Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys.

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

Influencing mechanism of the intellectual capability of big data analytics on the operational performance of enterprises.

In the era of big data, data processing capability is key to gaining a competitive advantage for businesses. With appropriate technical and organizational resources in place, enterprises can extract considerable value from the vast amount of available data, thereby increasing their competitive advantage. Therefore, to utilize big data resources effectively, enterprises should focus on improving the intellectual abilities of big data analysts. Big data analytics intellectual capability (BDAIC) refers to the specialized skills and knowledge that employees of the enterprise possess, including technical, technical management, business, and relational knowledge, that would enable them to use analytics tools to accomplish organizational tasks and shape the core competitiveness of an enterprise. This study constructs a theoretical model that focuses on the mediating role of person-tool fit and examines the mechanisms by which BDAIC affects an enterprise's operational performance. The results show that BDAIC, which contains four basic categories of knowledge, positively influences an enterprise's operational efficiency. Additionally, person-tool matching mediates BDAIC's effect on an enterprise's operational performance. These findings explore the latest avenues of exploration in the research paradigm of big data analytics. Furthermore, this study has important implications for practitioners trying to use big data to improve business performance.

Single-cell transcriptomic atlas of distinct early immune responses induced by SARS-CoV-2 Proto or its variants in rhesus monkey.

Immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play a critical role in the pathogenesis and outcome of coronavirus disease 2019 (COVID-19). However, the dynamic profile of immune responses postinfection by SARS-CoV-2 variants of concern (VOC) is not fully understood. In this study, peripheral blood mononuclear cells single-cell sequencing was performed to determine dynamic profiles of immune response to Prototype, Alpha, Beta, and Delta in a rhesus monkey model. Overall, all strains induced dramatic changes in both cellular subpopulations and gene expression levels at 1 day postinfection (dpi), which associated function including adaptive immune response, innate immunity, and IFN response. COVID-19-related genes revealed different gene profiles at 1 dpi among the four SARS-CoV-2 strains, including genes reported in COVID-19 patients with increased risk of autoimmune disease and rheumatic diseases. Delta-infected animal showed inhibition of translation pathway. B cells, T cells, and monocytes showed much commonality rather than specificity among the four strains. Monocytes were the major responders to SARS-CoV-2 infection, and the response lasted longer in Alpha than the other strains. Thus, this study reveals the early immune responses induced by SARS-CoV-2 Proto or its variants in nonhuman primates, which is important information for controlling rapidly evolving viruses.

[Corrigendum] Tumor suppressor PLZF regulated by lncRNA ANRIL suppresses proliferation and epithelial mesenchymal transformation of gastric cancer cells.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the wound­healing assay data panels featured in Fig. 2E on p. 1011 (namely, the PLZF / 0 h and 48 h data panels for the BGC823 cell line) had also appeared in another article containing a majority of the same authors that had already been published [Chen J­F, Wu P, Xia R, Yang J, Huo X­Y, Gu D­Y, Tang C­J, We D and Yang F: STAT3­induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal­mediated inhibition of autophagy. Mol Cancer 17: 6, 2018], where the same data had been been used to show the results from differently performed experiments. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 2, containing the correct data for the PLZF / 0 h and 48 h data panels in Fig. 2E, is shown on the next page. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 41: 1007­1018, 2019; DOI: 10.3892/or.2018.6866].

Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of the original SARS-CoV-2 strain and its variants of concern (VOCs; including Alpha, Beta, and Delta) in vitro, as well as differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques, were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells, and its VOCs markedly increased the levels of subgenomic RNAs, such as N, Orf9b, Orf6, and Orf7ab, which are known as the innate immune antagonists and the inhibitors of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.

Impact of molar teeth distalization by clear aligners on temporomandibular joint: a three-dimensional study.

BACKGROUND: Maxillary molar distalization is a common technique used in the non-extraction treatment of Angle Class II malocclusion that can effectively correct the molar relationship and create spaces for anterior teeth alignment. However, this approach may also impact the temporomandibular joint (TMJ) due to predictable changes in the posterior vertical dimension. Despite its widespread use, Class II malocclusions correction by molar distalization with clear aligners has not been investigated for their effects on the TMJ. Therefore, this study aimed to analyze the impact of sequential molar distalization using clear aligners on the TMJ. METHODS: Three-dimensional CBCT scans of 23 non-growing patients (7 males, 16 females; mean age 29.8 ± 4.6 years) with skeletal class I or II malocclusion and a bilateral molar class II relationship treated by sequential upper molars distalization with orthodontic clear aligners (Invisalign, Align Technology, San Josè, Ca, USA). A total of 46 joints were examined before and after molar distalization using Anatomage InvivoDental 6.0.3. Linear and angular measurements of the mandibular joint were measured, including joint parameters, inclination, position, and the dimension of the condyle and articular fossa. In addition, 3D volumetric spaces of the joint were analyzed. All data were statistically analyzed by paired T test to determine the differences between the pre-and post-orthodontic procedures. RESULTS: No statistically significant differences were found in all primary effects resulting from maxillary molars distalization by clear aligners on TMJ components measurements and joint spaces between T0 and T1. Meanwhile, statistically significant differences were observed in the linear position of the upper molars and the molar relationship parameter with at least P ≤ 0.05. CONCLUSION: Treatment by sequential upper molars distalization with clear aligners does not lead to significant TMJ parameters changes in condyle and fossa spaces, dimensions, and positions.

SARS-CoV-2 Omicron (B.1.1.529) infection in rhesus macaques, hamsters, and BALB/c mice with severe lung histopathological damage.

Since the first SARS-CoV-2 outbreak in late 2019, the SARS-CoV-2 genome has harbored multiple mutations, especially spike protein mutations. The currently fast-spreading Omicron variant that manifests without symptoms or with upper respiratory diseases has been recognized as a serious global public health problem. However, its pathological mechanism is largely unknown. In this work, rhesus macaques, hamsters, and BALB/C mice were employed as animal models to explore the pathogenesis of Omicron (B.1.1.529). Notably, Omicron (B.1.1.529) infected the nasal turbinates, tracheae, bronchi, and lungs of hamsters and BALB/C mice with higher viral loads than in those of rhesus macaques. Severe histopathological damage and inflammatory responses were observed in the lungs of Omicron (B.1.1.529)-infected animals. In addition, viral replication was found in multiple extrapulmonary organs. Results indicated that hamsters and BALB/c mice are potential animal models for studies on the development of drugs/vaccines and therapies for Omicron (B.1.1.529).

Preparation of Nanocomposites for Antibacterial Orthodontic Invisible Appliance Based on Piezoelectric Catalysis.

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods.

Impact of a staggered scaffold structure on the mechanical properties and cell response in bone tissue engineering.

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered micro-array. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications.

Aryl hydrocarbon receptor is a proviral host factor and a candidate pan-SARS-CoV-2 therapeutic target.

The emergence of a series of SARS-CoV-2 variants has necessitated the search for broad-spectrum antiviral targets. The aryl hydrocarbon receptor (AhR) senses tryptophan metabolites and is an immune regulator. However, the role of AhR in SARS-CoV-2 infection and whether AhR can be used as the target of antiviral therapy against SARS-CoV-2 and its variants are yet unclear. Here, we show that infection with SARS-CoV-2 activates AhR signaling and facilitates viral replication by interfering with IFN-I-driven antiviral immunity and up-regulating ACE2 receptor expression. The pharmacological AhR blockade or AhR knockout reduces SARS-CoV-2 and its variants' replication in vitro. Drug targeting of AhR with AhR antagonists markedly reduced SARS-CoV-2 and its variants' replication in vivo and ameliorated lung inflammation caused by SARS-CoV-2 infection in hamsters. Overall, AhR was a SARS-CoV-2 proviral host factor and a candidate host-directed broad-spectrum target for antiviral therapy against SARS-CoV-2 and its variants, including Delta and Omicron, and potentially other variants in the future.

Aggravated pneumonia and diabetes in SARS-CoV-2 infected diabetic mice.

Multiple clinical and epidemiological studies have shown an interconnection between coronavirus disease 2019 (COVID-19) and diabetes, but experimental evidence is still lacking. Understanding the interplay between them is important because of the global health burden of COVID-19 and diabetes. We found that C57BL/6J mice were susceptible to the alpha strain of SARS-CoV-2. Moreover, diabetic C57BL/6J mice with leptin receptor gene deficiency (db/db mice) showed a higher viral load in the throat and lung and slower virus clearance in the throat after infection than C57BL/6J mice. Histological and multifactor analysis revealed more advanced pulmonary injury and serum inflammation in SARS-CoV-2 infected diabetic mice. Moreover, SARS-CoV-2 infected diabetic mice exhibited more severe insulin resistance and islet cell loss than uninfected diabetic mice. By RNA sequencing analysis, we found that diabetes may reduce the collagen level, suppress the immune response and aggravate inflammation in the lung after infection, which may account for the greater susceptibility of diabetic mice and their more severe lung damage after infection. In summary, we successfully established a SARS-CoV-2 infected diabetic mice model and demonstrated that diabetes and COVID-19 were risk factors for one another.

Composition of the intestinal microbiota of infant rhesus macaques at different ages before and after weaning.

Background: Rhesus macaques and humans are closely related genetically and share similar physiological and pathological characteristics. Exploring the impact of diet on the early establishment of gut microbiota in non-human primates can provide relevant clinical models for healthy infant growth and development. At present, few writers have focused on the composition and changes of the intestinal microbes of infant rhesus macaques throughout their progression from birth to formula feeding after weaning. In this study, we used 16S rRNA sequencing technology to explore the composition of the intestinal flora of rhesus macaques at different ages and analyzed the trends in the microbial changes. Results: The results showed that the relative abundance of Bifidobacterium and Lactobacillus in the intestinal flora of infant rhesus macaques significantly decreased, and Prevotella increased with age. Bifidobacterium longum and Bifidobacterium breve are effective biomarkers to predict grouping. The metabolic pathways enriched in early life mainly concentrated in glycosphingolipid biosynthesis (lacto and neolacto series) and the degradation and metabolism of alcohols and esters. Conclusions: We found that age was an important factor that affected the changes in the intestinal flora. This study revealed the change trend of flora in breastfed and formula-fed infant rhesus monkeys in different growth months, and found that the dominant flora changed greatly. This research provides a medically relevant theoretical basis for understanding the healthy development of infants.

AIM1-dependent high basal salicylic acid accumulation modulates stomatal aperture in rice.

The basal levels of salicylic acid (SA) vary dramatically among plant species. In the shoot, for example, rice contains almost 100 times higher SA levels than Arabidopsis. Despite its high basal levels, neither the biosynthetic pathway nor the biological functions of SA are well understood in rice. Combining with metabolite analysis, physiological, and genetic approaches, we found that the synthesis of basal SA in rice shoot is dependent on OsAIM1, which encodes a beta-oxidation enzyme in the phenylalanine ammonia-lyase (PAL) pathway. Compromised SA accumulation in the Osaim1 mutant led to a lower shoot temperature than wild-type plants. However, this shoot temperature defect resulted from increased transpiration due to elevated steady-state stomatal aperture in the mutant. Furthermore, the high basal SA level is required for sustained expression of OsWRKY45 to modulate the steady-state stomatal aperture and shoot temperature in rice. Taken together, these results provide the direct genetic evidence for the critical role of the PAL pathway in the biosynthesis of high basal level SA in rice, which plays an important role in the regulation of steady-state stomatal aperture to promote fitness under stress conditions.

Exosomal LINC00355 promotes the malignant progression of gastric cancer through histone deacetylase HDAC3-mediated TP53INP1 transcriptional inhibition.

AIMS: Exosomes are a subpopulation of extracellular vesicles (EV) derived from multivesicular body (MVB) that transmit various cellular molecular constituents, including long noncoding RNAs (lncRNAs), to promote intercellular communication. Our aim was to investigate the function and mechanism of exosomal LINC00355 in gastric cancer cells. MAIN METHODS: Exosomal levels of LINC00355 in GC patients and healthy controls were measured by RT-qPCR. The effects of exosomal LINC00355 on GC cell viability, proliferation, migration and invasion were evaluated by CCK8, colony formation, Transwell and wound healing assays. The expression levels of Ki67 in xenograft tumor tissues were confirmed by immunohistochemistry assay, and apoptosis was analyzed by TUNEL apoptosis assay. Western blotting was used to monitor protein expression. RNA immunoprecipitation and RNA pulldown were performed to detect the interaction between LINC00355 and HDAC3. Chromatin immunoprecipitation was used to assess the interaction of HDAC3 with the TP53INP1 promoter. KEY FINDINGS: Exosomal LINC00355 levels were higher in plasma from gastric cancer patients than in plasma from healthy volunteers. Exosomal LINC00355 promoted the proliferation, migration and invasion of gastric cancer cell lines. RNA sequence analysis demonstrated that LINC00355 knockdown downregulated histone deacetylase HDAC3 and upregulated TP53INP1. Mechanistic investigation indicated that exosomal LINC00355 interacted with HDAC3 to suppress TP53INP1 transcription, which promoted epithelial-mesenchymal transition (EMT). SIGNIFICANCE: Exosomal LINC00355 plays a pivotal role in regulating EMT to induce the malignant progression of GC. Exosomal LINC00355 could be a promising biomarker in the early diagnosis and prognosis of GC.

CircLIFR Inhibits Non-small Cell Lung Cancer Progression by Acting as a miR-429 Sponge to Enhance CELF2 Expression.

Lung cancer is the most commonly diagnosed cancer and the leading reason for tumor-related mortality, while non-small cell lung cancer (NSCLC) is the most usual type of lung cancer. Circular RNAs (circRNAs) have emerged as vital regulators in the development of human cancers, including NSCLC. We aimed to explore the functions of circRNA leukemia inhibitory factor receptor (circLIFR) in NSCLC progression. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify the expression of circLIFR, microRNA-429 (miR-429), and Elav-like family member 2 (CELF2) in NSCLC tissues and cells. Cell proliferation capability of NSCLC cells was determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. The flow cytometry assay was performed to evaluate cell-cycle distribution and apoptosis of NSCLC cells. The abilities of migration and invasion were measured by transwell assay. In addition, the activities of caspase 3 and caspase 9 were measured by the assay kits. The interaction relationship between miR-429 and circLIFR or CELF2 was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The expression levels of related proteins were examined by Western Blot assay. The xenograft experiment was established to explore the role of circLIFR in vivo. CircLIFR, circular, and stable transcript in NSCLC cells, was decreased more than 2 folds in NSCLC tissues and cells than controls (P < 0.0001). Importantly, overexpression of circLIFR impeded cell proliferation, migration, invasion, and inactivated protein kinase B (AKT)/phosphatase and tensin homolog (PTEN)-signaling pathways while enhanced apoptosis and cell-cycle arrest in NSCLC cells, which was overturned by upregulation of miR-429 or silencing of CELF2. Furthermore, the upregulation of circLIFR inhibited NSCLC tumor growth in vivo. Overexpression of circLIFR could suppress NSCLC progress by acting as a sponge of miR-429 to regulate the expression of CELF2 and PTEN/AKT-signaling pathways in NSCLC.

3D Finite Element Study of the Physiological Anchorage Control Concept on Anchorage Molars in Lingual Orthodontics.

Objective: To study the effect of the physiological anchorage control concept on anchorage molars in lingual and labial orthodontic techniques. Methods: Three-dimensional finite element models, including the right maxillary first molar, periodontal ligament, alveolar bone, and buccal tube, were established. The models were divided into the McLaughlin-Bennett-Trevisi (MBT™) straight-wire model with 0-degree maxillary first molar axial inclination and the physiologic anchorage Speewire system (PASS) model with -7-degree maxillary first molar axial inclination. Simulated sliding retraction forces (1 N, 1.5 N, and 2 N) were loaded on the buccal side and lingual side, and retraction forces (0.5 N, 0.75 N, and 1 N) were loaded on the buccal and lingual sides simultaneously. The displacements, principal stresses, and von Mises stresses of the periodontal ligament under different conditions were derived. Results: The anchorage molars showed different degrees of rotation, tipping, intrusion, and extrusion. As the force increased, these displacement trends also increased. The mesial displacement of the buccal + lingual force loading was less than that of the other two groups. Under the same force load method, the mesial displacement of the PASS group was less than that of the MBT group. Tilt movement increases the tensile stress of the distal cervical margin and root mesial apical third and the compressive stress of the mesial cervical margin and root distal apical third. The maximum stress of the periodontal ligament was less than that of the other two groups when the lingual force was loaded. Conclusion: The physiological anchorage control concept in lingual orthodontics provides better sagittal anchorage control than in labial orthodontics, but there is no significant difference numerically. Attention should be given to the control of torsion, torque, and arch width. Tilt movement increases the PDL stress of the cervical margin and root apical third. The sliding retraction force should be loaded lingually to maintain the force value of 1∼1.5 N.

LINC02126 is a potential diagnostic, prognostic and immunotherapeutic target for lung adenocarcinoma.

BACKGROUND: Adenocarcinoma has long been an independent histological class of lung cancer, which leads to high morbidity and mortality. We aimed to investigate the contribution of LINC02126 in lung adenocarcinoma. METHODS: RNA sequencing data and clinical information were downloaded. Diagnostic efficiency and survival analysis of LINC02126 were performed, followed by functional analysis of genes co-expressed with LINC02126 and differentially expressed genes (DEGs) in different LINC02126 expression groups. Tumor immune microenvironment (TIME) cell infiltration and correlation analysis of tumor mutation burden were performed in different LINC02126 expression groups. RESULTS: In lung adenocarcinoma, the expression level of LINC02126 was significantly decreased. Significant expression differences of LINC02126 were found in some clinical variables, including T staging, M staging, sex, stage, and EGFR mutation. LINC02126 had potential diagnostic and prognostic value for patients. In the low LINC02126 expression group, the infiltration degree of most immune cells was significantly lower than that in the high LINC02126 expression group. Tumor mutation burden level and frequency of somatic mutation in patients with low LINC02126 expression group were significantly higher than in patients with high LINC02126 expression group. CONCLUSIONS: LINC02126 could be considered as a diagnostic, prognostic and immunotherapeutic target for lung adenocarcinoma.

Intestinal microbial diversity in female rhesus (Macaca mulatta) at different physiological periods.

To explore the relationship between the changes in the physiological period and the fecal microbial population of female rhesus monkeys by measuring microbial composition of fecal samples and the serum hormones. Blood and fecal samples were collected from six female adult rhesus monkeys during the menstrual period (MP), ovulation period (OP), and Luteal period (LP). Serum estradiol (E2) and progesterone (P) levels were determined by the chemiluminescence method and the stool samples were subjected to high-throughput 16S rRNA sequencing. The highest level of E2 and P secretions were during the MP, and LP, respectively. Stool samples produced valid sequences and the number of operational taxonomic unit/OTU was: 810056/3756 (MP), 845242/4159 (OP), 881560/3970 (LP). At the phylum level, the three groups of Firmicutes and Bacteroides accounted for > 95%. The dominant flora at the LP was Bacteroides (53.85%), the dominant flora at the MP and OP was Firmicutes, 64.08 and 56.53%, respectively. At the genus level, the dominant genus at the LP was Prevotella, the dominant genera at the MP were Prevotella, Oncococcus, Streptococcus, and Kurtella. The dominant genera at OP were Prevotella and Nocococcus. At the phylum level, P levels were negatively correlated to Firmicutes, Actinomycetes Actinobacteria, and Fibrobacteres, but positively correlated to Bacteroidetes. Likewise, E2 was positively correlated to Proteobacteria but negatively correlated to Euryarchaeota. At the genus level, P hormone showed a significant correlation with 16 bacterial species, and E2 was significantly correlated to seven bacterial species. Function prediction analysis revealed a high similarity between the MP and OP with six differentially functional genes (DFGs) between them and 11 DFGs between OP and LP (P < 0.05). Fecal microbiota types of female rhesus monkeys varied with different stages of the menstrual cycle, possibly related to changes in hormone levels.

The influencing mechanism of big data analytics technology capability on enterprise's operational performance: The mediating role of data-tool fit.

With the development of network technology, enterprises face the explosive growth of data every day. Therefore, to fully mine the value of massive data, big data analysis (BDA) technology has become the key to developing the core competitiveness of enterprises. However, few empirical studies have investigated the influencing mechanism of the BDA capability of an enterprise on its operational performance. To fill this gap, this study explores how BDA technology capability influences enterprise operation performance, based on dynamic capabilities theory and resource-based theory. It proposes the key variables, including the connectivity, compatibility, and modularization of big data analysis technical capability, enterprise's operational performance, and the fit between data and tools, to establish a model and study the correlation between the variables. The results highlight the mediating role of data-tool fit in the relationships between BDA capability and the enterprise's operational performance, which is a major finding that has not been underlined in the extant literature. This study provides valuable insight for operational managers to help them in mobilizing BDA capability for enterprises' operational management and improving operational performance.

A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant.

The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.