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The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

In recent years, Pb-free CsSnI3 perovskite materials with excellent photoelectric properties as well as low toxicity are attracting much attention in photoelectric devices. However, deep level defects in CsSnI3, such as high density of tin vacancies, structural deformation of SnI6− octahedra and oxidation of Sn2+ states, are the major challenge to achieve high-performance CsSnI3-based photoelectric devices with good stability. In this work, defect passivation method is adopted to solve the above issues, and the ultra-stable and high-performance CsSnI3 nanowires (NWs) photodetectors (PDs) are fabricated via incorporating 1-butyl-2,3-dimethylimidazolium chloride salt (BMIMCl) into perovskites. Through materials analysis and theoretical calculations, BMIM+ ions can effectively passivate the Sn-related defects and reduce the dark current of CsSnI3 NW PDs. To further reduce the dark current of the devices, the polymethyl methacrylate is introduced, and finally, the dual passivated CsSnI3 NWPDs show ultra-high performance with an ultra-low dark current of 2 × 10–11 A, a responsivity of up to 0.237 A W−1, a high detectivity of 1.18 × 1012 Jones and a linear dynamic range of 180 dB. Furthermore, the unpackaged devices exhibit ultra-high stability in device performance after 60 days of storage in air (25 °C, 50% humidity), with the device performance remaining above 90%.

Anaerobic fungus–methanogen co-cultures from rumen liquids and faeces can degrade lignocellulose efficiently. In this study, 31 fungus–methanogen co-cultures were first obtained from the rumen of yaks grazing in Qinghai Province, China, using the Hungate roll-tube technique. The fungi were identified according to morphological characteristics and internal transcribed spacer (ITS) sequences. The methanogens associated with each fungus were identified by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16S rRNA gene sequencing. They were five co-culture types: Neocallimastix frontalis + Methanobrevibacter ruminantium, Neocallimastix frontalis + Methanobrevibacter gottschalkii, Orpinomyces joyonii + Methanobrevibacter ruminantium, Caecomyces communis + Methanobrevibacter ruminantium, and Caecomyces communis + Methanobrevibacter millerae. Among the 31 co-cultures, during the 5-day incubation, the N. frontalis + M. gottschalkii co-culture YakQH5 degraded 59.0%–68.1% of the dry matter (DM) and 49.5%–59.7% of the neutral detergent fiber (NDF) of wheat straw, corn stalk, rice straw, oat straw and sorghum straw to produce CH4 (3.0–4.6 mmol/g DM) and acetate (7.3–8.6 mmol/g DM) as end-products. Ferulic acid (FA) released at 4.8 mg/g DM on corn stalk and p-coumaric acid (PCA) released at 11.7 mg/g DM on sorghum straw showed the highest values, with the following peak values of enzyme activities: xylanase at 12,910 mU/mL on wheat straw, ferulic acid esterase (FAE) at 10.5 mU/mL on corn stalk, and p-coumaric acid esterase (CAE) at 20.5 mU/mL on sorghum straw. The N. frontalis + M. gottschalkii co-culture YakQH5 from Qinghai yaks represents a new efficient combination for lignocellulose biodegradation, performing better than previously reported fungus–methanogen co-cultures from the digestive tract of ruminants.

Background Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. Case presentation A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. Conclusions Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.

A graphene-based flexible filter was obtained via one-step laser heating of a polyimide film. The key parameters of a laser have been confirmed by comparing simulated results and experimental data. High-frequency components of input signals were filtered out effectively for different waveforms, such as sine, rectangular, triangle and pulse waveforms. In order to study filtering performance, this paper focused on amplitude frequency curve, phase frequency curve, transient response and mechanical stability. The phase frequency curve is linear distribution, indicating that it is convenient to control phase shift. The mechanical stability of the device remains good even after 5000 bends, which is unreported in previous work. This paper demonstrated that a graphene-based flexible filter prepared by one-step laser heating has excellent performance and opens new way of thinking about flexible electronics in the future.

All-terrain crane is indispensable for hoisting land wind turbines safely. Because the lifting height, load and lateral dimension during the safe hoisting process of the wind turbine are relatively large, the special jib structure of the all-terrain crane for hoisting wind turbine safely is adopted to solve the problem of interference between the crane jib and the wind power equipment. In view of the unfavorable stress of special jib structure and wind load of special jib structure working environment. On the one hand, the overall finite element model of the all-terrain crane jib for hoisting land wind turbines is established. On the other hand, to combine with the actual load in the lifting process and study the static and nonlinear performance and mode of the boom structure. At last, the mechanical properties of the jib structure are analyzed. This research is very important to improve the safety of wind power lifting.

The driving force for using powder metallurgy (PM) mostly relies on its near net-shape ability and cost-performance ratio. The automotive application is a main market of PM industry, requiring parts with competitive mechanical or functional performance in a mass production scale. As the automobile technology transforms from traditional internal combustion engine vehicles to new energy vehicles, PM technology is undergoing significant changes in manufacturing and materials development. This review outlines the challenges and opportunities generated by the changes in the automotive technology for PM. Low-cost, high-performance and light-weight are critical aspects for future PM materials development. Therefore, the studies on PM lean-alloyed steel, aluminum alloys, and titanium alloy materials were reviewed. In addition, PM soft magnetic composite applied to new energy vehicles was discussed. Then new opportunities for advanced processing, such as metal injection molding (MIM) and additive manufacturing (AM), in automotive industry were stated. In general, the change in automotive industry raises sufficient development space for PM. While, emerging technologies require more preeminent PM materials. Iron-based parts are still the main PM products due to their mechanical performance and low cost. MIM will occupy the growing market of highly flexible and complex parts. AM opens a door for fast prototyping, great flexibility and customizing at low cost, driving weight and assembling reduction.

Background The antitoxin EndoAI is a TA system component that directly inhibits EndoA activity in vitro. The targeted activation of a TA system represents a potentially novel antimicrobial or antiviral strategy. However, whether the antitoxin functions alone and can induce plant disease resistance remain unknown. Results An endoAI was previously identified in the genome of Paenibacillus terrae NK3-4. It underwent a bioinformatics analysis, cloned and expressed in Escherichia coli. Then the functions of EndoAI inducing plant resistance to diseases as an elicitor were evaluated. The results showed that, EndoAI is a stable, alkaline, and hydrophilic protein, with a J-shaped three-dimensional structure in the absence of a ligand. It was clustered on the same branch with an antitoxin from Paenibacillus polymyxa SC2. Ectopically expressed EndoAI triggered a reactive oxygen species burst and a positive hypersensitive response (HR) in tobacco leaves. Moreover, 2 μmol EndoAI induced HR activity in tomato leaf, and it remained active after a 15-min exposure at 4–50 °C, and pH 6–8. Additionally, EndoAI induced plant systemic resistance against Alternaria alternata and tobacco mosaic virus, and the up-regulated transcription of PR genes, including PR1a, PR1b, PR5, PDF1.2, COL1, NPR1, and PAL. Conclusions These results imply that EndoAI may enhance the disease resistance of tobacco by promoting a series of early defense responses and up-regulating PR gene expression. These findings are relevant for future investigations on the mechanism underlying the EndoAI–plant interaction that leads to enhanced disease resistance. Furthermore, the endoAI may be useful for developing effective biocontrol agents to protect plants from diseases. Graphical Abstract

To observe the effect of electroacupuncture (EA) on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in knee joint synovial tissues of rats with rheumatoid arthritis (RA) and to explore the action mechanism of EA on RA. Twelve of the 48 SPF male Sprague-Dawley (SD) rats were assigned to a normal group by the random number table method. The remaining 36 rats were subjected to RA model preparation by intradermal injection of the Freund’s complete adjuvant into the right hind foot pad of each rat under sterile conditions. After the model was successfully prepared, rats were then divided into a model group, a drug group and an EA group according to a random number table method (n=12). Rats in the drug group were treated with 2 mL aqueous solution of tripterygium glycosides [8.1 mg/(kg·bw)]; rats in the EA group were treated with EA at bilateral Yanglingquan (GB 34) and Zusanli (ST 36), for 30 min each time; rats in the normal group and the model group were placed in a special rat fixation tank for 30 min each time, and received the same dose of normal saline as those in the drug group. Rats in all groups received intervention once a day for 4 weeks. Diameter of rat ankle joint and rat arthritis index were measured before and after the intervention. At the end of the experiment, the expressions of phospho-JAK2 and phospho-STAT3 were determined by immunohistochemistry. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect JAK2 and STAT3 mRNAs expressions. After the model was produced, the arthritis index 0.01); immunohistochemical staining cells with phospho-JAK2 and phospho-STAT3 were significantly decreased (all P>0.01); the expression levels of JAK2 and STAT3 mRNAs were decreased with statistical differences (all P>0.01). There were no significant differences between the EA group and the drug group (all P

Nitrilase-mediated biocatalysis reactions have been continuously arousing wide interests by scholars and entrepreneurs in organic synthesis over the past six decades. Since regioselective nitrilases could hydrolyze only one cyano group of dinitriles into corresponding cyanocarboxylic acids, which are virtually impossible by chemical hydrolysis and of interest for a variety of applications, it becomes particularly appealing to synthetic chemists. The aim of the current review is to summarize the recent advancements on regioselective nitrilases concerning their fundamental researches and applications in synthesis of a series of high-value fine chemicals and pharmaceuticals. Carbon chain lengths and substituent group positions of substrates are found to be two crucial factors in affecting regioselectivity of nitrilase. Practical applications of regioselective nitrilases in synthesis of 1,5-dimethyl-2-piperidone (1,5-DMPD), atorvastatin, gabapentin, (R)-baclofen, and (S)-pregabalin were systematically reviewed. Future perspectives clearly elucidating the mechanism of regioselectivity and further molecular modifications of regioselective nitrilases integrating within silico technology for industrial applications were discussed.

A self-healing hydrogel was synthesized via the multi-component reaction of azobenzene-methacrylamide, β-CD and 3-methacrylamido phenylboronic acid. The orthogonal method was applied to analyze the influence of host–guest inclusion complexation, cross-linker and phenylboronic acid monomers content on mechanical properties and healing efficiency of the hydrogel. The results indicated that hydrogel showed autonomic self-healing behavior. The hydrogel demonstrated light-switchable self-healing ability and pH-sensitive swelling ratio. It was found that hydrogel showed high elongation, excellent resilience and low elastic hysteresis. The design of the combined host–guest interactions and boronate esters on the hydrogel showed advantage for improving the mechanical, self-healing and recovery properties simultaneously.

This paper is concerned with the inflow problem for one-dimensional compressible Navier-Stokes equations. For such a problem, Huang, Matsumura, and Shi showed in [4] that there exists viscous shock wave solution to the inflow problem and both the boundary layer solution, the viscous shock wave, and their superposition are time-asymptotically nonlinear stable provided that both the initial perturbation and the boundary velocity are assumed to be sufficiently small. The main purpose of this paper is to show that similar stability results still hold for a class of large initial perturbation which can allow the initial density to have large oscillations. The proofs are given by an elementary energy method and our main idea is to use the smallness of the strength of the viscous shock wave and the boundary velocity to control the possible growth of the solutions induced by the nonlinearity of the compressible Navier-Stokes equations and the inflow boundary condition. The key point in our analysis is to deduce the desired uniform positive lower and upper bounds on the density.

The thermal and mechanical properties of the chemically imidized polyimide (CIPI) films and thermally imidized polyimide (TIPI) films were investigated systematically. Experimental results indicated that the CIPI films show dramatically enhanced tensile strength and modulus with obviously reduced coefficient of thermal expansion (CTE) in comparison with TIPI films. These enhancements results from the high in-plane orientation and close packing of the CIPI backbones. Compared with thermal imidization which starts at about 140 °C, the chemical imidization activated by acetic anhydride and isoquinoline initiates the cyclization even at room temperature. The resulting imide rings restrict the mobility of polymer chains and lead to the in-plane orientation with solvent evaporation. Additionally, fewer small molecules remain in the films after treated at 120 °C by chemical imidization than by thermal imidization. The polymer chain plasticization caused by the evaporation of small molecules at high temperature is obviously restricted. Moreover, the partially imidized polymer inhibits the decomposition of mainchains that occurs at subsequent high temperature process, being beneficial to the formation of high molecular weight PI films. Hence, chemical imidization pathway shows apparent advantage to produce PI films with great combined properties, including high modulus, strength and toughness, as well as high thermal dimension stability etc.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s13577-021-00499-y.

To realize the integrated remediation of SW/GW and soil in the rural river network area, the integrated remediation in rural river network area project (IR-RRNA), funded by the Ministry of Science and Technology of the People’s Republic of China, has been launched. In eastern China, the rural river network area (RRNA) is an anthropic active area characterized by its rapid economic development and high gross national product. However, the water environmental pollution in these areas is increasingly severe, which has greatly hindered their sustainable development. Especially, the frequent interactions between surface/groundwater (SW–GW) have intensified the pollution migration and transformation in RRNA. The IR-RRNA (2019–2022) will apply the related interdisciplinary and methodological knowledge to elucidate the transportation and transformation of pollutants in water and soil during SW–GW interaction and develop remediation technologies of surface water, groundwater, and soil suitable for the RRNA. In this way, to realize the remediation technologies integration for surface/groundwater and soil in RRNA and implementing application demonstration. Meanwhile, a technical guideline will be compiled for the integrated remediation suitable for the RRNA. This project is conducive to addressing the urgent environmental problems as well as promoting rural economic revitalization and ecological environment optimization.

Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes, spermatids, and finally, to mature spermatozoa. This multistage developmental process of spermatogenesis involves the expression of many male germ cell-specific long noncoding RNAs (lncRNAs) and highly regulated and specific gene expression. LncRNAs are a recently discovered large class of noncoding cellular transcripts that are still relatively unexplored. Only a few of them have post-meiotic; however, lncRNAs are involved in many cellular biological processes. The expression of lncRNAs is biologically relevant in the highly dynamic and complex program of spermatogenesis and has become a research focus in recent genome studies. This review considers the important roles and novel regulatory functions whereby lncRNAs modulate mammalian spermatogenesis.

The Piezo1 channel is a mechanotransduction mediator, and Piezo1 abnormalities have been linked to several clinical disorders. However, the role of the Piezo1 channel in cystitis-associated bladder dysfunction has not been documented. The current study aimed to discover the functional role of this channel in regulating bladder activity during cyclophosphamide (CYP)-induced cystitis. One hundred four female rats were randomly assigned to the control, CYP-4h, CYP-48h and CYP-8d groups. CYP successfully induced acute or chronic cystitis in these rats. CYP treatment for 48h or 8d significantly increased Piezo1 channel expression in bladder interstitial Cajal-like cells (ICC-LCs), and the increase in CYP-8d rats was more prominent. In addition, 2.5 μM Grammostola spatulata mechanotoxin 4 (GsMTx4) significantly attenuated bladder hyperactivity in CYP-8d rats by inhibiting the Piezo1 channel in bladder ICC-LCs. Furthermore, by using GsMTx4 and siRNA targeting the Piezo1 channel, we demonstrated that hypotonic stress-induced Piezo1 channel activation significantly triggered Ca2+ and Na+ influx into bladder ICC-LCs during CYP-induced chronic cystitis. In addition, the Piezo1 channel functionally interacted with the relatively activated reverse mode of Na+/Ca2+ exchanger 1 (NCX1) in bladder ICC-LCs from CYP-8d rats. In conclusion, we suggest that the functional role of the Piezo1 channel in CYP-induced chronic cystitis is based on its synergistic effects with NCX1, which can significantly enhance [Ca2+]i and result in Ca2+ overload in bladder ICC-LCs, indicating that the Piezo1 channel and NCX1 are potential novel therapeutic targets for chronic cystitis-associated bladder hyperactivity., Chronic cystitis: proteins may open a channel to treatment A protein that controls the passage of ions through cell membranes is implicated in interstitial cystitis/painful bladder syndrome (IC/PBS). This condition causes chronic pelvic pain and increased urinary frequency and urgency. Current treatment options are unsatisfactory. Researchers led by Longkun Li at the Third Military Medical University in Chongqing, China, and Mingjia Tan at the University of Michigan, Ann Arbor, USA, studied the role of this membrane channel protein, called Piezo1. Increased activity of Piezo1 was linked to bladder hyperactivity in rats with drug-induced cystitis. The research also identified a synergistic interaction between Piezo1 and a second membrane channel protein. A drug that inhibits Piezo1 activity reduced bladder hyperactivity in the rats. Drugs targeting these two proteins might help to treat the chronic cystitis of patients with IC/PBS.