Tumor cell vaccine combined with Newcastle disease virus promote immunotherapy of lung cancer.

Lung cancer is a fatal disease with the highest worldwide morbidity and mortality rates. Despite recent advances in targeted therapy and immune checkpoint inhibitors for cancer, their efficacy remained limited. Therefore, we designed a Newcastle disease virus (NDV)-modified tumor whole-cell vaccine as a therapeutic vaccine and identified its antigen presentation level to develop effective immunotherapy. Then, we calculated the therapeutic and immune-stimulating effects of NDV-modified lung cancer cell vaccine and intratumoral NDV injection combination on tumor-bearing mice. The results showed that the immunogenic cell death (ICD) expression in NDV-modified lung cancer cell vaccine stimulates dendritic cell maturation and T cell activation in vivo and in vitro. Moreover, NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could significantly inhibit tumor growth and enhance the differentiation of Th1 cells and Inflammatory cell infiltration in vivo, leading to an excellent immunotherapeutic effect. Therefore, our results revealed that NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could promote antigen presentation and induce a strong antitumor immune response, which provided a promising combined therapy strategy for tumor immunotherapy.

lncRNA RHPN1-AS1 promotes the progression of endometrial cancer through the activation of ERK/MAPK pathway.

AIM: This study aimed to investigate the function of long noncoding RNA RHPN1 antisense RNA 1 (lncRNA RHPN1-AS1) in the progression of endometrial cancer (EC) and its underlying molecular mechanisms. METHODS: The RHPN1-AS1 expression was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in EC tissues and cells. The cell clones, proliferation, cell cycle, apoptosis, migration and invasion in Ishikawa and HEC-1A cells were respectively measured by colony formation assay, cell counting kit-8 assay (CCK-8) assay, flow cytometry, wound healing assay and transwell assay. In addition, the protein expressions in Ishikawa and HEC-1A cells were measured using western blot and Immunofluorescence assay. RESULTS: Our data showed the RHPN1-AS1 expression was significantly upregulated in both EC tissues and cells. The expression of RHPN1-AS1 was significantly correlated with FIGO stage, histological grade, and lymph node metastasis. Additionally, silencing RHPN1-AS1 could inhibit proliferation, cell cycle progression, migration and invasion, and also promote apoptosis in Ishikawa and HEC-1A cells. Moreover, silencing RHPN1-AS1 could markedly elevate the expressions of caspase-3 and Bax, but reduce the Bcl-2 expression in Ishikawa and HEC-1A cells. We also found that silencing RHPN1-AS1 could significantly inhibit the phosphorylation of MEK and ERK in Ishikawa and HEC-1A cells. After U0126 pretreatment, the inhibition effect of silencing RHPN1-AS1 on the phosphorylation of MEK and ERK was strengthened. CONCLUSION: Our study demonstrated that RHPN1-AS1 could facilitate cell proliferation, migration and invasion, as well as inhibit apoptosis via activating ERK/MAPK pathway in EC.

Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases.

Human cytomegalovirus (HCMV) belongs to the ß-herpesvirus family, which is transmitted in almost every part of the world and is carried by more than 90% of the general population. Increasing evidence indicates that HCMV infection triggers numerous diseases by disrupting the normal physiological activity of host cells, particularly apoptosis. Apoptosis disorder plays a key role in the initiation and development of multiple diseases. However, the relationship and molecular mechanism of HCMV-related diseases and apoptosis have not yet been systematically summarized. This review aims to summarize the role of apoptosis in HCMV-related diseases and provide an insight into the molecular mechanism of apoptosis induced by HCMV infection. We summarize the literature on HCMV-related diseases and suggest novel strategies for HCMV treatment by regulating apoptosis.

Uptake and Translocation of Styrene Maleic Anhydride Nanoparticles in Murraya exotica Plants As Revealed by Noninvasive, Real-Time Optical Bioimaging.

This work reports the in vivo uptake and translocation of PNPs in the one-year grown terrestrial plant, Murraya exotica ( M. exotica), as investigated by two-photon excitation and time-resolved (TPE-TR) optical imaging with a large field of view (FOV, 32 × 32 mm2) in a noninvasive and real-time manner. The PNPs (⟨ Rh⟩ = 12 ± 4.5 nm) synthesized from poly(styrene- co-maleic anhydride) (SMA) were Eu-luminescence labeled (λL ≈ 617 nm). On exposing the roots of living M. exotica plants to the colloidal suspension of SMA PNPs at different concentrations, the spatiotemporal evolution of SMA PNPs along plant stems (60 mm in length) were monitored by TPE-TR imaging, which rendered rich information on the uptake and translocation of PNPs without any interference from the autofluorescence of the plant tissues. The TPE-TR imaging combined with the high-resolution anatomy revealed an intercell-wall route in the lignified epidermis of M. exotica plants for SMA PNP uptake and translocation, as well as the similar accumulation kinetics at different positions along the plant stems. We modeled the accumulation kinetics with Gaussian distribution to account for the trapping probability of a SMA PNP by the lignified cell walls, allowing the statistical parameters, the average trapping time ( tm) and its variance (σ), to be derived for the quantification of the PNP accumulation in individual plants. The TPE-TR imaging and the analysis protocols established herein will be helpful in exploring the mechanism of plant-PNP interaction under physiological condition.

Isolation and identification of uric acid-dependent Aciduricibacillus chroicocephali gen. nov., sp. nov. from seagull feces and implications for hyperuricemia treatment.

Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XBT, a uric acid-degrading bacterium, from black-headed gull (Chroicocephalus ridibundus) feces. Using a polyphasic taxonomic approach, strain 44XBT was identified as a novel genus within the family Bacillaceae; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XBT had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (pucL, pucM, uraD, and allB) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%-99.70% amino acid identity. In vivo experiments revealed that 44XBT reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT. IMPORTANCE: The increasing disease burden of hyperuricemia highlights the need for new therapeutic drugs and treatment strategies. Our study describes the developmental and application values of natural uric acid-degrading bacteria found in the gut of birds and broadened the source of bacteria with potential therapeutic value. Furthermore, the special physiology characteristics and genomic features of strain 44XBT are valuable for further study.

HCMV IE1/IE1mut Therapeutic Vaccine Induces Tumor Regression via Intratumoral Tertiary Lymphoid Structure Formation and Peripheral Immunity Activation in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM.

Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease in Transgenic Mice.

    Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells. / æ–°åŸŽç–«ç— æ¯’é€šè¿‡æŠ‘åˆ¶æ ‘çªçŠ¶ç»†èƒžç™½ä»‹ç´ 12的表达抑制抗原递呈.

As a potential vectored vaccine, Newcastle disease virus (NDV) has been subject to various studies for vaccine development, while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation. To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells (DCs) and T cells, DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide (LPS) for further detection by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunoblotting, and quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed that NDV infection resulted in the inhibition of interleukin (IL)-12p40 in DCs through a p38 mitogen-activated protein kinase (MAPK)|-dependent manner, thus inhibiting the synthesis of IL-12p70, leading to the reduction in T cell proliferation and the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-6 induced by DCs. Consequently, downregulated cytokines accelerated the infection and viral transmission from DCs to T cells. Furthermore, several other strains of NDV also exhibited inhibitory activity. The current study reveals that NDV can modulate the intensity of the innate|‒|adaptive immune cell crosstalk critically toward viral invasion improvement, highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

HCMV-IE2 promotes atherosclerosis by inhibiting vascular smooth muscle cells' pyroptosis.

Atherosclerosis is still the main cause of death in developed and developing countries. Vascular smooth muscle cells (VSMCs) death disorder is a key pathogens of atherosclerosis. During the early stage of human cytomegalovirus (HCMV) infection, immediate early protein 2 (IE2) is critical in regulating its host cell death to ensure HCMV replication. Abnormal cell death induced by HCMV infection contributes to the development of numerous diseases, including atherosclerosis. Hitherto, the underlying mechanism of HCMV involved in the progression of atherosclerosis is still unclear. In this study, the infection models in vitro and in vivo were constructed to explore the pathogenesis of HCMV-related atherosclerosis. Our results indicated that HCMV could contribute to the progression of atherosclerosis by enhancing the proliferation, invasion, and inhibiting the pyroptosis of VSMCs under inflammatory conditions. Meanwhile, IE2 played a key role in these events. Our present research revealed a novel pathogenesis of HCMV-related atherosclerosis, which might help develop new therapeutic strategies.

Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.

Human Cytomegalovirus IE2 Disrupts Neural Progenitor Development and Induces Microcephaly in Transgenic Mouse.

Human cytomegalovirus (HCMV) is a significant contributor to congenital birth defects. Limited by the lack of animal models, the pathogenesis of neurological damage in vivo caused by HCMV infection and the role of individual viral genes remain to be elucidated. Immediate early (IE2) protein may play a function in neurodevelopmental problems caused by HCMV infection. Here, this study intended to investigate IE2's long-term effects on development of the brain in IE2-expressing transgenic mice (Rosa26-LSL-IE2+/-, Camk2α-Cre) aimed to observe the phenotype of postnatal mice. The expression of IE2 in transgenic mice was confirmed by PCR and Western blot technology. We collected mouse brain tissue at 2, 4, 6, 8, and 10 days postpartum to analyze the developmental process of neural stem cells by immunofluorescence. We discovered that transgenic mice (Rosa26-LSL-IE2+/-, Camk2α-Cre) can reliably produce IE2 in the brain at various postpartum phases. Furthermore, we also observed the symptoms of microcephaly in postnatal transgenic mice, and IE2 can damage the amount of neural stem cells, prevent them from proliferating and differentiating, and activate microglia and astrocytes, creating an unbalanced environment in the brain's neurons. In conclusion, we demonstrate that long-term expression of HCMV-IE2 can cause microcephaly through molecular mechanisms affecting the differentiation and development of neural stem cells in vivo. This work establishes a theoretical and experimental foundation for elucidating the molecular mechanism of fetal microcephaly brought by HCMV infection in throughout the period of neural development of pregnancy.

CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses.

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice.

Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis.

BACKGROUND: Acute myelitis (AM) can lead to sudden sensory, motor and autonomic nervous dysfunction, which negatively affects their daily activities and quality of life, so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease. AIM: To investigate the effect of ganglioside (GM) combined with methylprednisolone sodium succinate (MPSS) on the curative effect and neurological function of patients with AM. METHODS: First, we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality, with 52 patients receiving gamma globulin (GG) + MPSS and 56 patients receiving GM + MPSS, assigned to the control group (Con) and observation group (Obs), respectively. The therapeutic effect, neurological function (sensory and motor function scores), adverse events (AEs), recovery (time to sphincter function recovery, time to limb muscle strength recovery above grade 2, and time to ambulation), inflammatory factors (IFs) [interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor (TNF)-α] and other data of the two groups were collected for evaluation and comparison. RESULTS: The Obs had: (1) A significantly higher response rate of treatment than the Con; (2) Higher scores of sensory and motor functions after treatment that were higher than the baseline (before treatment) and higher than the Con levels; (3) Lower incidence rates of skin rash, gastrointestinal discomfort, dyslipidemia, osteoporosis and other AEs; (4) Faster posttreatment recovery of sphincter function, limb muscle strength and ambulation; and (5) Markedly lower posttreatment IL-6, CRP and TNF-α levels than the baseline and the Con levels. CONCLUSION: From the above, it can be seen that GM + MPSS is highly effective in treating AM, with a favorable safety profile comparable to that of GG + MPSS. It can significantly improve patients' neurological function, speed up their recovery and inhibit serum IFs.

CRM197-conjugated multi antigen dominant epitope for effective human cytomegalovirus vaccine development.

Human cytomegalovirus (HCMV) infection is a major cause of neonatal neurodevelopmental disorders and serious complications in organ transplantation. Previous HCMV vaccines focused on humoral immunity but had limited effect on viral infection. T-cell responses are essential to prevent HCMV infection, indicating that effective vaccines require T cells activation. In this study, we designed a novel polypeptides vaccine conjugated to a CRM197 carrier protein, encoding 15 CD8+ T-cell epitopes, five CD4+ T-cell epitopes, and four B-cell epitopes from gB287-320 and pp150311-325 of HCMV to induce T-cell immune responses. To evaluate the effectiveness of vaccines, we subsequently measured the expression of surface molecule markers and proinflammatory cytokines from antigen presenting cells in vivo and in vitro as well as the activation of T cells and antibodies. The results demonstrated that this polypeptide vaccine could activate innate immunity including up-regulating MHCI, II, CD80, CD86, and cytokine expression through the TLR4/NF-κB pathway. Meanwhile, vaccinations elicited potent neutralizing antibody and cellular immune responses producing TNF-α, INF-γ and IL-2, indicating Th1-biased polarization. This finding underlines that CRM197-conjugated polypeptide vaccines facilitate a synergism of humoral and cellular immunity, providing enhanced protection against HCMV, which could be a potential strategy to prevent CMV-associated diseases.

The Relationship between Expression of Nuclear Factor I and the Progressive Occurrence of Diabetic Retinopathy.

The loss of nuclear factor I (NFI) function can lead to defects in Muller's glial differentiation, abnormalities of retinal morphology, and changes in retinal neurons numbers, which are highly involved in diabetic retinopathy (DR). In this study, we addressed the roles of NFIA and NFIB gene expression in the development of DR by using diabetes mellitus (DM) rat models. Retinal histologies were examined, and the expression of NFIA and NFIB at mRNA and protein levels was detected. The results showed that retinal edema and disordered cell arrangement frequently occurred in DR rats. The expressions of NFIA and NFIB in retinal tissue were significantly decreased in DM rats with DR complications. After further inhibiting the expression of NFIA gene in DM rats by using RNA-silencing, majority of DM rats occurred retinopathy and lens fibrosis, which indicated the relationship between decreased expression of NFI and occurrence of retinopathy in DM.

Human Cytomegalovirus Induced Aberrant Expression of Non-coding RNAs.

Human cytomegalovirus (HCMV) is a ß-herpesvirus whose genome consists of double stranded linear DNA. HCMV genome can generate non-coding RNAs (ncRNAs) through transcription in its host cells. Besides that, HCMV infection also changes the ncRNAs expression profile of the host cells. ncRNAs play a key role in maintaining the normal physiological activity of cells, and the disorder of ncRNAs expression has numerous adverse effects on cells. However, until now, the relationship between ncRNAs and HCMV-induced adverse effects are not summarized in detail. This review aims to give a systematic summary of the role of HCMV infection in ncRNAs expression while providing insights into the molecular mechanism of unnormal cellular events caused by ncRNAs disorder. ncRNAs disorder induced by HCMV infection is highly associated with cell proliferation, apoptosis, tumorigenesis, and immune regulation, as well as the development of cardiovascular diseases, and the potential role of biomarker. We summarize the studies on HCMV associated ncRNAs disorder and suggest innovative strategies for eliminating the adverse effects caused by HCMV infection.

Human cytomegalovirus infection and its association with gestational diabetes mellitus during pregnancy.

BACKGROUND: Infection is an important risk factor for gestational diabetes mellitus (GDM), while infection of human cytomegalovirus (HCMV) with GDM remains unclear and rarely reported. This study aimed to investigate the association of HCMV infection and serum inflammatory factor levels in pregnancy with GDM. METHODS: This prospective study included pregnant women who attended at Affiliated Hospital of Qingdao Hospital and Zibo Maternal and Child Health Hospital between December 2018 and August 2020. HCMV specific IgM and serum levels of inflammatory factors, including TNF-α, IL-6, and IL-1ß, were analyzed. RESULTS: A total of 5,316 pregnant women were included (415 with GDM (107 with HCMV+GDM+ and 308 with HCMV-GDM+) and 4901 GDM-free (759 with HCMV+GDM- and 4142 with HCMV-GDM-)). The prevalence of GDM was 7.81%. The rate of activation of HCMV was 16.29%. Specifically, 107 and 759 women in the GDM and control group exhibited HCMV infection, with positive rates of25.78% and 15.48%, respectively (P < 0.01). TNF-α, IL-6, and IL-1ß at 24-28 weeks of gestation were significantly higher in women with GDM and HCMV infection than inthe other groups (all P < 0.01). Multivariable analysis showed that HCMV positive (OR = 1.851; 95% CI [1.425-2.403]; P < 0.001), IL-6 (OR = 1.010; 95% CI [1.002-1.018]; P = 0.013), and IL-1ß (OR = 1.410; 95% CI [1.348-1.474]; P < 0.001) were all significantly correlated with GDM. CONCLUSION: This study suggests HCMV infection during pregnancy is an independent risk factor of GDM and could significantly increase its incidence. Further studies are needed to elucidate possible mechanisms underlying associations between HCMV infection and GDM.

Single-Cell RNA Sequencing of the Nucleus Pulposus Reveals Chondrocyte Differentiation and Regulation in Intervertebral Disc Degeneration.

The nucleus pulposus (NP), a heterogeneous tissue, is an essential functional component of the intervertebral disc. However, NP cell development route and regulation mechanism in intervertebral disc degeneration (IVDD) remain unknown. Here, we performed single-cell RNA sequencing of six NP samples with normal control, mild degeneration, and severe degeneration. Based on unbiased clustering of gene expression patterns from 30,300 single-cell RNA sequencing, we identified three cell lineage families of macrophages, endothelial, and chondrocyte cells and characterized seven chondrocyte subtypes, and defined two developmental pathways of the chondrocyte cell lineage families in the process of IVDD. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocyte cells and other cells in IVDD. Chondrocytes in one of the differentiated orientations interact with macrophages and endothelial cells and have an inflammatory amplification effect, which were key factors causing IVDD. Collectively, these results revealed the dynamic cell landscape of IVDD development and offered new insights into the influence of NP cells differentiation on extracellular matrix homeostasis during degeneration, providing potential treatment targets for IVDD.

Solution combustion derived oxygen vacancy-rich Co3O4 catalysts for catalytic formaldehyde oxidation at room temperature.

Fabricating abundant oxygen vacancies is crucial for non-noble metal oxides to catalyze formaldehyde (HCHO) oxidation at room temperature. Here, a simple one-pot preparation method via solution combustion was found to produce oxygen vacancy-rich Co3O4 catalysts, avoiding delicate defect engineering. The catalyst was evaluated to result in 52% HCHO conversion in a dynamic flow reaction with ∼6 ppm HCHO, which was higher as compared to some other Co3O4 catalysts prepared in three methods of sol-gel, deposition precipitation and thermal decomposition. The optimal catalyst also exhibited high durability with steady HCHO conversion (∼47%) for more than 50 h. The catalyst characterizations revealed that the explosive solution combustion brought out two particular features of Co3O4, namely, the porous network structure with nano-holes and the abundant oxygen vacancies. The latter was demonstrated to increase the reactive oxygen species and to improve the reducibility and the oxygen transport capacity of Co3O4. The two features and the derived properties are beneficial to the activity and durability of Co3O4. The solution combustion method can serve as a simple and feasible way to fabricate abundant oxygen vacancies to provide room-temperature activity of Co3O4 for HCHO elimination at room temperature.