Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis.

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.

A Freestanding, Dissolution- and Diffusion-Limiting, Flexible Sulfur Electrode Enables High Specific Capacity at High Mass Loading.

The acquisition of stable and high-areal-capacity S cathodes over 10 mA h cm-2 is a critical and indispensable step to realize the high energy density configuration. However, increasing the areal capacity of S cathodes often deteriorates the specific capacity and stability due to the aggravated dissolution of S and diffusion of solvable polysulfides in the thick electrode. Herein, the design of a freestanding composite cathode that leverages 3D covalent binding sites and chemical adsorption environment to offer dissolution-limiting and diffusion-blocking functions of S species is reported. By employing this architecture, the coin cell exhibits excellent cycling stability and an exceptional specific capacity of 1444.3 mA h g-1 (13 mA h cm-2 ), and the pouch cell configuration manifests a noteworthy areal capacity exceeding 11 mA h cm-2 . This performance is coupled with excellent flexibility, demonstrated through consecutive bending cycle tests, even at a sulfur loading of 9.00 mg cm-2 . This study lays the foundation for the development of flexible Li-S batteries with increased loading capacities and exceptional performance.

Applying AVWEWM to ethical decision-making during autonomous vehicle crashes.

At present, a few scholars studied influencing factors, rules and mechanisms of decision-making in ethical dilemmas. Many factors have been identified, and a few rules and mechanisms have been proposed. However, due to the inability to evaluate the weight and role of each factor in decision-making, it is difficult to establish a computational decision-making model to solve ethical dilemmas. Therefore, entropy weighted method (EWM) and Attribute Value Weighted EWM (AVWEWM) are used to process 84 dilemmas respectively to evaluate the weight and role of each factor in decision-making, then decision-making models based on EWM and AVWEWM are constructed to make decisions during autonomous vehicle (AV) crashes respectively. Lastly, 40 dilemmas are designed to test both decision-making models. The test results indicate that both can make clear decision-making in 40 dilemmas. However, the decision-making by AVWEWM is more consistent with public opinion than EWM. In addition, according to the weight and role of each factor in decision-making, it can also provide a few references for traffic management and legal departments to formulate traffic laws and regulations for AV in the future.

Chaotic phase noise-like encryption based on geometric shaping for coherent data center interconnections.

The network traffic of data centers (DCs) has increased unprecedentedly with the rapid development of digital economy. However, the data transmission faces security threats in the distributed optical interconnection and intensive interaction of DC networks. In this paper, we propose a chaotic phase noise-like encryption algorithm using geometric shaping (GS) for coherent DC interconnections (DCIs). A GS constellation is used to improve transmission performance, and it is combined with coherent equalization algorithms to improve security performance. Then, a chaotic encryption is designed based on phase noise-like transformation (PNLT). The data are effectively scrambled, and the confusion level of phase can be increased. Finally, 216 Gb/s 8-quadrature amplitude modulation (8-QAM) encrypted data are successfully verified on a 240 km transmission link of DCIs. The results show that this scheme can achieve a bit error rate (BER) performance gain of 1.1 dB and provide a highly compatible solution for realizing security enhanced DCIs.

Circ_MAPK9 promotes STAT3 and LDHA expression by silencing miR-642b-3p and affects the progression of hepatocellular carcinoma.

BACKGROUND: Aberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC). METHODS: Circ_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation. RESULTS: The expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression. CONCLUSIONS: Circ_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.

Stacking-induced phonon transport engineering of siligene.

Tunable phonon transport properties of two-dimensional materials are desirable for effective heat management in various application scenarios. Here, we demonstrate by first-principles calculations and Boltzmann transport theory that the lattice thermal conductivity of siligene could be efficiently engineered by forming various stacking configurations. Unlike few-layer graphene, the stacked siligenes are found to be covalently bonded along the out-of-plane direction, which leads to unique dependence of the thermal conductivity on both the stacking order and layer number. Due to the restricted flexural phonon scattering induced by the horizontal reflection symmetry, the AA stacking configuration of bilayer siligene exhibits obviously higher thermal conductivity compared with the AB stacking. In addition, we observe increasing thermal conductivity with the layer number, as evidenced by the reduced phonon scattering phase space and Grüneisen parameter. Interestingly, the Fuchs-Sondheimer model works well for the thickness-dependent thermal conductivity of stacked siligenes.

Simulation examining the factors influencing capillary wick transport in a refrigerant direct cooling system for power battery packs.

The effectiveness of power battery refrigerant direct cooling systems of electric vehicles incorporating capillary wicks is directly determined by these wicks' transport performance. The Fries-Dreyer equation describes wicking behavior, but there is a significant gap between its predictions and the experimental results as reported in the literature. This work examines the factors influencing transport performance in an unconsolidated capillary wick with spherical particles. A mathematical and physical model is developed, the latter using the COMSOL software platform. Both the developed mathematical form and the numerically simulated results of this model are closer to the experimental results than those obtained using the Fries-Dreyer equation. The simulation results enable optimizing the equilibrium height and capillary time numbers providing a fitted Fries-Dreyer equation that is then used to analyze the influence of saturation, inclination angle, wick particle diameter, and tortuosity on the liquid rise mass and velocity and the equilibrium height, and the effects are in close but not perfect accord with experimental data. To narrow the gap, the Fries-Dreyer equation is further optimized using the numerically simulated results, substantially improving the accord with the experimental results.

Mitigating ammonia volatilization in rice cultivation: The impact of partial organic fertilizer substitution.

Optimizing water and nitrogen management to minimize NH3 volatilization from paddy fields has been extensively studied. However, there is limited research on the combined effect of different rates of organic fertilizer substitution (OFS) and irrigation methods in rice cultivation, exploring an effective water and nitrogen combination is beneficial to mitigate NH3 volatilization. To address this gap, we conducted a two-year field experiment to investigate NH3 volatilization under different OFS rates (0%, 25%, and 50%) combined with continuous flooding irrigation (CF) and alternate wet and dry irrigation (AWD). Our findings revealed that NH3 fluxes exhibited similar emission patterns after each fertilization event and significantly decreased with increasing rates of OFS during the basal stage. Compared to no substitution (ON0), the low (ON25) and high (ON50) rates of OFS reduced cumulative NH3 emissions by 18.9% and 16.6%, and lowed NH3 emission factors (EFs) by 26.7% and 23.3%, respectively. Although OFS resulted in a slight reduction in rice yield, yield-scaled NH3 emissions were significantly reduced by 11.9% and 6.5% under the low and high substitution rates, respectively. This reduction was mainly attributed to the slight yield reduction observed at the low substitution rate. Furthermore, when combined with ON0, AWD irrigation had the potential to increase NH3 volatilization. However, this increase was not observed when combined with ON25 and ON50. During each fertilization stage, floodwater + concentration emerged as the prominent environmental factor influencing NH3 volatilization, showing a stronger and more positive correlation compared to other factors such as floodwater pH, soil pH, and NH4+ concentration. Based on our findings, we recommend implementing effective water and nitrogen management strategies to minimize NH3 volatilization in rice cultivation. This involves applying a lower rate of organic fertilizer substitution during the basal stage, maintaining high water levels during fertilization, and implementing mild AWD irrigation during non-fertilization periods.

A non-toxic recombinant Clostridium septicum α toxin induces protective immunity in mice and rabbits.

Clostridium septicum alpha toxin (CSA) plays significant roles in ruminant's braxy. Genetically engineered CSA has been shown to function as a potential vaccine candidate in the prevention of the disease caused by Clostridium septicum. In the present study, we synthesized a non-toxic recombinant, rCSAm4/TMD by introducing four amino acid substitutions (C86L/N296A/H301A/W342A) and 11-amino-acid deletion (residues 212 to 222). Compared to recombinant CSA, rCSAm4/TMD showed no cytotoxicity to MDCK cells and was not fatal to mice. Moreover, rCSAm4/TMD could protect immunized mice against 5 × mouse LD100 (100% lethal dose) of crude CSA without obvious pathological change. Most importantly, rabbits immunized with rCSAm4/TMD produced high titers of neutralizing antibodies which protected the rabbits against crude CSA challenge. These data suggest that genetically detoxified rCSAm4/TMD is a potential subunit vaccine candidate against braxy.

Clostridium perfringens epsilon prototoxin mutant rpETXY30A/Y71A/H106P/Y196A as a vaccine candidate against enterotoxemia.

Epsilon toxin (ETX) is secreted by Clostridium perfringens (C. perfringens)as a relatively inactive prototoxin (pETX), which is enzymatically activated to ETX by removing carboxy-terminal and amino-terminal peptides. Genetically engineered ETX mutants have been shown to function as potential vaccine candidates in the prevention of the enterotoxemia caused by C. perfringens. In the present study, two recombinant site-directed mutants of pETX, rpETXY30A/Y71A/H106P/Y196A (rpETXm41) and rpETXY30A/H106P/Y196A/F199E (rpETXm42), were synthesized by mutating four essential amino acid residues (Tyr30, Tyr71, His106, Tyr196 or Phe199). Compared to recombinant pETX (rpETX), both rpETXm41 and rpETXm42 lacked the detectable toxicity in MDCK cells and mice, which suggested that both rpETXm41 and rpETXm42 are sufficiently safe to be vaccine candidates. Despite the fact that rpETXm41 and rpETXm42 were reactogenic with polyclonal antibodies against crude ETX, both single- and double-dose vaccination (Vs and Vd, respectively) of rpETXm41 induced a higher level of IgG titer and protection in mice than that of rpETXm42. Therefore, we selected rpETXm41 for the further study. Sheep received Vs of 150 µg rpETXm41 developed significant levels of toxin-neutralizing antibodies persisting for at least 6 months, which conferred protection against crude ETX challenge without microscopic lesions. These data suggest that genetically detoxified rpETXY30A/Y71A/H106P/Y196A could form the basis of a next-generation enterotoxemia vaccine.

A combination of organic fertilizers partially substitution with alternate wet and dry irrigation could further reduce greenhouse gases emission in rice field.

Alternate wet and dry (AWD) irrigation and organic fertilizers substitution (OFS) have contrasting effects on CH4 and N2O emissions in rice cultivation. Combining these two practices may be feasible for simultaneous reduction of CH4 and N2O emission from paddy. Hence, we conducted a two-year field experiment to explore the reduction of greenhouse gases under the combination of AWD and OFS. The field experiment which was designed with two irrigation methods (continuous flooding (CF) irrigation and AWD irrigation), and five nitrogen regimes (N0, N135, and N180 represent 0, 135, and 180 kg N ha-1, respectively, ON25 and ON50 represent 25% and 50% OFS for inorganic fertilizer, respectively). The results showed a single-peak emission for CH4 fluxes during the whole rice growing season in all water and nitrogen treatments while the N2O fluxes peak only observed during tillering period with AWD irrigation. AWD irrigation and OFS showed a limited reduction in global warming potential (GWP). These were owing to that AWD irrigation reduced 38.3% CH4 emissions while increase 145.9% N2O emissions when compared to CF irrigation, and the low rate (25%) OFS only reduced CH4 emission by 29.4% while high rate (50%) only reduce N2O emission by 38.8% when compared to conventional inorganic nitrogen fertilizer (N180). Combined AWD and ON25 could maximize the reduction in GWP and yield-scaled GWP, which were reduce 58.0% and 52.5%, respectively, compare to the conventional water and nitrogen management (CF and N180). Furthermore, the structural equation modelling (SEM) indicated that the soil dissolved organic carbon (DOC) and rice aboveground biomass showed a significant positive effect on CH4 fluxes while soil NH4+ with a negative effect, and the soil NH4+, nitrification potential, denitrification potential significant affected N2O fluxes with a positive effect while DOC with a negative effect. These results investigated that 25% OFS rate for inorganic fertilizer could further reduce warming potential in AWD irrigation rice field.

Construction of a Triple-Gene Deletion Mutant of Orf Virus and Evaluation of Its Safety, Immunogenicity and Protective Efficacy.

Contagious ecthyma is a zoonotic disease caused by the orf virus (ORFV). Since there is no specific therapeutic drug available, vaccine immunization is the main tool to prevent and control the disease. Previously, we have reported the construction of a double-gene deletion mutant of ORFV (rGS14ΔCBPΔGIF) and evaluated it as a vaccine candidate. Building on this previous work, the current study reports the construction of a new vaccine candidate, generated by deleting a third gene (gene 121) to generate ORFV rGS14ΔCBPΔGIFΔ121. The in vitro growth characteristics, as well as the in vivo safety, immunogenicity, and protective efficacy, were evaluated. RESULTS: There was a minor difference in viral replication and proliferation between ORFV rGS14ΔCBPΔGIFΔ121 and the other two strains. ORFV rGS14ΔCBPΔGIFΔ121 induced continuous differentiation of PBMC to CD4+T cells, CD8+T cells and CD80+CD86+ cells and caused mainly Th1-like cell-mediated immunity. By comparing the triple-gene deletion mutant with the parental strain and the double-gene deletion mutant, we found that the safety of both the triple-gene deletion mutant and the double-gene deletion mutant could reach 100% in goats, while the safety of parental virus was only 50% after continually observing immunized animals for 14 days. A virulent field strain of ORFV from an ORF scab was used in the challenge experiment by inoculating the virus to the hairless area of the inner thigh of immunized animals. The result showed that the immune protection rate of triple-gene deletion mutant, double-gene mutant, and the parental virus was 100%, 66.7%, and 28.6%, respectively. In conclusion, the safety, immunogenicity, and immune-protectivity of the triple-gene deletion mutant were greatly improved to 100%, making it an excellent vaccine candidate.

Association of Self-Reported Sleep Characteristics and Hip Fracture: Observational and Mendelian Randomization Studies.

Previous observational studies on the relationship between sleep characteristics and fracture have yielded contradictory results. The goal of this study was to replicate the findings in a large longitudinal cohort and then conduct a Mendelian randomization (MR) analysis to infer the causality between sleep behaviors and fracture risk. Based on data from the China Health and Retirement Longitudinal Study (CHARLS) including 17,708 participants, we found that individuals with short sleep duration (<5 h) (OR [odds ratio] = 1.62, 95% CI: 1.07-2.44) or restless sleep (OR = 1.55, 95% CI: 1.10-2.19) have a higher risk of hip fracture. A U-shaped relationship between nighttime sleep duration and hip fracture risk (p-nonlinear = 0.01) was observed using restricted cubic spline regression analysis. Through joint effect analysis, we found that participants with short sleep duration (<5 h) combined with midday napping could significantly decrease hip fracture incidence. We further inferred the causal relationship between self-reported sleep behaviors and hip fracture using the MR approach. Among four sleep phenotypic parameters (sleep duration, daytime napping, chronotype, and insomnia), we found a modest causal relationship between sleep duration and fracture (OR = 0.69, 95% CI: 0.48 to 0.99, p = 0.04). However, no causal relationship was observed for other sleep traits. In conclusion, our findings suggest that short sleep duration has a potential detrimental effect on hip fracture. Improving sleep patterns is of significance for developing hip fracture preventive strategies in the middle-aged and the elderly populations.

High-throughput screening of spike variants uncovers the key residues that alter the affinity and antigenicity of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has elicited a worldwide pandemic since late 2019. There has been ~675 million confirmed coronavirus disease 2019 (COVID-19) cases, leading to more than 6.8 million deaths as of March 1, 2023. Five SARS-CoV-2 variants of concern (VOCs) were tracked as they emerged and were subsequently characterized. However, it is still difficult to predict the next dominant variant due to the rapid evolution of its spike (S) glycoprotein, which affects the binding activity between cellular receptor angiotensin-converting enzyme 2 (ACE2) and blocks the presenting epitope from humoral monoclonal antibody (mAb) recognition. Here, we established a robust mammalian cell-surface-display platform to study the interactions of S-ACE2 and S-mAb on a large scale. A lentivirus library of S variants was generated via in silico chip synthesis followed by site-directed saturation mutagenesis, after which the enriched candidates were acquired through single-cell fluorescence sorting and analyzed by third-generation DNA sequencing technologies. The mutational landscape provides a blueprint for understanding the key residues of the S protein binding affinity to ACE2 and mAb evasion. It was found that S205F, Y453F, Q493A, Q493M, Q498H, Q498Y, N501F, and N501T showed a 3-12-fold increase in infectivity, of which Y453F, Q493A, and Q498Y exhibited at least a 10-fold resistance to mAbs REGN10933, LY-CoV555, and REGN10987, respectively. These methods for mammalian cells may assist in the precise control of SARS-CoV-2 in the future.

Quantitative prediction of the hydraulic performance of free water surface constructed wetlands by integrating numerical simulation and machine learning.

Quantitative prediction of the design parameter-influenced hydraulic performance is significant for optimizing free water surface constructed wetlands (FWS CWs) to reduce point and non-point source pollution and improve land utilization. However, owing to limitations of the test conditions and data scale, a quantitative prediction model of the hydraulic performance under multiple design parameters has not yet been established. In this study, we integrated field test data, mechanism model, statistical regression, and machine learning (ML) to construct such quantitative prediction models. A FWS CW numerical model was established by integrating 13 groups of trace data from field tests. Subsequently, training, test and extension datasets comprising 125 (5^3), 25 (L25(56)) and 16 (L16(44)) data points, respectively, were generated via numerical simulation of multi-level value combination of three quantitative design parameters, namely, water depth, hydraulic loading rate (HLR), and aspect ratio. The short circuit index (φ10), Morrill dispersion index (MDI), hydraulic efficiency (λ) and moment index (MI) were used as representative hydraulic performance indicators. Training set with large samples were analyzed to determine the variation rules of different hydraulic indicators. Based on the control variable method, φ10, λ, and MI grew exponentially with increasing aspect ratio whereas MDI showed a decreasing trend; with increasing water depth, φ10, λ, and MI showed polynomial decreases whereas MDI increased; with increasing HLR, φ10, λ, and MI slowly increased linearly whereas MDI showed the opposite trend. Finally, we constructed models based on multivariate nonlinear regression (MNLR) and ML (random forest (RF), multilayer perceptron (MLP), and support vector regression. The coefficients of determination (R2) of the MNLR and ML models fitting the training and test sets were all greater than 0.9; however, the generalization abilities of different models in the extension set were different. The most robust MLP, MNLR without interaction term, and RF models were recommended as the preferred models to hydraulic performance prediction. The extreme importance of aspect ratio in hydraulic performance was revealed. Thus, gaps in the current understanding of multivariate quantitative prediction of the hydraulic performance of FWS CWs are addressed while providing an avenue for researching FWS CWs in different regions according to local conditions.

Genome-wide identification and characterization of lipoxygenase genes related to the English grain aphid infestation response in wheat.

MAIN CONCLUSION: 44 wheat LOX genes were identified by silico genome-wide search method. TaLOX5, 7, 10, 24, 29, 33 were specifically expressed post aphid infestation, indicating their participation in wheat-aphid interaction. In plants, LOX genes play important roles in various biological progresses including seed germination, tuber development, plant vegetative growth and most crucially in plant signal transduction, stress response and plant defense against plant diseases and insects. Although LOX genes have been characterized in many species, the importance of the LOX family in wheat has still not been well understood, hampering further improvement of wheat under stress conditions. Here, we identified 44 LOX genes (TaLOXs) in the whole wheat genome and classified into three subfamilies (9-LOXs, Type I 13-LOXs and Type II 13-LOXs) according to phylogenetic relationships. The TaLOXs belonging to the same subgroup shared similar gene structures and motif organizations. Synteny analysis demonstrated that segmental duplication events mainly contributed to the expansion of the LOX gene family in wheat. The results of protein-protein interaction network (PPI) and miRNA-TaLOXs predictions revealed that three TaLOXs (TaLOX20, 22 and 37) interacted mostly with proteins related to methyl jasmonate (MeJA) signaling pathway. The expression patterns of TaLOXs in different tissues (root, stem, leaf, spike and grain) under diverse abiotic stresses (heat, cold, drought, drought and heat combined treatment, and salt) as well as under diverse biotic stresses (powdery mildew pathogen, Fusarium graminearum and stripe rust pathogen) were systematically analyzed using RNA-seq data. We obtained aphid-responsive candidate genes by RNA-seq data of wheat after the English grain aphid infestation. Aphid-responsive candidate genes, including TaLOX5, 7, 10, 24, 29 and 33, were up-regulated in the wheat aphid-resistant genotype (Lunxuan144), while they were little expressed in the susceptible genotype (Jimai22) during late response (48 h and 72 h) to the English grain aphid infestation. Meanwhile, qRT-PCR analysis was used to validate these aphid-responsive candidate genes. The genetic divergence and diversity of all the TaLOXs in bread wheat and its relative species were investigated by available resequencing data. Finally, the 3D structure of the TaLOX proteins was predicted based on the homology modeling method. This study not only systematically investigated the characteristics and evolutionary relationships of TaLOXs, but also provided potential candidate genes in response to the English grain aphid infestation and laid the foundation to further study the regulatory roles in the English grain aphid infestation of LOX family in wheat and beyond.

High-throughput saturation mutagenesis generates a high-affinity antibody against SARS-CoV-2 variants using protein surface display assay on a human cell.

As new mutations continue to emerge, the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to evade the human immune system and neutralizing antibodies remains a huge challenge for vaccine development and antibody research. The majority of neutralizing antibodies have reduced or lost activity against SARS-CoV-2 variants. In this study, we reported a novel protein surface display system on a mammalian cell for obtaining a higher-affinity antibody in high-throughput manner. Using a saturation mutagenesis strategy through integrating microarray-based oligonucleotide synthesis and single-cell screening assay, we generated a group of new antibodies against diverse prevalent SARS-CoV-2 variants through high-throughput screening the human antibody REGN10987 within 2 weeks. The affinity of those optimized antibodies to seven prevalent mutants was greatly improved, and the EC50 values were no higher than 5 ng/mL. These results demonstrate the robustness of our screening system in the rapid generation of an antibody with higher affinity against a new SARS-CoV-2 variant, and provides a potential application to other protein molecular interactions.

A non-toxic recombinant bivalent chimeric protein rETXm3CSAm4/TMD as a potential vaccine candidate against enterotoxemia and braxy.

Clostridium perfringens epsilon toxin (ETX) and Clostridium septicum alpha toxin (CSA) are lethal and necrotizing toxins, which play key roles in enterotoxemia and braxy of ruminants, respectively. In the present study, we synthesized a bivalent chimeric protein rETXm3CSAm4/TMD comprising ETXm3 (Y30A/H106P/Y196A) and CSAm4/TMD (C86L/N296A/H301A/W342A and a deletion of residues 212 to 222). Compared with recombinant ETX and recombinant CSA, rETXm3CSAm4/TMD showed no cytotoxicity in Madin-Darby Canine Kidney cells and was not fatal to mice. Moreover, rETXm3CSAm4/TMD could protect immunized mice against 10 × mouse LD100 of crude ETX or 3 × mouse LD100 of crude CSA without obvious histopathologic difference. Most importantly, both rabbits and sheep immunized with rETXm3CSAm4/TMD produced high titers of neutralizing antibody which protected the animals against the challenge with crude ETX or crude CSA. These data suggest that genetically detoxified rETXm3CSAm4/TMD is a potential subunit vaccine candidate against enterotoxemia and braxy.

Direct Monitoring of Li2 S2 Evolution and Its Influence on the Reversible Capacities of Lithium-Sulfur Batteries.

The polysulfide (PS) dissolution and low conductivity of lithium sulfides (Li2 S) are generally considered the main reasons for limiting the reversible capacity of the lithium-sulfur (Li-S) system. However, as the inevitable intermediate between PSs and Li2 S, lithium disulfide (Li2 S2 ) evolutions are always overlooked. Herein, Li2 S2 evolutions are monitored from the operando measurements on the pouch cell level. Results indicate that Li2 S2 undergoes slow electrochemical reduction and chemical disproportionation simultaneously during the discharging process, leading to further PS dissolution and Li2 S generation without capacity contribution. Compared with the fully oxidized Li2 S, Li2 S2 still residues at the end of the charging state. Therefore, instead of the considered Li2 S and PSs, slow electrochemical conversions and side chemical reactions of Li2 S2 are the determining factors in limiting the sulfur utilization, corresponding to the poor reversible capacity of Li-S batteries.

Destructive-Treatment-Free Rapid Polymer-Assisted Metal Deposition for Versatile Electronic Textiles.

Highly conductive, durable, and breathable metal-coated textiles are critical building block materials for future wearable electronics. In order to enhance the metal adhesion on the textile surface, existing solution-based approaches to preparing these materials require time-consuming presynthesis and/or premodification processes, typically in the order of tens of minutes to hours, on textiles prior to metal plating. Herein, we report a UV-induced rapid polymer-assisted metal deposition (r-PAMD) that offers a destructive-treatment-free process to deposit highly conductive metals on a wide variety of textile materials, including cotton, polyester, nylon, Kevlar, glass fiber, and carbon cloth. In comparison to the state of the arts, r-PAMD significantly shortens the modification time to several minutes and is compatible with the roll-to-roll fabrication manner. Moreover, the deposited metals show outstanding adhesion, which withstands rigorous flexing, abrasion, and machine washing tests. We demonstrate that these metal-coated textiles are suitable for applications in two vastly different fields, being wearable and washable sensors, and lithium batteries.