Bispecific antibodies provide broad neutralization of emerging beta-coronaviruses by targeting ACE2 and viral spikes.

Human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 have recurrently emerged as significant pathogens, causing severe respiratory illnesses and presenting challenges to monoclonal antibody therapeutics due to their rapid evolution, particularly the diverse variants of SARS-CoV-2. In this study, we utilized "Knob-into-Hole" and "IgG-scFv" technologies to engineer bispecific antibodies (bsAbs) that target both the viral receptor and spike protein, enhancing their neutralization breadth and potency. Our bsAbs, combining anti-SARS-CoV-2 or anti-MERS-CoV antibodies with an anti-ACE2 antibody, demonstrated effective neutralization across a range of SARS-CoV-2 variants, SARS-CoV and MERS-CoV in both pseudovirus and authentic virus assays. Notably, the "IgG-scFv" bsAbs format exhibited superior binding and neutralization capabilities compared to the "Knob-into-Hole" configurations. The most effective of these, "IgG-scFv" H11B11_m336, displayed exceptional neutralization potency against a panel of 24 pseudotyped Beta-Coronaviruses, with IC50 values ranging from 0.001-0.183 µg/mL. Overall, our findings underscore the potential of bsAbs as an effective strategy to meet the immediate challenges posed by existing and emerging pathogens, thereby enhancing global pandemic preparedness.

Confocal image of three oxoaporphine alkaloids in cancer cell lines and their interaction with DNA by multispectroscopic and molecular docking techniques.

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV-vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine.

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.

A Framework for Measuring Tree Rings Based on Panchromatic Images and Deep Learning.

Tree-ring data are pivotal for decoding the age and growth patterns of trees, reflecting the impact of environmental factors over time. Addressing the significant shortcomings of traditional, labour-intensive and resource-demanding methods, we propose an innovative automated technique that utilizes panchromatic images and deep learning for measuring tree rings. The method utilizes convolutional neural networks to enhance image quality, precisely delineate tree rings through segmentation and perform ring counting and width calculation in the post-processing stage. We compiled an extensive data set from diverse sources, including Beijing Forestry University and the Summer Palace, to train our algorithm. The performance of our method was validated empirically, demonstrating its potential to transform tree-ring analysis and provide deeper insights into ecological and climatological research.

Multifunctional nanofibrous scaffolds for enhancing full-thickness wound healing loaded with Bletilla striata polysaccharides.

The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.

Adsorption mechanism and remediation of heavy metals from soil amended with hyperthermophilic composting products: Exploration of waste utilization.

Due to high humification, hyperthermophilic composting products (HP) show potential for remediating heavy metal pollution. However, the interaction between HP and heavy metals remains unclear. This study investigated the adsorption mechanism and soil remediation effect of HP on heavy metals. The results showed that the maximum adsorption capacity of HP increased by an average of 30.74 % compared to conventional composting products. HP transformed 34.87 % of copper, 42.55 % of zinc, and 35.63 % of lead from exchangeable and reducible forms into residual and oxidizable forms, thus reducing the soil risk level. In conclusion, HP significantly enhanced the adsorption of heavy metals and their transformation from unstable to stable forms, primarily due to the higher content of hydroxyl and carboxyl groups. This study aims to demonstrate the effectiveness of HP for remediating heavy metal pollution and to enhance the understanding of the underlying mechanism, which lays a foundation for waste utilization.

How Daily Job Insecurity Links to Next-Day Ingratiation: The Roles of Emotional Exhaustion and Power Distance Orientation.

Purpose: Numerous empirical studies consistently support the detrimental impact of job insecurity (JI) on employees. However, a new perspective suggests that individuals perceiving JI may proactively take measures to protect their positions. Drawing from the conservation of resources theory, this study argues that perceived resource loss due to JI motivates employees to engage in ingratiating behaviors for expanding their social capital. Additionally, this study empirically establishes the mediating role of emotional exhaustion and the moderating effect of power distance. Methods: A daily diary design was used to examine the relationship between daily JI and next-day ingratiation. Our analyses of data collected from 134 full-time employees across 10 consecutive working days using multi-level model. Results: Our results showed that daily JI was found to affect next-day ingratiation (γ = 0.14, p < 0.01), and this relationship was mediated by emotional exhaustion (indirect effect = 0.07, p < 0.05, 95% CI [0.01, 0.13]). Power distance moderated the relationship between emotional exhaustion and ingratiation (γ = 0.25, p < 0.001), and further moderated the indirect effect of JI on ingratiation via emotional exhaustion. Conclusion: Our study has revealed that JI serves as a catalyst for employees to engage in resource creation behavior, thereby contributing to a deeper understanding of the implications of JI as an independent variable for both scholars and businesses.

Mechanism of Abnormal Activation of MEK1 Induced by Dehydroalanine Modification.

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.

Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection.

The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4+/CD8+ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4+/CD8+ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.

Unlocking the potential of biochar: an iron-phosphorus-based composite modified adsorbent for adsorption of Pb(II) and Cd(II) in aqueous environments and response surface optimization of adsorption conditions.

In this work, iron-phosphorus based composite biochar (FPBC) was prepared by modification with potassium phosphate and iron oxides for the removal of heavy metal ions from single and mixed heavy metal (Pb and Cd) solutions. FTIR and XPS characterization experiments showed that the novel modified biochar had a greater number of surface functional groups compared to the pristine biochar. The maximum adsorption capacities of FPBC for Pb(II) and Cd(II) were 211.66 mg·g-1 and 94.08 mg·g-1 at 293 K. The adsorption of Pb(II) and Cd(II) by FPBC followed the proposed two-step adsorption kinetic model and the Freundlich isothermal adsorption model, suggesting that the mechanism of adsorption of Pb(II) and Cd(II) by FPBC involved chemical adsorption of multiple layers. Mechanistic studies showed that the introduction of -PO4 and -PO3 chemisorbed with Pb(II) and Cd(II), and the introduction of -Fe-O increased the ion exchange with Pb(II) and Cd(II) during the adsorption process and produced precipitates such as Pb3Fe(PO4)3 and Cd5Fe2(P2O7)4. Additionally, the abundant -OH and -COOH groups also participated in the removal of Pb(II) and Cd(II). In addition, FPBC demonstrated strong selective adsorption of Pb(II) in mixed heavy metal solutions. The Response Surface Methodology(RSM) analysis determined the optimal adsorption conditions for FPBC as pH 5.31, temperature 26.01 °C, and Pb(II) concentration 306.30 mg·L-1 for Pb(II). Similarly, the optimal adsorption conditions for Cd(II) were found to be pH 5.66, temperature 39.34 °C, and Cd(II) concentration 267.68 mg·L-1. Therefore, FPBC has the potential for application as a composite-modified adsorbent for the adsorption of multiple heavy metal ions.

Precisely Controlling Polymer Acceptors with Weak Intramolecular Charge Transfer Effect and Superior Coplanarity for Efficient Indoor All-Polymer Solar Cells with over 27% Efficiency.

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.

Designing a Novel Wide Bandgap Small Molecule Guest for Enhanced Stability and Morphology Mediation in Ternary Organic Solar Cells with over 19.3% Efficiency.

In this study, a novel wide-bandgap small molecule guest material, ITOA, designed and synthesized for fabricating efficient ternary organic solar cells (OSCs) ITOA complements the absorbance of the PM6:Y6 binary system, exhibiting strong crystallinity and modest miscibility. ITOA optimizes the morphology by promoting intensive molecular packing, reducing domain size, and establishing a preferred vertical phase distribution. These features contribute to improved and well-balanced charge transport, suppressed carrier recombination, and efficient exciton dissociation. Consequently, a significantly enhanced efficiency of 18.62% for the ternary device is achieved, accompanied by increased short-circuit current density (JSC), fill factor (FF), and open-circuit voltage (VOC). Building on this success, replacing Y6 with BTP-eC9 leads to an outstanding PCE of 19.33% for the ternary OSCs. Notably, the introduction of ITOA expedites the formation of the optimized morphology, resulting in an impressive PCE of 18.04% for the ternary device without any postprocessing. Moreover, the ternary device exhibits enhanced operational stability under maximum power point (MPP) tracking. This comprehensive study demonstrates that a rationally designed guest molecule can optimize morphology, reduce energy loss, and streamline the fabrication process, essential for achieving high efficiency and stability in OSCs, paving the way for practical commercial applications.

Targeted Linked-Read Sequencing for Direct Haplotype Phasing of Parental GJB2/SLC26A4 Alleles: A Universal and Dependable Noninvasive Prenatal Diagnosis Method Applied to Autosomal Recessive Nonsyndromic Hearing Loss in At-Risk Families.

Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. Additionally, the existing method can not be used for challenging genome loci (eg, copy number variations, deletions, inversions, or gene recombinants) or on families without proband genotype. This study assessed the performance of relative haplotype dosage analysis (RHDO)-based NIPD for identifying fetal genotyping in pregnancies at risk of ARNSHL. Fifty couples carrying pathogenic variants associated with ARNSHL in either GJB2 or SLC26A4 were recruited. The RHDO-based targeted linked-read sequencing combined with whole gene coverage probes was used to genotype the fetal cell-free DNA of 49 families who met the quality control standard. Fetal amniocyte samples were genotyped using invasive prenatal diagnosis (IPD) to assess the performance of NIPD. The NIPD results showed 100% (49/49) concordance with those obtained through IPD. Two families with copy number variation and recombination were also successfully identified. Sufficient specific informative single-nucleotide polymorphisms for haplotyping, as well as the fetal cell-free DNA concentration and sequencing depth, are prerequisites for RHDO-based NIPD. This method has the merits of covering the entire genes of GJB2 and SLC26A4, qualifying for copy number variation and recombination analysis with remarkable sensitivity and specificity. Therefore, it has clinical potential as an alternative to traditional IPD for ARNSHL.

Comparative Analysis of Bisexual and Parthenogenetic Populations in Haemaphysalis Longicornis.

Haemaphysalis longicornis, a three-host tick with a wide host range, is widely distributed in different countries and regions. It stands out among ticks due to its unique feature of having both parthenogenetic and bisexual populations. Despite their morphological resemblance, the characteristics of the parthenogenetic population have been overlooked. In this comprehensive study, we systematically compared the similarities and differences between these two populations. Our investigation revealed that the parthenogenetic H. longicornis, widely distributed in China, was found in ten provinces, surpassing the previously reported distribution. Notably, individuals from the parthenogenetic population exhibited a prolonged blood-feeding duration during the larval and nymph stages compared to their bisexual counterparts. Additionally, the life cycle of the parthenogenetic population was observed to be longer. A flow cytometry analysis indicated a DNA content ratio of approximately 2:3 between the bisexual and parthenogenetic populations. A phylogenetic analysis using whole mitochondrial genome sequences resulted in the separation of the phylogenetic tree into two distinct branches. A molecular analysis unveiled a consistent single T-base deletion at nucleotide 8497 in the parthenogenetic population compared to the bisexual population. Both populations displayed high viral infection capability and significant resistance to ivermectin. Intriguingly, despite these differences, the parthenogenetic population exhibited a similar life cycle to the bisexual population, retaining the ability to transmit pathogens such as Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland Virus (HRTV). These findings contribute to a deeper understanding of the distinct characteristics and similarities between different populations of H. longicornis, laying the foundation for future research in this field.

Central precocious puberty in a boy with X-linked adrenoleukodystrophy caused by a novel ABCD1 mutation.

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by pathogenic variants in the ABCD1 gene. The symptoms include primary adrenal insufficiency (PAI), progressive spinal cord disease, inflammatory demyelinating cerebral disease, and primary hypogonadism. It is exceptionally rare that pediatric PAI is accompanied by central precocious puberty (CPP). The purpose of this study was to better understand the diversity of clinical manifestations of X-ALD and to identify the ABCD1 gene mutation in a case of a boy with X-ALD accompanied by CPP. We collected clinical, laboratory and imaging data, and used whole-exome sequencing (WES) analysis to evaluate the pathogenicity of the variant. We also predicted the potential deleterious effects of the novel mutation using Mutation Taster and generated three-dimensional protein structures using Swiss-Model and PyMOL Viewer software. The patient presented with PAI accompanied by CPP. Adrenal gland CT revealed adrenal hypoplasia. Gonadotropin-releasing hormone stimulation tests revealed CPP. WES revealed a novel variant (c.1376dup) in the ABCD1 gene, which resulted in a reading frameshift and a premature termination codon (p.Leu461ProfsTer95). Sanger sequencing confirmed that the variant was inherited from his heterozygous mother. Mutation Taster predicted that the variant could be harmful. The overall three-dimensional structures of the mutant wild-type proteins were visually distinct. Our results shed light on additional aspects of X-ALD. The premature activation of the hypothalamic-pituitary-gonadal axis may possibly be related to the pathogenic ABCD1 gene mutation.

Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination.

The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.

Spillover and spillback: Linking daily job insecurity to next-day counterproductive work behavior.

Spillover effect theory posits that work stressors can have spillover effects into workers' home lives. Although job insecurity spillover into the home domain has been explored extensively, potential spillback effects into the work domain have not. We posit that daily job insecurity represents a negative subjective perception that can spillover into the home domain and lead to insomnia, which will damage the recovery of self-regulatory resources and make employees unable to regulate their own behavior, ultimately resulting in next-day counterproductive work behavior. We hypothesized that self-compassion, as an individual trait, weakens the spillover effect of job insecurity and moderates the indirect effect of job insecurity on next-day counterproductive work behavior via insomnia. Our analyses of data collected from 132 full-time employees across 10 consecutive working days showed that insomnia mediates the relationship between daily job insecurity and next-day counterproductive work behavior, and further showed that this relationship was moderated by self-compassion. Overall, our research captures the cascading effects of daily job insecurity and contributes to a more complete understanding of the spillover effect of job insecurity.

Identification of a novel heterozygous PTH1R variant in a Chinese family with incomplete penetrance.

BACKGROUND: Mutations in PTH1R are associated with Jansen-type metaphyseal chondrodysplasia (JMC), Blomstrand osteochondrodysplasia (BOCD), Eiken syndrome, enchondroma, and primary failure of tooth eruption (PFE). Inheritance of the PTH1R gene can be either autosomal dominant or autosomal recessive, indicating the complexity of the gene. Our objective was to identify the phenotypic differences in members of a family with a novel PTH1R mutation. METHODS: The proband was a 13-year, 6-month-old girl presenting with short stature, abnormal tooth eruption, skeletal dysplasia, and midface hypoplasia. The brother and father of the proband presented with short stature and abnormal tooth eruption. High-throughput sequencing was performed on the proband, and the variant was confirmed in the proband and other family members by Sanger sequencing. Amino acid sequence alignment was performed using ClustalX software. Three-dimensional structures were analyzed and displayed using the I-TASSER website and PyMOL software. RESULTS: High-throughput genome sequencing and Sanger sequencing validation showed that the proband, her father, and her brother all carried the PTH1R (NM_000316) c.1393G>A (p.E465K) mutation. The c.1393G>A (p.E465K) mutation was novel, as it has not been reported in the literature database. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the p.E465K variant was considered to have uncertain significance. Biological information analysis demonstrated that this identified variant was highly conserved and highly likely pathogenic. CONCLUSIONS: We identified a novel heterozygous mutation in the PTH1R gene leading to clinical manifestations with incomplete penetrance that expands the spectrum of known PTH1R mutations.

Enhanced neutralization of SARS-CoV-2 variant BA.2.86 and XBB sub-lineages by a tetravalent COVID-19 vaccine booster.

Emerging SARS-CoV-2 sub-lineages like XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3 and the variant BA.2.86 have recently been identified. Understanding the efficacy of current vaccines on these emerging variants is critical. We evaluate the serum neutralization activities of participants who received COVID-19 inactivated vaccine (CoronaVac), those who received the recently approved tetravalent protein vaccine (SCTV01E), or those who had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Neutralization profiles against a broad panel of 30 sub-lineages reveal that BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibit heightened resistance to neutralization compared to previous variants. However, despite their extra mutations, BA.2.86 and the emerging XBB sub-lineages do not demonstrate significantly increased resistance to neutralization over XBB.1.5. Encouragingly, the SCTV01E booster consistently induces higher neutralizing titers against all these variants than breakthrough infection does. Cellular immunity assays also show that the SCTV01E booster elicits a higher frequency of virus-specific memory B cells. Our findings support the development of multivalent vaccines to combat future variants.

The cross-level effect of team safety-specific transformational leadership on workplace safety behavior: The serial mediating role of team safety climate and team safety motivation.

INTRODUCTION: Workplace safety not only impairs individual health but also affects economic and social development. METHOD: Based on social learning theory, collective social learning theory, and expectancy-valence theory, using cluster random sampling method, 630 employees from 66 different work teams out of around 800 employees in a domestic petroleum enterprise were selected to participate in the research. The safety-specific transformational leadership, safety climate, safety motivation and workplace safety behavior scales were used. Data were collected in two stages. SPSS22.0 and Mplus7.0 were used to analyze the data to explore the relationship between team safety-specific transformational leadership and workplace safety behavior, as well as the serial mediating effect of team safety climate and team safety motivation. RESULTS: The results showed that: (a) team safety-specific transformational leadership can positively influence safety compliance and safety participation; (b) team safety climate mediates the relationship between team safety-specific transformational leadership and safety compliance and safety participation; (c) team safety motivation mediates the relationship between team safety-specific transformational leadership and safety compliance and safety participation; and (d) team safety climate and team safety motivation play a serial mediating role between team safety-specific transformational leadership and safety compliance and safety participation. PRACTICAL APPLICATIONS: This research has both theoretical and practical significance.