with NPRL2-related epilepsy, and discussed the characteristics, diagnosis, and treatment processes in the context of existing literature. Two novel NPRL2 likely pathogenic variants were identified by next-generation sequencing, including one splicing mutation (c.933-1G>A), and one frameshift mutation (c.257delG). The results of literature review showed that there were a total of 20 patients with NPRL2-related epilepsy whose mutations were mostly missense and hereditary. These findings indicate that the possibility of NPRL2 gene mutations in focal epilepsy should be considered for patients with family history, and that patients carrying different NPRL2 variants have different clinical manifestations. Our study expanded the genotype spectrum of NPRL2 and suggested that the type of NPRL2 variants might provide important information for the prognosis evaluation.

To address severe grassland degradation problems, China has been implementing several national restoration programs, which have been reported to mitigate the deterioration of grassland ecosystem function. However, the regional differences in the effectiveness of the programs are not yet known. In this study, gross primary productivity (GPP) was selected as an indicator to analyze grassland degradation dynamics, and the residual trend method was used to assess the driving force of grassland degradation based on GPP. The results showed the GPP of Inner Mongolia grassland significantly increased by 3.94 g C m−2 yr−1 during 2000–2015, climate change was the dominant driving factors, while human activities slightly reduced grassland productivity (−0.17 g C m−2 yr−1). But there are obviously spatial heterogeneous on the impact of human activities. Specifically, grassland management significantly promoted the GPP increase in semidesert steppe, while grazing activity decreased the GPP in meadow and typical steppes. These findings suggest that ecological restoration programs could obviously improve vegetation functioning in ecologically fragile grassland which has relatively very low productivity. However, the grasslands with relative higher productivity or initially non-degraded are still facing with great degradation risk due to the continuous growing livestock scale. Therefore, policy-makers should pay more attention to the originally non-degraded or high productivity grasslands, especially at those years the negative impacts of intensive grazing could be concealed by the well-growth grass under abundant precipitation.

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear.Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated.Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups.Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy.

Land use/cover change (LUCC) research is important for regional ecological conservation and sustainable development. There is a lack of exploration of long-time-series dynamics and driving mechanisms at the national scale in the study of land use/cover change in Thailand. Based on the Global Land Cover product with Fine Classification System in 30m (GLC_FCS30) dataset and socioeconomic statistics, we studied the temporal and spatial evolution characteristics and driving mechanisms of LUCC in Thailand from 2000 to 2020 through indicators and methods such as land use dynamic attitude, mapping of a Sankey diagram, principal component analysis, and multiple linear stepwise regression analysis. The results showed that: (1) Thailand has developed in terms of agriculture and forestry. In 2020, the cropland and forest areas accounted for 53.77% and 32.15% of the land area, respectively. (2) From 2000 to 2020, the area of rainfed cropland, irrigated cropland, and forest continued to shrink; the area of impervious surfaces expanded rapidly, and the area of shrubland, other cropland, and wetlands increased. (3) The LUCC process mainly occurred in the two-way conversion between forest and shrubland, rainfed cropland and irrigated farmland, forest and rainfed cropland, and forest and other farmland. The LUC with the largest area transformed into other land types was forest (2.25 × 104 km2), and the LUC with the largest area transformed from other land types transferring into the area was shrubland (1.40 × 104 km2). (4) From 2000 to 2020, the LUCC process in Thailand was mainly influenced by socio-economics and tourism. Gross population, main grain output, industrial value added, passenger income, and urban population were the key factors driving the LUCC in Thailand. Our research can provide the basis and decision support for the future planning and management of land in Thailand.

The enhanced virulence and infectiousness of the Omicron variant of SARS-CoV-2 is having more significant impacts on certain socioeconomic areas, and rapidly suppressing the spread of the epidemic remains a priority for maintaining public health security throughout the world. Thus, we applied multi-agent modeling theory to create a social simulation model of Omicron variant transmission and prevention and control in order to analyze the virus transmission status in complex urban systems and its changing trends under different interventions. By considering the six municipal districts under the jurisdiction of Taiyuan City as examples, we developed state transition rules between five types of resident agents, mobility and contact behavior rules, and rules for patient admission behavior by hospital agents. We then conducted multi-scenario simulation experiments based on single measures of pharmacological and non-pharmacological interventions under non-governmental control as well as multiple interventions in combination to evaluate the effects of different measures on rapidly suppressing the spread of the epidemic. The experimental results demonstrated the utility of the model and the multi-agent modeling method effectively analyzed the transmission trends for the Omicron variant, thereby allowing a comprehensive diagnosis of the future urban epidemic situation and providing an important scientific basis for exploring more accurate normalized prevention and control measures.

The rapid suppression of SARS-CoV-2 transmission remains a priority for maintaining public health security throughout the world, and the agile adjustment of government prevention and control strategies according to the spread of the epidemic is crucial for controlling the spread of the epidemic. Thus, in this study, a multi-agent modeling approach was developed for constructing an assessment model for the rapid suppression of SARS-CoV-2 transmission under government control. Different from previous mathematical models, this model combines computer technology and geographic information system to abstract human beings in different states into micro-agents with self-control and independent decision-making ability; defines the rules of agent behavior and interaction; and describes the mobility, heterogeneity, contact behavior patterns, and dynamic interactive feedback mechanism of space environment. The real geospatial and social environment in Taiyuan was considered as a case study. In the implemented model, the government agent could adjust the response level and prevention and control policies for major public health emergencies in real time according to the development of the epidemic, and different intervention strategies were provided to improve disease control methods in the simulation experiment. The simulation results demonstrate that the proposed model is widely applicable, and it can not only judge the effectiveness of intervention measures in time but also analyze the virus transmission status in complex urban systems and its change trend under different intervention measures, thereby providing scientific guidance to support urban public health safety.

Research on the spatial distribution and dynamic evolution of land use/cover (LUC) is the basis for land management and ecological protection. However, there is currently a lack of long-term analyses of the evolution of LUC at the national scale in Cambodia. Based on the GLC_FCS30 dataset, this paper analyzes the temporal and spatial evolution of LUC in Cambodia from 2000 to 2020, as well as its relationship with the country’s economic and social development and climate change using dynamic degree, flow direction diagram, principal component analysis, and multivariate stepwise regression. The main findings are as follows. (1) Cropland and forest are Cambodia’s most significant land cover types. In 2020, the proportions of cropland and forest accounted for 47.67% and 42.22% of the total land area. Among the cropland area, rainfed cropland accounted for 35.90%, irrigated cropland accounted for 7.26%, and other cropland accounted for 4.51%. (2) From 2000 to 2020, rainfed cropland areas increased significantly (+4.69 × 103 km2, +7.77%), while irrigated cropland areas increased less (+0.37 × 103 km2, 2.91%). The forest area continued to shrink (−7.71 × 103 km2, −9.16%), and the area of impervious surfaces expanded most significantly (+161.16%). (3) In 2000–2020, the integrated dynamic degree of land use presented a spatial differentiation pattern of high in the northeast, low in the middle, and lowest in the plain area. The most critical LUC change processes were the conversion of forest and shrubland to rainfed cropland and the transformation of rainfed cropland to impervious surfaces. (4) The change in LUC in Cambodia has mainly been affected by economic development and human activities, especially regarding the agricultural added value, agricultural raw material export value, urban population, and urbanization rate. This study will help the Cambodian government to strengthen national land management and planning in a targeted manner and may provide a reference for the analysis of land use change processes in similar areas.

Ecological degradation has occurred in global grasslands and has impaired their ecosystem services severely, so ecological conservation of grasslands should be focused more on the effectiveness of management measures. The green-up process decides the year-round forage yield and ecological conditions of grasslands. Adopting rest-grazing during the green-up process can guarantee a successful green-up, thus realizing more economic benefits without grassland degradation. Therefore, studies should pay more attention to whether the green-up process is really covered by the rest-grazing period or not. We analyze the spatiotemporal variations and the stability of the annual green-up date in Xilin Gol Grassland from 2000 to 2018 based on MODIS time series images and compare the green-up date with the rest-grazing period to assess the effectiveness of the rest-grazing policy. The results show that the green-up date of Xilin Gol Grassland had advanced 15 days on average because of the increasing trend of both temperature and precipitation during 2000~2018. The green-up date is mostly 120~130 d in the east, about 10 days earlier than the west (130~140 d) and 20 days earlier than in the central areas (140~150 d), also because of the spatial variations of temperature and precipitation. The coefficient of variation (CV) of the green-up date showed a significant negative correlation with precipitation, so the green-up date is more unstable in the arid areas. The rest-grazing period started more than 45 days earlier than the green-up date and failed to cover it in several years, which occurred more frequently in southern counties. The average green-up date appeared after rest-grazing started in over 98% of areas, and the time gap is 15~45 days in 88% of areas, which not only could not avoid grassland degradation effectively but also increased herdsmen’s life burden. This study aims to accurately grasp the temporal and spatial variations of the green-up date in order to provide references for adjusting a more proper rest-grazing period, thus promoting ecological conservation and sustainable development of animal husbandry.

Land use/land cover change (LUCC) research is of great significance to land conservation and regional sustainable development. At present, there is a lack of research on the long-term timing of the change process and mechanisms of LUCC that accords with the national level in Laos. Based on the Global Land-Cover product with the Fine Classification System at 30 m (GLC_FCS30) data set as well as economic and social statistical data, the authors analyzed the spatiotemporal regularity and driving mechanism of LUCC in Laos from 2000 to 2020 by using dynamic degree, flow direction analysis, principal component analysis, correlation analysis and other methods. The results show that: (1) Laos is rich in natural ecological resources. In 2020, the forest and shrubland areas accounted for 53.3% and 32.4% of the land area, respectively; (2) from 2000 to 2020, the rate of LUCC across the country continued to rise, and the integrated dynamic degree of LUCC was 14.4%. The change in impervious surfaces is the most drastic. The area of evergreen broad-leaved forest, evergreen needle-leaved forest and grassland continued to shrink, while the area of rainfed cropland, irrigated cropland, deciduous broad-leaved forest, shrubland, wetland and the water body continued to expand; (3) the LUCC process mainly occurred between forest, shrubland and cropland. The LUC with the largest transfer out area is evergreen broad-leaved forest (8.91 × 103 km2), and the LUC with the largest transfer into the area is shrubland (8 × 103 km2); (4) in the past 20 years, the LUCC process in Laos has been mainly affected by macro-socioeconomic development, agricultural development, and forestry development. The population is the key factor driving LUCC in Laos. This study can provide decision-making support for the rational planning and utilization of land resources in Laos.

Ebola virus is among the most dangerous viral pathogens, with a case fatality rate of up to 90%. Since 2013, the two largest and most complex Ebola outbreaks in West Africa have revealed the lack of investigation on this notorious virus.

ABSTRACTp-Aminosalicylic acid (PAS) is an important second-line antibiotic for treating multidrug-resistant tuberculosis (MDR-TB). Due to gastrointestinal disturbance and intolerance, its potent and efficacy in the treatment of extensively drug-resistant (XDR)-TB commonly are poor. Thus, it is important to reveal the mechanism of susceptibility and resistance of Mycobacterium tuberculosis (Mtb) to this drug. Herein, we screened and established PAS-resistant (PASr) folC mutated and un-mutated Mtb strains, then utilized a multi-omics (genome, proteome, and metabolome) analysis to better characterize the mechanisms of PAS resistance in Mtb. Interestingly, we found that promotion of SAM-dependent methyltransferases and suppression of PAS uptake via inhibiting some drug transport associated membrane proteins were two key pathways for the folC mutated strain evolving into the PASr Mtb strain. However, the folC un-mutated strain was resistant to PAS via uptake of exogenous methionine, mitigating the role of inhibitors, and promoting DfrA, ThyA and FolC expression. Beyond these findings, we also found PAS resistance in Mtb might be associated with the increasing phenylalanine metabolism pathway. Collectively, our findings uncovered the differences of resistant mechanism between folC mutated and un-mutated Mtb strains resistant to PAS using multi-omics analysis and targeting modulators to these pathways may be effective for treatment of PASr Mtb strains.

Abstract Background Enterovirus A 71 (EV71) is a neurotropic virus that may lead to acute flaccid paralysis, encephalitis, cardiopulmonary failure or even death. No vaccine and defensive drug controlling EV71 is currently available, novel and efficient antiviral drug or vaccine is therefore urgently needed. 3Dpol (RNA-dependent RNA polymerase (RdRp)) has been an important target for anti-EV71 drug development. Methods A panel of monoclonal IgG antibodies (mAbs) against EV71 3Dpol were generated by traditional cell fusion methods. And the antibody affinity and specificity to EV71 3Dpol were evaluated by Enzyme-linked Immunosorbent Assay (ELISA), Indirect Fluorescent Assay (IFA) and Western blotting. Antiviral activities of these antibodies were also determined in vitro and in vivo. Results Two mAbs towards EV71 3Dpol were able to effectively suppress EV71 replication in Vero-1008 cell when intracellarly delivered. And they also dampened the RNA polymerase activity of 3Dpol in vitro. More importantly, these mAbs provided partial protection in EV71-challenged neonatal murine challenge model. Conclusions These results showed that two of mAbs against EV71 3Dpol inhibited EV71 replication and could be utilized as promising therapeutic drug candidate.

Abstract Background Vascular grafts are widely used as a treatment in coronary artery bypass surgery, hemodialysis, peripheral arterial bypass and congenital heart disease. Various types of synthetic and natural materials were experimented to produce tissue engineering vascular grafts. In this study, we investigated in vivo tissue engineering technology in miniature pigs to prepare decellularized autologous extracellular matrix-based grafts that could be used as vascular grafts for small-diameter vascular bypass surgery. Methods Autologous tissue conduits (3.9 mm in diameter) were fabricated by embedding Teflon tubings in the subcutaneous pocket of female miniature pigs (n = 8, body weight 25–30 kg) for 4 weeks. They were then decellularized by CHAPS decellularization solution. Heparin was covalently-linked to decellularized tissue conduits by Sulfo-NHS/EDC. We implanted these decellularized, completely autologous extracellular matrix-based grafts into the carotid arteries of miniature pigs, then sacrificed the pigs at 1 or 2 months after implantation and evaluated the patency rate and explants histologically. Results After 1 month, the patency rate was 100% (5/5) while the inner diameter of the grafts was 3.43 ± 0.05 mm (n = 5). After 2 months, the patency rate was 67% (2/3) while the inner diameter of the grafts was 2.32 ± 0.14 mm (n = 3). Histological staining confirmed successful cell infiltration, and collagen and elastin deposition in 2-month samples. A monolayer of endothelial cells was observed along the inner lumen while smooth muscle cells were dominant in the graft wall. Conclusion A completely autologous acellular conduit with excellent performance in mechanical properties can be remodeled into a neoartery in a minipig model. This proof-of-concept study in the large animal model is very encouraging and indicates that this is a highly feasible idea worthy of further study in non-human primates before clinical translation.

Research on the spatial distribution and dynamic evolution of land use/land cover (LULC) is the basis for land management and ecological protection. However, there is currently a lack of long-term analysis on the evolution of LULC on the national scale in Vietnam. Based on the GLC_FCS30 dataset, this paper analyzed the temporal and spatial evolution of LULC in Vietnam from 2000 to 2020 as well as its driving mechanism using methods such as dynamicity, flow direction diagrams, principal component analysis, and multivariate stepwise regression. The results show that: (1) cropland, forest, and shrubland are Vietnam’s most important land-cover types. In 2020, the above three types of land area accounted for 34.77%, 32.36%, and 26.13% of the total land area, respectively. (2) From 2000 to 2020, the area of cropland and forest areas continued to shrink (−5.64%, −3.96%); the area of shrubland, water bodies, and other land areas expanded (+4.87%, +12.29%, +15.04%); and the area of impervious surfaces expansion was the most significant (+100.40%). (3) The integrated dynamic degree of LULC in Vietnam shows a spatial differentiation of high in the south, followed by the north, and lowest in the center. In the early period (2000–2010), the LULC rate of change in each region was rapid, while it gradually decreased in the later period (2010–2020). The most important LULC changes in Vietnam can be divided into two parts: (a) the mutual conversion of forest, cropland, and shrubland and (b) one-way conversion of cropland to impervious surfaces. (4) LULC changes in Vietnam are mainly affected by economic development and human activities, especially the GDP, population, and urbanization rate. There is no reliable statistical relationship between LULC and climatic factors. The results of this study contribute to the analysis of LULC processes in similar regions, and will also help the Vietnamese government strengthen national land management and planning in a targeted manner.

Open and high-temporal- and spatial-resolution global land use/land cover (LULC) mapping data form the foundation of global change research and cross-scale land management planning. However, the consistency and reliability of the use of multisource LULC datasets in specific regions need to be quantitatively assessed. In this study, we selected the Indochina Peninsula as the research area; considered four datasets: LSV10, GLC_FCS30, ESRI10, and Globeland30; and analyzed them from four dimensions: the similarity of composition type, the degree of category confusion, spatial consistency, and data accuracy. The results show that: (1) the land composition descriptions of the different datasets are consistent. The study area is dominated by forest and cropland, supplemented by grassland, shrubland, and other land types. (2) The correlation coefficient between datasets is between 0.905 and 0.972; the spatial consistency of datasets is good; and the high-consistency area accounts for 77.87% of the total. (3) The overall accuracy of LSV10 is the highest (83.25%), and that of GLC_FCS30 is the lowest (72.27%). The accuracy of cropland, forest, water area, and built-up land is generally high (above 85%); the accuracy of grassland, shrubland, and bare land is low (below 60%). Therefore, researchers must conduct validation for specific regions and specific land types before using the above datasets. Our findings provide a basis for selecting LULC datasets in related research on the Indochina Peninsula and a reference method for assessing the reliability of multisource LULC datasets in other regions.

Under the pressure of limited arable land and increasing demand for food, improving the quality of existing arable land has become a priority to ensure food security. The Chinese government gives great importance to improving cropland productivity by focusing on the construction of high-standard farmland (HSF). The government puts forward the goal of constructing 1.2 billion mu (100 mu ≈ 6.67 hectares) of HSF by 2030. Therefore, how to apply remote sensing to monitor the ability to increase and stabilize yields in HSF project regions has become an essential task for proving the efficiency of HSF construction. Based on HSF project distribution data, Moderate Resolution Imaging Spectroradiometer (MODIS) data and Landsat-8 Operational Land Imager (Landsat8-OLI) data, this study develops a method to monitor cropland productivity improvement by measuring cropland productivity level (CPL), disaster resistance ability (DRA) and homogeneous yield degree (HYD) in the HSF project region. Taking China’s largest grain production province (Henan Province) as a case study area, research shows that a light use efficiency model that includes multiple cropping data can effectively detect changes in cropland productivity before and after HSF construction. Furthermore, integrated Landsat8-OLI and MODIS data can detect changes in DRA and HYD before and after HSF construction with higher temporal and spatial resolution. In 109 HSF project regions concentrated and distributed in contiguous regions in Henan Province, the average cropland productivity increased by 145 kg/mu; among the eight sample project regions, DRA was improved in seven sample project regions; and the HYD in all eight sample project regions was greatly improved (the degree of increase is more than 75%). This evidence from satellites proves that the Chinese HSF project has significantly improved the CPL, DRA and HYD of cropland, while this study also verifies the practicability of the three indices to monitor the efficiency of HSF construction.

Abstract Background Cigarette smoking (CS) triggers an intense and harmful inflammatory response in lungs mediated by alveolar and blood macrophages, monocytes, and neutrophils and is closely associated with prevalence of tuberculosis (TB). The risk of death in patients with long-term cigarette smoking-related pulmonary tuberculosis (LCS-PTB) is approximately 4.5 times higher than those with nonsmoking pulmonary tuberculosis (N-PTB). However, the mechanisms underlying the harmful inflammatory responses in the setting of LCS-PTB have not been well documented. Methods 28 cases LCS-PTB patients, 22 cases N-PTB patients and 20 cases healthy volunteers were enrolled in this study. Monocytes were isolated from peripheral blood mononuclear cells. Differentiated human MDM and U937 cell were prepared with M-CSF and PMA stimulation, respectively. The miR-196b-5p, STAT1, STAT3, STAT4, STAT5A, STAT5B, STAT6, SOCS1 and SOCS3 mRNA expression were detected by qRT-PCR. Western blot was performed according to SOCS1, SOCS3, and pSTAT3 expression. The mycobacterial uptake by MDMs from different groups of patients after Bacillus Calmette–Guérin (BCG) infection and agomir-196b-5p or antagomir-196b-5p transfection were used by flow cytometry analysis. Human IL-6, IL-10 and TNF-α levels on the plasma and cell culture supernatant samples were measured using ELISA. For dual-luciferase reporter assay, the SOCS3 3′-UTR segments, containing the binding elements of miR-196b-5p or its mutant versions were synthesized as sense and antisense linkers. Results In this study, we found that IL-6, TNF-α production, SOCS3 mRNA expression were downregulated, while miR-196b-5p and STAT3 mRNA expression were upregulated in monocytes from LCS-PTB patients as compared to N-PTB patients. Meanwhile, we demonstrated that miR-196b-5p could target SOCS3 and activate STAT3 signaling pathway, which may possibly contribute to attenuation of BCG uptake and decrease in IL-6 and TNF-α production in macrophages. Conclusions Our findings revealed that CS exposure regulates inflammatory responses in monocyte/macrophages from LCS-PTB patients via upregulating miR-196b-5p, and further understanding of the specific role of miR-196b-5p in inflammatory responses mightfacilitate elucidating the pathogenesis of LCS-PTB, thus leading to the development of new therapeutic strategies for PTB patients with long-term cigarette smoking.