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In this study, analytical solutions are developed to assess the hydraulic and structure responses of underwater tunnels by considering the tidal loading in conjunction with water ingress. Two scenarios are considered, that is, the surface water fluctuation (SWF) and groundwater variation (GWV). A single-step scheme is put forward to obtain the exact horizontal displacement developed at the springline with high efficiency. The proposed analytical method is verified by comparing the result from numerical simulations. A detailed parameter analysis is presented to investigate the effect of soil properties on the ground and tunnel behaviors as well as the discrepancies between these two hydraulic loadings. This study reveals that the underwater tunnel tends to act as drainage in the SWF condition whereas blockage for GWV. Much more intensive hydraulic and structure responses are observed under SWF than GWV, but both cases lead to slight tunnel deformations.

Mesenchymal stem cells have shown noticeable potential for unlimited self-renewal. They can differentiate into specific somatic cells, integrate into target tissues via cell-cell contact, paracrine effects, exosomes, and other processes and then regulate the target cells and tissues. Studies have demonstrated that transplantation of MSCs could decrease the expression and concentration of collagen in the liver, thereby reducing liver fibrosis. A growing body of evidence indicates that apoptotic MSCs could inhibit harmful immune responses and reduce inflammatory responses more effectively than viable MSCs. Accumulating evidence suggests that mitochondrial transfer from MSCs is a novel strategy for the regeneration of various damaged cells via the rescue of their respiratory activities. This study is aimed at reviewing the functions of MSCs and the related roles of the programmed cell death of MSCs, including autophagy, apoptosis, pyroptosis, and ferroptosis, as well as the regulatory pathogenic mechanisms of MSCs in liver fibrosis. Research has demonstrated that the miR-200B-3p gene is differentially expressed gene between LF and normal liver samples, and that the miR-200B-3p gene expression is positively correlated with the degree of liver fibrosis, suggesting that MSCs could inhibit liver fibrosis through pyroptosis. It was confirmed that circulating monocytes could deliver MSC-derived immunomodulatory molecules to different sites by phagocytosis of apoptotic MSCs, thereby achieving systemic immunosuppression. Accordingly, it was suggested that characterization of the programmed cell death-mediated immunomodulatory signaling pathways in MSCs should be a focus of research.

We establish sharp-in-time kernel and dispersive estimates for the Schr\"odinger equation on non-compact Riemannian symmetric spaces of any rank. Due to the particular geometry at infinity and the Kunze-Stein phenomenon, these properties are more pronounced in large time and enable us to prove the global-in-time Strichartz inequality for a larger family of admissible couples than in the Euclidean case. Consequently, we obtain the global well-posedness for the corresponding semilinear equation with lower regularity data and some scattering properties for small powers which are known to fail in the Euclidean setting. The crucial kernel estimates are achieved by combining the stationary phase method based on a subtle barycentric decomposition, a subordination formula of the Schr\"odinger group to the wave propagator and an improved Hadamard parametrix., Comment: 19 pages, major revision with more details

Vegetation has been found to improve the hydrological performance of landfill cover. However, existing studies ignore the effects of hydrogen sulfide (H2S), which forms the toxic odour generated from municipal solid wastes. Hydrogen sulfide is a potential signalling molecule in regulating plant-stomata aperture, but how the plant–hydrogen sulfide interaction affects the water–gas transport in soil remains unknown. This aim of this study was to investigate the effects of hydrogen sulfide on Bermuda grass growth and its influence on water–gas transport in unsaturated soils. Soil columns, with and without vegetation, were prepared and fumigated with different hydrogen sulfide concentrations. These columns were subjected to controlled drought and rainfall sequentially. The results showed that grass leaves almost wilted without hydrogen sulfide fumigation due to the Pythium diseases caused by the antecedent waterlogged conditions. In contrast, hydrogen sulfide fumigation promoted grass growth because of the fungicidal effects of hydrogen sulfide. In drought, hydrogen sulfide fumigation caused stomata closure, which resulted in a lower matric suction in the vegetated soil than that without hydrogen sulfide fumigation. Accordingly, hydrogen sulfide concentration reduced because of oxidation by metal oxides in soil. Upon subsequent rainfall, more infiltration but lower matric suction was observed in vegetated soils than was found in the bare case, whereas hydrogen sulfide concentration decreased continuously due to gas dissolution in the pore water. Direct application of laboratory findings herein to field cases should be used with caution, because the applied continuous lighting and low evapotranspiration rate of the soil column tests may not be representative of field conditions.

Background Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion This work provides a meaningful insight for the mechanism of AAΙ renal injury.

A total of 58 (eight known and 50 new) species of the subgenus Stegana (Steganina) from China were surveyed and (re)described: S. (S.) bacilla Chen & Aotsuka, 2004, S. (S.) belokobylskiji Sidorenko, 1997, S. (S.) hirticeps Wang, Gao, & Chen, 2013, S. (S.) izu Sidorenko, 1997, S. (S.) kanmiyai Okada & Sidorenko, 1992, S. (S.) masanoritodai Okada & Sidorenko, 1992, S. (S.) maymyo Sidorenko, 1997, stat. rev., S. (S.) nigripes Zhang & Chen, 2015, S. (S.) alafoliacea Zhang & Chen, sp. nov., S. (S.) baoxing Li & Chen, sp. nov., S. (S.) bibarbata Li & Chen, sp. nov., S. (S.) bimai Cui & Chen, sp. nov., S. (S.) cinereipecta Zhang & Chen, sp. nov., S. (S.) cardua Cui & Chen, sp. nov., S. (S.) cordhirsuta Wang & Chen, sp. nov., S. (S.) cornuta Li & Chen, sp. nov., S. (S.) cucullata Li & Chen, sp. nov., S. (S.) cultella Cui & Chen, sp. nov., S. (S.) curvitabulata Cui & Chen, sp. nov., S. (S.) daiya Cui & Chen, sp. nov., S. (S.) dendrophila Zhang & Chen, sp. nov., S. (S.) flabella Li & Chen, sp. nov., S. (S.) flavipes Li & Chen, sp. nov., S. (S.) formosa Zhang & Chen, sp. nov., S. (S.) fusca Li & Chen, sp. nov., S. (S.) fuscipes Li & Chen, sp. nov., S. (S.) glaucopalpula Cui & Chen, sp. nov., S. (S.) haba Zhang & Chen, sp. nov., S. (S.) hirticlavata Cui & Chen, sp. nov., S. (S.) iaspidea Zhang & Chen, sp. nov., S. (S.) idiasta Cui & Chen, sp. nov., S. (S.) kanda Cui & Chen, sp. nov., S. (S.) labao Li & Chen, sp. nov., S. (S.) lancang Li & Chen, sp. nov., S. (S.) latifoliacea Wang & Chen, sp. nov., S. (S.) liusanjieae Li & Chen, sp. nov., S. (S.) magniflava Cui & Chen, sp. nov., S. (S.) mailangang Li & Chen, sp. nov., S. (S.) marenubila Cui & Chen, sp. nov., S. (S.) menghai Zhang & Chen, sp. nov., S. (S.) menglian Li & Chen, sp. nov., S. (S.) minutiflava Li & Chen, sp. nov., S. (S.) multiprocera Li & Chen, sp. nov., S. (S.) nayun Li & Chen, sp. nov., S. (S.) nigridentata Wang & Chen, sp. nov., S. (S.) nigripalpula Cui & Chen, sp. nov., S. (S.) otphylla Cui & Chen, sp. nov., S. (S.) radiciflava Zhang & Chen, sp. nov., S. (S.) rava Cui & Chen, sp. nov., S. (S.) sciophila Li & Chen, sp. nov., S. (S.) septencolorata Li & Chen, sp. nov., S. (S.) serrata Zhang & Chen, sp. nov., S. (S.) silvestrella Zhang & Chen, sp. nov., S. (S.) simola Cui & Chen, sp. nov., S. (S.) yani Li & Chen, sp. nov., S. (S.) yixiang Zhang & Chen, sp. nov., S. (S.) zaduo Cui & Chen, sp. nov., and S. (S.) zhuoma Cui & Chen, sp. nov. We also provided a complete list of Chinese Steganina species together with their geographical distributions. In addition, the majority of currently available DNA barcode (partial sequence of the mitochondrial cytochrome c oxidase subunit I (COI) gene) sequences of this subgenus (435 sequences of 102 spp.) were employed in a molecular analysis for species delimitation. Taken together, morphology- and molecular-based species delimitation results reached a consensus for an overwhelming majority of these Steganina species (98 of 102 spp.).

Танхимын сургалтаар ойролцоо утгатай үгсэд анализ хийж заах арга нь хятад хэл суралцаж буй гадаад хүмүүс хятад хэлний ойролцоо утгатай үгсийг суралцах явцад хэрхэн нөлөөлдгийг энэхүү өгүүлэлд бодит жишээгээр баримтжуулан судалгаа хийсэн. Туршилтын үр дүнгээс харахад, ойролцоо утгатай үгсийг задлан шинжилгээ хийж заах нь ойролцоо утгатай үгсийн хоорондын ялгааг таньж мэдэхэд ихээхэн тус дөхөмтэй бөгөөд өөрөө нээн илрүүлэх хэлбэрээр заах арга нь уламжлалт хүлээн авах хэлбэрийн заах аргаас илүү үр дүнтэй байсан. Ойролцоо утгатай үгсэд задлан шинжилгээ хийж заах аргын гол ач холбогдол нь ойролцоо утгатай үгсийг ерөнхийд нь суралцах явцыг түргэсгэх бөгөөд мөн ойролцоо утгатай үгсийн ялгааг ойлгоход их үр нөлөөтэй.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this “two-cell” (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

BACKGROUND: Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure (HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization (MR) study to investigate the causal associations between genetically determined vitamin levels and HF. METHODS: Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium (47,309 cases and 930,014 controls) and FinnGen Study (30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis. RESULTS: Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97 (95% confidence interval [CI]: 0.85–1.09, P = 0.41) for vitamin C to 1.05 (95% CI: 0.61–1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94 (95% CI: 0.75–1.19, P = 0.62) for α-tocopherol and 1.11 (95% CI: 0.98–1.26, P = 0.09) for γ-tocopherol. CONCLUSION: Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore, there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.

Sheng-Yu Li,1 Lei Liu,1 Ding-Kun Wang,1 Xiao-Song Ding,1 Wei-Ping Li,1,2 Hong-Wei Li1,2 1Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, Beijing, People’s Republic of ChinaCorrespondence: Wei-Ping Li; Hong-Wei Li, Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86-13810267817 ; +86-13801396679, Email xueer09@163.com; lhw19656@sina.comPurpose: So far, ST-segment elevation myocardial infarction (STEMI) is still the main cause of morbidity and mortality of cardiovascular diseases worldwide. Recent studies showed that pentraxin-3 (PTX3) was related to the early diagnosis and prognosis of coronary heart disease. This study aimed to investigate the dynamical change of PTX3 after primary percutaneous coronary intervention (pPCI) in STEMI patients and its prognostic value.Patients and methods: In this prospective cohort study, a total of 350 patients were enrolled. The plasma level of PTX3 was measured at admission, 24-hour and 5-day after pPCI. The primary endpoint was the incidence of major adverse cardiac cerebral events (MACCEs) during 1-year follow-up.Results: Compared with the admission, PTX3 levels were significantly increased at 24 hours, and decreased at 5 days after pPCI in the whole cohort. PTX3 levels at these three time points were not significantly different between the patients with and without MACCEs. Notably, the change in PTX3 from admission to post-pPCI 24-hour (ΔPTX3) was higher in patients with MACCEs (112.83 vs 17.94 ng/dl, P = 0.001). The ROC curves showed that the cut-off value was 29.22 ng/dl and the area under curves was 0.622 (95% CI: 0.554– 0.690, p = 0.001). Multivariable cox regression models revealed that the high ΔPTX3 group was an independent predictor of MACCEs (adjusted HR = 2.010, 95% CI = 1.280– 3.186, p = 0.003). The higher ΔPTX3 group had significantly higher incidences of revascularization (HR = 2.094, 95% CI: 1.056– 4.150, p = 0.034) and composite MACCEs (HR = 2.219, 95% CI: 1.425– 3.454, p < 0.001). However, the change of PTX3 level from admission to post-pPCI 5-day had no independently predictive value.Conclusion: The higher increase of PTX3 level 24-hour after pPCI appeared to have a potential value in independently predicting the incidence of 1-year MACCEs in STEMI patients, especially for coronary revascularization.Keywords: pentraxin-3, primary percutaneous coronary intervention, ST-segment elevation myocardial infarction, prognosis

Military Deployment to Southwest Asia and Afghanistan and exposure to toxic airborne particulates has been associated with an increased risk of developing respiratory disease, collectively termed deployment-related respiratory diseases (DRRD). Our knowledge about how particulates mediate respiratory disease is limited, precluding the appropriate recognition or management. Central to this limitation is the lack of understanding of how exposures translate into dysregulated cell identity with dysregulated transcriptional programs. The small airway epithelium is involved in both the pathobiology of DRRD and fine particulate matter deposition. To characterize small airway epithelial cell epigenetic and transcriptional responses to Afghan desert particulate matter (APM) and investigate the functional interactions of transcription factors that mediate these responses, we applied two genomics assays, the assay for transposase accessible chromatin with sequencing (ATAC-seq) and Precision Run-on sequencing (PRO-seq). We identified activity changes in a series of transcriptional pathways as candidate regulators of susceptibility to subsequent insults, including signal-dependent pathways, such as loss of cytochrome P450 or P53/P63, and lineage-determining transcription factors, such as GRHL2 loss or TEAD3 activation. We further demonstrated that TEAD3 activation was unique to APM exposure despite similar inflammatory responses when compared with wood smoke particle exposure and that P53/P63 program loss was uniquely positioned at the intersection of signal-dependent and lineage-determining transcriptional programs. Our results establish the utility of an integrated genomics approach in characterizing responses to exposures and identify genomic targets for the advanced investigation of the pathogenesis of DRRD.

Since the tax of carbon emission is popular and consumers are exhibiting low-carbon preference, a manufacturer may invest to adopt carbon emission reduction (CER) technologies to produce green products. In face of high cost of CER investment and random yield in low carbon production processes for the manufacturer, this paper explores the incentive role of the contracts of revenue-sharing (RS) and cost-sharing with subsidy (CSS) offered by a retailer in a low-carbon supply chain. Theoretical analysis and numerical experiments show that both RS and CSS can promote the manufacturer’s Carbon Emission Reduction (CER) efforts and improve the efficiency of the supply chain, and RS boosts these more than CSS. RS and CSS can also decrease firms’ profit losses due to yield uncertainty, and RS also decreases firms’ profit losses more than CSS. Moreover, to motivate manufacturer’s CER efforts, the government should levy the highest-possible carbon tax under RS, the medium-level carbon tax under CSS, and the lowest-possible carbon tax for the decentralized case, and levy the same carbon tax on the centralized case with that under RS.

While the strong coupling between cavity modes and quantum emitters has been investigated in various systems, multiple surface plasmon modes in single nanostructures strongly coupling with excitons are rarely explored. Here, we investigate the strong coupling between three surface plasmon modes in silver nanowires and excitons in monolayer WSe2 at room temperature. Four plasmon-exciton polariton (plexciton) states are observed in the scattering spectra. The photoluminescence (PL) spectra of the hybrid system show clear splitting due to strong coupling, and the energies of the emission corresponding to the two lower plexciton states agree with that of the scattering very well. In addition, we show that the plasmon-exciton interaction in this system can be efficiently tuned by controlling the excitation power. These results reveal the fundamental properties of strong coupling between multiple plasmon modes and excitons, deepen the understanding of the correlation between scattering and PL spectra of plasmon-exciton strong coupling systems, and open up a new way to actively control the coupling between plasmonic nanostructures and two-dimensional semiconductors.

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here, we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

Objectives This study aimed to describe the pathogen spectrum of bacteria and viruses of RTIs in hospitalized children during the Coronavirus disease 2019 (COVID-19) epidemic in Shenzhen. Methods From October 2020 to October 2021, the results of pathogenic tests causing RTIs were retrospectively analyzed in hospitalized children in Shenzhen Luohu Hospital Group. Results 829 sputum samples for bacterial isolation and 1,037 nasopharyngeal swabs for virus detection in total. The positive detection rate (PDR) of bacteria was 42.1%. Staphylococcus aureus (18.8%) was the predominant bacteria detected in positive cases, with Moraxella catarrhalis (10.9%), Streptococcus pneumoniae (9.5%) following. The PDR of the virus was 65.6%. The viruses ranking first to third were Human Rhinovirus (HRV), Respiratory syncytial virus (RSV), and Human Parainfluenza (HPIV), with rates of 28.0, 18.1, and 13.5%, respectively. Children under 3 years were the most susceptible population to RTIs. The pathogens of S. aureus, M. catarrhalis, S. pneumoniae, HRV, and HPIV were more prevalent in autumn. Meanwhile, RSV had a high rate of infection in summer and autumn. S. aureus and HRV had higher co-infection rates. Conclusions Our findings demonstrate the pathogen spectrum of 1,046 hospitalized children with RTIs in Shenzhen, China, during the COVID-19 outbreak.

The proteolysis targeting chimera (PROTAC) strategy results in the down-regulation of unwanted protein(s) for disease treatment. In the PROTAC process, a heterobifunctional degrader forms a ternary complex with a target protein of interest (POI) and an E3 ligase, which results in ubiquitination and proteasomal degradation of the POI. While ternary complex formation is a key attribute of PROTAC degraders, modification of the PROTAC molecule to optimize ternary complex formation and protein degradation can be a labor-intensive and tedious process. In this study, we take advantage of DNA-encoded library (DEL) technology to efficiently synthesize a vast number of possible PROTAC molecules and describe a parallel screening approach that utilizes DNA barcodes as reporters of ternary complex formation and cooperative binding. We use a designed PROTAC DEL against BRD4 and CRBN to describe a dual protein affinity selection method and the direct discovery of novel, potent BRD4 PROTACs that importantly demonstrate clear SAR. Such an approach evaluates all the potential PROTACs simultaneously, avoids the interference of PROTAC solubility and permeability, and uses POI and E3 ligase proteins in an efficient manner.