MiR-320 inhibits PRRSV replication by targeting PRRSV ORF6 and porcine CEBPB.

Porcine reproductive and respiratory syndrome (PRRS), a highly contagious disease caused by Porcine reproductive and respiratory syndrome virus (PRRSV), results in huge economic losses to the world pig industry. MiRNAs have been reported to be involved in regulation of viral infection. In our study, miR-320 was one of 21 common differentially expressed miRNAs of Meishan, Pietrain, and Landrace pig breeds at 9-h post-infection (hpi). Bioinformatics and experiments found that PRRSV replication was inhibited by miR-320 through directly targeting PRRSV ORF6. In addition, the expression of CCAAT enhancer binding protein beta (CEBPB) was also inhibited by miR-320 by targeting the 3' UTR of CEBPB, which significantly promotes PRRSV replication. Intramuscular injection of pEGFP-N1-miR-320 verified that miR-320 significantly inhibited the replication of PRRSV and alleviated the symptoms caused by PRRSV in piglets. Taken together, miR-320 have significant roles in the infection and may be promising therapeutic target for PRRS.

Matching Against Men: 5 Years of Residency Match Data Show Disparities Still Exist.

OBJECTIVES: Despite progress toward equal representation by sex in medical practice, women remain underrepresented in many specialties. This study sought to examine the current state of gender equality among recently graduated doctors in multiple specialties. METHODS: Deidentified demographics, standardized examination scores, and Match results were gathered for 829 graduates. Participants were selected from an allopathic medical school between 2016 and 2020. Nineteen students (2.29%) were excluded from the study. Descriptive statistics were calculated, and χ2 tests for independence were used to compare proportions between reported sex and specialty and program Match results. One-way analysis of variance was then performed to test for differences in US Medical Licensing Examination Step 1 and Step 2 scores between sexes. P < 0.05 was considered statistically significant. RESULTS: Of the 829 individuals studied, 44.6% were women. A significantly smaller proportion of women matched into the most competitive specialties, despite no significant difference in US Medical Licensing Examination Step 1 scores between sexes. Furthermore, there was an overall significant trend of women matching into more competitive programs for any given specialty. CONCLUSIONS: In this study, we found that men matched into more highly competitive specialties, whereas women matched into more competitive residency program locations. Further research is needed to determine why women matched into specific specialties at lower rates than their male peers and seek to understand how sex affects the narrative of specialty choice.

The influence of bootleg innovation on individual innovation performance: The mediating effect of cognitive flexibility and the moderating effect of leadership's emotional intelligence.

Based Correctly handling the creativity of employees who have not been adopted is not only conducive to continuously stimulating employees' creativity and improving individual innovation performance, but also conducive to making the best use of organizational resources. This study integrates conservation of resource theory (COR) and social information processing theory to explore the influence of bootleg innovation behavior in organizations on individual innovation performance, as well as the mediating role of cognitive flexibility and the moderating role of leadership emotional intelligence. A three-stage time-lagged research design is used to obtain a valid sample of 327 employees from China. The PROCESS macro for SPSS was applied to test the hypothesized relationships. Findings demonstrated that bootleg innovation is positively related to individual innovation performance; cognitive flexibility mediates the relationship between bootleg innovation and individual innovation performance. Moreover, leadership emotional intelligence moderates the relationship between bootleg innovation and individual innovation performance and between bootleg innovation and cognitive flexibility and between cognitive flexibility and individual innovation performance respectively. The conclusion of the study not only provides a theoretical basis for individuals and leaders to deal with employees' creative abortion, but also provides a new thinking mode for how to maximize the effectiveness of unaccepted ideas and promote individual innovation performance.

CircRNA-5335 Regulates the Differentiation and Proliferation of Sheep Preadipocyte via the miR-125a-3p/STAT3 Pathway.

The content of intramuscular fat (IMF) from preadipocytes is proportional to meat quality in livestock. However, the roles of circRNAs in IMF deposition in sheep are not well known. In this study, we show that circRNA-5335/miR-125a-3p/STAT3 play a crucial adjective role in the proliferation and differentiation of sheep preadipocytes. In this study, we characterized the roles of differentially expressed circRNA-5335/miR-125a-3p/STAT3, which were screened from sheep of different months of age and based on sequencing data. Firstly, the expression profiles of circRNA-5335/miR-125a-3p/STAT3 were identified during the differentiation of preadipocytes in vitro by RT-qPCR and WB. Then, the targeting relationship of the circRNA-5335/miR-125a-3p/STAT3 was verified by dual-luciferase reporter assays. The results of RT-qPCR, CCK8, EdU and Oil Red O staining assay showed that miR-125a-3p suppressed the differentiation and raised the proliferation of preadipocytes by targeting STAT3. As a competing endogenous RNA, the downregulation of circRNA-5335 decreased the expression of STAT3 by increasing miR-125a-3p, which inhibited the differentiation of preadipocytes and promoted proliferation. Our present study demonstrates the functional significance of circRNA-5335/miR-125a-3p/STAT3 in the differentiation of sheep preadipocytes, and provides novel insights into exploring the mechanism of IMF.

Identification and analysis of differentially expressed microRNAs in endometrium to explore the regulation of sheep fecundity.

BACKGROUND: MicroRNAs (miRNAs) play an important regulatory role in mammalian reproduction. Currently, most studies are primarily concentrated on ovarian miRNAs, ignoring the influence of endometrial miRNAs on the fecundity of female sheep. To uncover potential regulators of sheep fecundity, RNA-seq was used to comparatively analyze miRNA expression profiles of endometrium between high prolificacy sheep (HP, litter size = 3) and low prolificacy sheep (LP, litter size = 1) with FecB genotype. RESULTS: Firstly, genomic features of miRNAs from endometrium were analyzed. Furthermore, 58 differentially expressed (DE) miRNAs were found in the endometrium of Hu sheep with different litter size. A co-expression network of DE miRNAs and target genes has been constructed, and hub genes related litter size are included, such as DE miRNA unconservative_NC_019472.2_1229533 and unconservative_NC_019481.2_1637827 target to estrogen receptor α (ESR1) and unconservative_NC_019481.2_1637827 targets to transcription factor 7 (TCF7). Moreover, functional annotation analysis showed that the target genes (NRCAM and NEGR1) of the DE miRNAs were significantly enriched in cell adhesion molecules (CAMs) signaling pathway, which was related to uterine receptivity. CONCLUSION: Taken together, this study provides a new valuable resource for understanding the molecular mechanisms underlying Hu sheep prolificacy.

The Extracellular Vesicle-Macrophage Regulatory Axis: A Novel Pathogenesis for Endometriosis.

Endometriosis (EMs) is a common disease among women whose pathogenesis is still unclear, although there are various hypotheses. Recent studies have considered macrophages the key part of the immune system in developing EMs, inducing inflammation, the growth and invasion of the ectopic endometrium, and angiogenesis. Extracellular vesicles (EVs) as novel intercellular vesicle traffic, can be secreted by many kinds of cells, including macrophages. By carrying long non-coding RNA (lncRNA), microRNA (miRNA), or other molecules, EVs can regulate the biological functions of macrophages in an autocrine and paracrine manner, including ectopic lesion growth, immune dysfunction, angiogenesis, and can further accelerate the progression of EMs. In this review, the interactions between macrophages and EVs for the pathogenesis of EMs are summarized. Notably, the regulatory pathways and molecular mechanisms of EVs secreted by macrophages during EMs are reviewed.

The role of miR-369-3p in proliferation and differentiation of preadipocytes in Aohan fine-wool sheep.

MicroRNAs (miRNAs) are a large class of non-coding RNAs that play important roles in the proliferation and differentiation of adipocytes. Our previous sequencing analysis revealed higher expression of miR-369-3p in the longissimus muscle of 2-month-old Aohan fine-wool sheep (AFWS) compared to 12-month-old sheep (P<0.05), suggesting that miR-369-3p may regulate fat deposition in AFWS. To test this, miR-369-3p mimics, inhibitors, and negative controls (NCs) were constructed and transfected into AFWS preadipocytes. After transfection with miR-369-3p mimics, we found a decrease (P<0.05) in the expression of genes and proteins related to cell proliferation and differentiation, detected by RT-qPCR (quantitative reverse transcription PCR) and western blot analyses. Moreover, EdU (5-ethynyl-2'-deoxyuridine) detection and Oil Red O staining showed a decrease (P<0.05) in cell proliferation and lipid accumulation, respectively. The opposite trends (P<0.05) were obtained after transfection with miR-369-3p inhibitors. In conclusion, the results showed that miR-369-3p can inhibit the proliferation and differentiation of AFWS preadipocytes, providing a theoretical basis to further explore the molecular mechanism of fat deposition in sheep and other domestic animals.

An integrated analysis of mRNAs and lncRNAs in goat's hypothalamus to explore the onset of puberty.

The time of puberty onset is crucial for female animal, as it can affect the generation interval, feeding costs and the utilization of animals. However, little is known about the mechanism of hypothalamic lncRNAs (long noncoding RNAs) in regulatory goat puberty onset. Therefore, genome-wide transcriptome analysis was performed in goats to clarify the roles of hypothalamic lncRNAs and mRNAs in the onset of puberty. In the present study, the co-expression network of differentially expressed (DE) mRNAs in goat hypothalamus identified FN1 as the hub gene, and ECM-receptor interaction, Focal adhesion and PI3K-Akt signalling pathways are involved in puberty. We also observed the crucial hub transcription factors (TCF12, STAT1, STAT2, GATA3 and TEAD4) associated with reproduction and puberty. Then, genetic correlation analysis of DE mRNAs and DE lncRNAs identified the key lncRNAs involved in puberty. This research supplies a resource for transcriptome studies in goat puberty and indicated DE lncRNAs in the ECM-receptor interaction pathway were novel candidate regulators for genetic studies on female reproduction.

A study on the analysis of dynamical transmission behavior and mining key monitoring stations in PM and O3 networks in the Beijing-Tianjin-Hebei region of China.

To investigate the dynamical transmission behavior of pollutants and explore the roles played by monitoring stations in regional air pollutants transportation, we constructed a new model for the dynamical transmission index by adopting a statistics model that employs complex network analysis along with terrain data, meteorological variables, and air quality data. The study is conducted in Beijing-Tianjin-Hebei region with 70 stations in 13 cities. The findings indicated that the regional dynamical transmission networks were characterized by the participation of 67 out of 70 stations, as determined by node number. Among the model characteristics, the average path length and the average clustering coefficient, within the ranges of 2.08-2.32 and 0.26-0.51, respectively, maintained reasonable small-world characteristic. For the seasonal transmission features, the networks for PM2.5, PM10 in winter, and O3 in summer shared similar modeling characteristics with those of yearly networks. This suggested that the networks for these two seasons could represent the yearly transmission features. By employing the entropy weight method, the key monitoring stations numbered 1011 A, 1026 A, and 1010 A, which are located in Tianjin, Shijiazhuang, and Beijing, exerted significant impacts on air pollution transmission path in cities. The novel model has demonstrated its soundness and effectiveness in terms of capturing the behavior of transmission as well as the distinguishing roles of these crucial monitoring stations. This methodology could be employed for the construction of additional monitoring stations, identification of possible pollution sources, and prioritization of key pollution areas, thus providing valuable insights for environmental protection and management.

How firms cope with social crisis: The mediating role of digital transformation as a strategic response to the COVID-19 pandemic.

The COVID-19 pandemic has drawn attention to the strategic responses of Chinese firms on digital transformation and led to a call for enhancing competitive advantage via accelerating digital transformation. Besides the physical health issue, the pandemic has triggered an extraordinary social and economic crisis in which service industries have been attacked hard. In this situation, firms are meeting increasing competitive pressure, which urges them to achieve better performance with the help of digital transformation. Based on the technology-organization-environment framework and dynamic capabilities theory, this research proposed two studies with two methods, including a structural equation model and a regression discontinuity design with a fixed-effect model. The findings suggest digital transformation mediates the relationship between competitive pressure and firm performance among Chinese small- and medium-sized enterprises and large firms after the outbreak of COVID-19, respectively. It confirms that digital transformation is a practical strategic decision for Chinese service firms to respond to increasing competitive pressure in the COVID-19 pandemic. Besides, the results also illustrate the moderating effects of absorptive, innovative, and adaptive capability on the relationship between digital transformation and firm performance among large firms.

Replacing the tropolonic methoxyl group of colchicine with methylamino increases tubulin binding affinity with improved therapeutic index and overcomes paclitaxel cross-resistance.

AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.

Multiplication of defective Ebola virus in a complementary permissive cell line.

In an effort to develop safe and innovative in vitro models for Ebola virus (EBOV) research, we generated a recombinant Ebola virus where the glycoprotein (GP) gene was substituted with the Cre recombinase (Cre) gene by reverse genetics. This defective virus could multiply itself in a complementary permissive cell line, which could express GP and reporter protein upon exogenous Cre existence. The main features of this novel model for Ebola virus are intact viral life cycle, robust virus multiplication and normal virions morphology. The design of this model ensures its safety, excellent stability and maneuverability as a tool for virology research as well as for antiviral agent screening and drug discovery, and such a design could be further adapted to other viruses.

A novel and ultrasensitive fluorescent probe derived from labeled carbon dots for recognitions of copper ions and glyphosate.

Labeling materials with special functional groups are very valuable for the creation of novel probes. Hence, a novel fluorescent probe was constructed by conjugating 4-butyl-3-thiosemicarbazide (BTSC) with carbon dots (CDs). The CDs labeled by BTSC (BTSC-CDs) displayed a strong capability for recognition of Cu2+ and Cu2+ could quench the emission of BTSC-CDs significantly. The fluorescence quenching was proved to be a static quenching which was resulted from the interaction between BTSC-CDs and Cu2+ to form a ground-state BTSC-CDs/Cu2+complex, and the fluorescence intensities showed a good linear correlation with Cu2+ concentrations in the range of 0.20-30 µM. What is more important, by adding glyphosate into the sensor system of BTSC-CDs/Cu2+ the fluorescence of the probe turned on again owing to the stronger chelating between glyphosate and Cu2+ than between BTSC-CDs and Cu2+. This could realize the specific detection of glyphosate and the limit of detection was low to 0.27 µM. Detecting glyphosate using the complex BTSC-CDs/Cu2+ system in actual samples with satisfactory outcomes indicated that a novel fluorescent probe for Cu2+ and subsequent glyphosate detections has been provided.

Objective Activity Parameters Track Patient-specific Physical Recovery Trajectories After Surgery and Link With Individual Preoperative Immune States.

OBJECTIVE: The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established. BACKGROUND: Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. Although phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity. METHODS: Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a 'clock of postoperative recovery'), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients' preoperative immune state. RESULTS: The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, 6 distinct domains of physical function and sleep are identified to represent the objective temporal patterns: ''activity capacity'' and ''moderate and overall activity (declined immediately after surgery); ''sleep disruption and sedentary activity (increased after surgery); ''overall sleep'', ''sleep onset'', and ''light activity'' (no clear changes were observed after surgery). These patterns can be linked to individual patients preopera-tive immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in monocytic myeloid-derived suppressor cells predicted a slower recovery. CONCLUSIONS: Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.

RNF185 regulates proteostasis in Ebolavirus infection by crosstalk between the calnexin cycle, ERAD, and reticulophagy.

Virus infection affects cellular proteostasis and provides an opportunity to study this cellular process under perturbation. The proteostasis network in the endoplasmic reticulum (ER) is composed of the calnexin cycle, and the two protein degradation pathways ER-associated protein degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD/ER-phagy/reticulophagy). Here we show that calnexin and calreticulin trigger Zaire Ebolavirus (EBOV) glycoprotein GP1,2 misfolding. Misfolded EBOV-GP1,2 is targeted by ERAD machinery, but this results in lysosomal instead of proteasomal degradation. Moreover, the ER Ub ligase RNF185, usually associated with ERAD, polyubiquitinates EBOV-GP1,2 on lysine 673 via ubiquitin K27-linkage. Polyubiquinated GP1,2 is subsequently recruited into autophagosomes by the soluble autophagy receptor sequestosome 1 (SQSTM1/p62), in an ATG3- and ATG5-dependent manner. We conclude that EBOV hijacks all three proteostasis mechanisms in the ER to downregulate GP1,2 via polyubiquitination and show that this increases viral fitness. This study identifies linkages among proteostasis network components previously thought to function independently.

miRNA let-7 family regulated by NEAT1 and ARID3A/NF-κB inhibits PRRSV-2 replication in vitro and in vivo.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry worldwide. To investigate the role of miRNAs in the infection and susceptibility of PRRS virus (PRRSV), twenty-four miRNA libraries were constructed and sequenced from PRRSV-infected and mock-infected Porcine alveolar macrophages (PAMs) of Meishan, Landrace, Pietrain and Qingping pigs at 9 hours post infection (hpi), 36 hpi, and 60 hpi. The let-7 family miRNAs were significantly differentially expressed between PRRSV-infected and mock-infected PAMs from 4 pig breeds. The let-7 family miRNAs could significantly inhibit PRRSV-2 replication by directly targeting the 3'UTR of the PRRSV-2 genome and porcine IL6, which plays an important role in PRRSV replication and lung injury. NEAT1 acts as a competing endogenous lncRNA (ceRNA) to upregulate IL6 by attaching let-7 in PAMs. EMSA and ChIP results confirmed that ARID3A could bind to the promoter region of pri-let-7a/let-7f/let-7d gene cluster and inhibit the expression of the let-7 family. Moreover, the NF-κB signaling pathway inhibits the expression of the let-7 family by affecting the nuclear import of ARID3A. The pEGFP-N1-let-7 significantly reduced viral infections and pathological changes in PRRSV-infected piglets. Taken together, NEAT1/ARID3A/let-7/IL6 play significant roles in PRRSV-2 infection and may be promising therapeutic targets for PRRS.

Identification and characterization of unique and common lncRNAs and mRNAs in the pituitary, ovary, and uterus of Hu sheep with different prolificacy.

LncRNAs are regarded as regulators in various animal reproductive physiological processes. However, the regulation of lncRNAs in the reproductive organ development of Hu sheep with different prolificacy remains unknown. Herein, numerous tissue-unique and -common differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs), and fecundity-unique DELs and DEGs were identified among different comparison groups at horizontal and vertical levels. Moreover, the tissue-unique and -common, and fecundity-unique female reproduction-associated DEGs and DELs were screened, and the interaction networks were constructed. Furthermore, MSTRG.43442.1 was mainly present in the cytoplasm of tested cells. The key genes ADAMTS1 and DCN were mainly localized in the granulosa cells, pituitary cells and/or endometrial epithelial cells of ovary, pituitary and/or uterus. Overall, this study identified large numbers of unique and common DELs and DEGs in the female reproductive organs of Hu sheep with different prolificacy and provided new insights into understanding the regulation of Hu sheep fecundity.

Functional characterization of secologanin synthase-like homologous genes suggests their involvement in the biosynthesis of diverse metabolites in the secoiridoid biosynthetic pathway of Camptotheca acuminata Decne.

The assignment of functions based on homology has recently been challenged by the frequent discovery of functional divergence among homologous gene family members of enzymes involved in plant secondary metabolism. Secologanin synthase (SLS) is the key CYP450 enzyme that acts critically in the biosynthesis of Strychnos alkaloid scaffold. In this study, to fully elucidate the mechanism that underlies metabolic variation, the CYP450 paralogs that participate in oxidative transformation of the secoiridoid pathway were functionally characterized by combining multitiered strategies of metabolite profiling, phylogenetic analyses, biochemistry assays and reverse genetics techniques. Five CaSLSs-like homologous genes were mined and isolated from an integrative multi-omics database of Camptotheca acuminata. Protein sequences, structural comparisons, and phylogenetic analyses confirmed that CaSLS1-2 and CaSLS4-5 were grouped into the SLS clade, and only CaSLS3 clustered into the 7DLH clade. Five homologs, including two previously identified enzymatic genes, were thus designated as CaSLAS1, CaSLAS2, Ca7DLH, CaSLS4 and CaSLS5. Enzymatic assays of the recombinant proteins in yeast showed that CaSLAS1 and CaSLAS2 displayed multi-catalytic activities of SLS, secologanic acid synthase (SLAS) and secoxyloganin synthase (SXS). Additionally, the reactions of CaSLASs enzymes generated stereospecific isomers of secoiridoid products, and a new product of secoxyloganin was observed. CaSLS5, a third SLS enzyme isoform that catalyzes the formation of secologanin, was reported for the first time. However, CaSXS enzymatic activities in vitro had little physiological impact on the biosynthesis of camptothecin (CPT) in Camptotheca acuminata. The primary and secondary roles of CaSLSs-like genes in secoiridoid metabolism were confirmed by virus-induced gene silencing (VIGS) in plant leaves. Efficient silencing and transcriptional downregulation of CaSLAS2, compared with the CaSLAS1 homologs, resulted in a greater reduction of the accumulation of CPT within silenced plants, and CaSLS5 had barely any effect on the contents of metabolites in planta. Thus, CaSLAS2, rather than CaSLAS1, appeared to function as a major participant in the biosynthesis of CPT, and there were redundant functions in the CaSLSs-like enzymes. Consistent with such roles, CaSLAS2 was ubiquitously expressed at very high levels in Camptotheca tissues, and CaSLAS2 was specifically expressed in young leaves. In contrast, CaSLS5 was poorly expressed in every tissue tested. Our findings demonstrate that homologs that belong to the CYP72 gene family are functionally diverse and exhibit divergence and thereby uncover an expanding group of enzymatic genes that determine the chemo-diversity of the iridoid pathway.

Visible-Light-Driven Antimicrobial Activity and Mechanism of Polydopamine-Reduced Graphene Oxide/BiVO4 Composite.

In this study, a photocatalytic antibacterial composite of polydopamine-reduced graphene oxide (PDA-rGO)/BiVO4 is prepared by a hydrothermal self-polymerization reduction method. Its morphology and physicochemical properties are characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRD). The results indicate that BiVO4 particles are evenly distributed on the rGO surface. Escherichia coli (E. coli) MG1655 is selected as the model bacteria, and its antibacterial performance is tested by flat colony counting and the MTT method under light irradiation. PDA-rGO/BiVO4 inhibits the growth of E. coli under both light and dark conditions, and light significantly enhances the bacteriostasis of PDA-rGO/BiVO4. A combination of BiVO4 with PDA-rGO is confirmed by the above characterization methods as improving the photothermal performance under visible light irradiation. The composite possesses enhanced photocatalytic antibacterial activity. Additionally, the photocatalytic antibacterial mechanism is investigated via the morphology changes in the SEM images of MG1655 bacteria, 2',7'-dichlorofluorescein diacetate (DCFH-DA), the fluorescence detection of the reactive oxygen species (ROS), and gene expression. These results show that PDA-rGO/BiVO4 can produce more ROS and lead to bacterial death. Subsequently, the q-PCR results show that the transmembrane transport of bacteria is blocked and the respiratory chain is inhibited. This study may provide an important strategy for expanding the application of BiVO4 in biomedicine and studying the photocatalytic antibacterial mechanism.

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0µg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.