A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

The effect of omentoplasty in various surgical operations: Systematic review and meta-analysis.

BACKGROUND: Omentoplasty is commonly used in various surgeries. However, its effectiveness is unsure due to lack of convincing data and research. To clarify the impact of omentoplasty on postoperative complications of various procedures, this systematic review and meta-analysis was performed. METHODS: A systematic review of published literatures from four databases: PubMed, Web of Science, Cochrane Library, and Embase before July 14, 2022. We primarily included publications on five major surgical operations performed in conjunction with omentoplasty: thoracic surgery, esophageal surgery, gastrointestinal surgery, pelvi-perineal surgery, and liver surgery. The protocol was registered in PROSPERO. RESULTS: This review included 25 273 patients from 91 studies (n=9 670 underwent omentoplasty). Omentoplasty was associated with a lower risk of overall complications particularly in gastrointestinal (RR 0.53; 95%CI 0.39-0.72) and liver surgery (RR 0.54; 95%CI 0.39-0.74). Omentoplasty reduced the risk of postoperative infection in thoracic (RR 0.38; 95%CI 0.18-0.78) and liver surgery (RR 0.39; 95%CI 0.29-0.52). In patients undergoing esophageal (RR 0.89; 95%CI 0.80-0.99) and gastrointestinal (RR 0.28; 95%CI 0.23-0.34) surgery with a BMI greater than 25, omentoplasty is significantly associated with a reduced risk of overall complications compared to patients with normal BMI. No significant differences were found in pelvi-perineal surgery, except infection in patients whose BMI ranged from 25 kg/m2 to 29.9 kg/m2 (RR 1.25; 95%CI 1.04-1.50) and anastomotic leakage in patients aged over 60 (RR 0.59; 95%CI-0.39-0.91). CONCLUSION: Omentoplasty can effectively prevent postoperative infection. It is associated with a lower incidence of multiple postoperative complications in gastrointestinal and liver surgery.

Adipose stem cells control obesity-induced T cell infiltration into adipose tissue.

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.

The first Chinese intellectual developmental disorder, autosomal recessive 57 patient with two novel MBOAT7 variants.

BACKGROUND: Intellectual disability (ID) is a con neurodevelopmental disorder in children. The genetic etiology of ID is complex, but more subtypes are defined due to the broad application of next-generation sequencing. METHODS: Whole-exome sequencing (WES) and Sanger sequencing was applied in a family with ID. RESULTS: We report a Chinese 7.5-year-old boy, born to non-consanguineous parents. He showed severe intellectual disability, seizures and autistic features. Two previously unreported variants in MBOAT7, c.669C>G (p.(Tyr223*)) and c.1095C>G (p.(Ser365Arg)) were identified by trio-WES. His mother is a heterozygous carrier of the c.1095C>G variant. The c.669C>G variant is a de novo variant which was undetected in his parents. By construction of the full-length cDNA of the patient's MBOAT7, we verified that these two variants were trans-compound heterozygous variants, which support the genetic etiology of this patient. CONCLUSION: This patient is the first Chinese case of intellectual developmental disorder (IDD), autosomal recessive 57 (OMIM:617188) with two unreported MBOAT7 variants.

The investigation of thrombocytopenia after transcatheter occlusion of patent ductus arteriosus.

OBJECTIVE: To investigate the risk factors for thrombocytopenia after transcatheter occlusion operation of patent ductus arteriosus (PDA). METHOD: Retrospective analyses were conducted using clinical data from 106 patients with PDA who underwent transcatheter closure operations at Henan Provincial Chest Hospital, Zhengzhou University, from January 2018 to June 2022. The study compared the changes in platelet counts before and after the operation, and investigated the risk factors for thrombocytopenia following PDA closure in different groups and layers. RESULTS: The platelet count of patients with PDA significantly decreased after undergoing transcatheter PDA occlusion. Logistic regression analysis revealed that factors such as PDA diameter, occluder diameter, pressure difference on the two sides of the occluder, and residual shunt were associated with an increased risk of thrombocytopenia following PDA occlusion. Specifically, the size of the occluder and the pressure difference between the two sides of the occluder were found to have a negative correlation with the postoperative platelet count. Further subgroup analysis demonstrated that the incidence of total thrombocytopenia was significantly higher in the large PDA group compared to the small-medium PDA groups. CONCLUSION: Our findings suggest that occluder diameter, the pressure difference between the two sides of the occluder, and the residual shunt are major risk factors correlated with the incidence of postoperative thrombocytopenia. However, a multicenter and long-term prospective study is required to further evaluate the prognosis of PDA patients with thrombocytopenia after transcatheter occlusion.

[Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis].

OBJECTIVE: To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH). METHODS: Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score. RESULTS: Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(ß=-6.198, P=0.001) and femoral head collapse depth(ß=-4.085, P=0.014) had a significant negative impact on Harris hip score. CONCLUSION: Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Intracellular Nitroreductase-Triggered "On" and "Enhanced" Photoacoustic Signals for Sensitive Imaging of Tumor Hypoxia.

Current molecular photoacoustic (PA) probes are designed with either stimulus-turned "on" or assembly-enhanced signals to trace biological analytes/events. PA probes based on the nature-derived click reaction between 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) (i.e., CBT-Cys click reaction) possess both "turn-on" and "enhanced" PA signals; and thus, should have higher sensitivity. Nevertheless, such PA probes, particularly those for sensitive imaging of tumor hypoxia, remain scarce. Herein, a PA probe NI-Cys(StBu)-Dap(IR780)-CBT (NI-C-CBT) is rationally designed, which after being internalized by hypoxic tumor cells, is cleaved by nitroreductase under the reduction condition to yield cyclic dimer C-CBT-Dimer to turn the PA signal "ON" and subsequently assembled into nanoparticles C-CBT-NPs with additionally enhanced PA signal ("Enhanced"). NI-C-CBT exhibits 1.7-fold "ON" and 3.2-fold overall "Enhanced" PA signals in vitro. Moreover, it provides 1.9-fold and 2.8-fold overall enhanced PA signals for tumor hypoxia imaging in HeLa cells and HeLa tumor-bearing mice, respectively. This strategy is expected to be widely applied to design more "smart" PA probes for sensitive imaging of important biological events in vivo in near future.

Ketogenic diet inhibits neointimal hyperplasia by suppressing oxidative stress and inflammation.

OBJECTIVE: Neointimal hyperplasia is the primary mechanism underlying atherosclerosis and restenosis after percutaneous coronary intervention. Ketogenic diet (KD) exerts beneficial effects in various diseases, but whether it could serve as non-drug therapy for neointimal hyperplasia remains unknown. This study aimed to investigate the effect of KD on neointimal hyperplasia and the potential mechanisms. METHODS AND RESULTS: Carotid artery balloon-injury model was employed in adult Sprague-Dawley rats to induce neointimal hyperplasia. Then, animals were subjected to either standard rodent chow or KD. For in-vitro experiment, impacts of ß-hydroxybutyrate (ß-HB), the main mediator of KD effects, on platelet-derived growth factor BB (PDGF-BB) induced vascular smooth muscle cell (VSMC) migration and proliferation were determined. Balloon injury induced event intimal hyperplasia and upregulation of protein expression of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA), and these changes were significantly ameliorated by KD. In addition, ß-HB could markedly inhibit PDGF-BB induced VMSC migration and proliferation, as well as inhibiting expressions of PCNA and α-SMC. Furthermore, KD inhibited balloon-injury induced oxidative stress in carotid artery, indicated by reduced ROS level, malondialdehyde (MDA) and myeloperoxidase (MPO) activities, and increased superoxide dismutase (SOD) activity. We also found balloon-injury induced inflammation in carotid artery was suppressed by KD, indicated by decreased expressions of proinflammatory cytokines IL-1ß and TNF-α, and increased expression of anti-inflammatory cytokine IL-10. CONCLUSION: KD attenuates neointimal hyperplasia through suppressing oxidative stress and inflammation to inhibit VSMC proliferation and migration. KD may represent a promising non-drug therapy for neointimal hyperplasia associated diseases.

Transcatheter arterial chemoembolization plus apatinib with or without camrelizumab for unresectable hepatocellular carcinoma: a multicenter retrospective cohort study.

BACKGROUND: The evidence of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitor and immune checkpoint inhibitor in unresectable hepatocellular carcinoma (HCC) was limited. This study aimed to evaluate the role of TACE plus apatinib (TACE + A) and TACE combined with apatinib plus camrelizumab (TACE + AC) in patients with unresectable HCC. METHODS: This study retrospectively reviewed patients with unresectable HCC who received TACE + A or TACE + AC in 20 centers of China from January 1, 2019 to June 31, 2021. Propensity score matching (PSM) at 1:1 was performed to reduce bias. Treatment-related adverse events (TRAEs), overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were collected. RESULTS: A total of 960 eligible patients with HCC were included in the final analysis. After PSM, there were 449 patients in each group, and the baseline characteristics were balanced between two groups. At data cutoff, the median follow-up time was 16.3 (range: 11.9-21.4) months. After PSM, the TACE + AC group showed longer median OS (24.5 vs 18.0 months, p < 0.001) and PFS (10.8 vs 7.7 months, p < 0.001) than the TACE + A group; the ORR (49.9% vs 42.5%, p = 0.002) and DCR (88.4% vs 84.0%, p = 0.003) of the TACE + AC group were also higher than those in the TACE + A group. Fever, pain, hypertension and hand-foot syndrome were the more common TRAEs in two groups. CONCLUSIONS: Both TACE plus apatinib and TACE combined with apatinib plus camrelizumab were feasible in patients with unresectable HCC, with manageable safety profiles. Moreover, TACE combined with apatinib plus camrelizumab showed additional benefit.

A Cascade-Targeted Enzyme-Instructed Peptide Self-Assembly Strategy for Cancer Immunotherapy through Boosting Immunogenic Cell Death.

Immunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug-loaded, cascade-targeted, and enzyme-instructed self-assembling peptide nanomedicine (Comp. 4) for ICD-based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD-L1) binding peptide sequence (NTYYEDQG) and a mitochondria-specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a -GD FD FpD Y- assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD-L1. Moreover, the presence of PD-L1- and mitochondria-specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD-based antitumor immunity.

Exploration and identification of anoikis-related genes in polycythemia vera.

Background: Polycythemia Vera (PV) is a type of typical Myeloproliferative Neoplasms (MPNs) characterized with excessive erythropoiesis and thrombosis. Anoikis is a special programmed cell death mode induced by the adhesion disorder between cells and extracellular matrix (ECM) or adjacent cells facilitating cancer metastasis. However, few studies have focused on the role of anoikis in PV, especially on the development of PV. Methods: The microarray and RNA-seq results were screened from the Gene Expression Omnibus (GEO) database and the anoikis-related genes (ARGs) were downloaded from Genecards. The functional enrichment analysis of intersecting differentially expressed genes (DEGs) and protein-protein interaction (PPI) network analysis were performed to discover hub genes. The hub genes expression was tested in the training (GSE136335) and validation cohort (GSE145802), and RT-qPCR was performed to verify the gene expression in PV mice. Results: In the training GSE136335, a total of 1,195 DEGs was obtained from Myeloproliferative Neoplasm (MPN) patients compared with controls, among which 58 were anoikis-related DEGs. The significant enrichment of the apoptosis and cell adhesion pathways (i.e., cadherin binding) were shown in functional enrichment analysis. The PPI network was conducted to identify top five hub genes (CASP3, CYCS, HIF1A, IL1B, MCL1). The expression of CASP3 and IL1B were significantly upregulated both in validation cohort and PV mice and downregulated after treatment, suggesting that CASP3 and IL1B could be important indicators for disease surveillance. Conclusion: Our research revealed a relationship between anoikis and PV for the first time by combined analysis of gene level, protein interaction and functional enrichment, allowing novel insights into mechanisms of PV. Moreover, CASP3 and IL1B may become promising indicators of PV development and treatment.

Enzyme-Instructed Peptide Assembly Favored by Preorganization for Cancer Cell Membrane Engineering.

Innovative methods for engineering cancer cell membranes promise to manipulate cell-cell interactions and boost cell-based cancer therapeutics. Here, we illustrate an in situ approach to selectively modify cancer cell membranes by employing an enzyme-instructed peptide self-assembly (EISA) strategy. Using three phosphopeptides (pY1, pY2, and pY3) targeting the membrane-bound epidermal growth factor receptor (EGFR) and differing in just one phosphorylated tyrosine, we reveal that site-specific phosphorylation patterns in pY1, pY2, and pY3 can distinctly command their preorganization levels, self-assembling kinetics, and spatial distributions of the resultant peptide assemblies in cellulo. Overall, pY1 is the most capable of producing preorganized assemblies and shows the fastest dephosphorylation reaction in the presence of alkaline phosphatase (ALP), as well as the highest binding affinity for EGFR after dephosphorylation. Consequently, pY1 exhibits the greatest capacity to construct stable peptide assemblies on cancer cell membranes with the assistance of both ALP and EGFR. We further use peptide-protein and peptide-peptide co-assembly strategies to apply two types of antigens, namely ovalbumin (OVA) protein and dinitrophenyl (DNP) hapten respectively, on cancer cell membranes. This study demonstrates a very useful technique for the in situ construction of membrane-bound peptide assemblies around cancer cells and implies a versatile strategy to artificially enrich cancer cell membrane components for potential cancer immunotherapy.

Thyroid-Stimulating Hormone Levels within the Trimester-Specific Reference Intervals Are Correlated with Non-High-Density Lipoprotein Cholesterol and Remnant Cholesterol Concentrations in Pregnant Women.

OBJECTIVE: Thyroid-stimulating hormone (TSH) levels are associated with serum lipid concentrations in the general nonpregnant population. Here, we aimed to establish trimester-specific reference intervals and to explore the associations of their variations within the specific reference intervals during pregnancy. METHODS: Trimester-specific reference intervals were established according to the Clinical and Laboratory Standard Institute EP28-A3c guidelines using a direct sampling method based on a large prospective cohort. After making one-to-one matches, correlation analyses between TSH and lipid index levels, especially within the reference intervals, were conducted. RESULT: A total of 1648 pregnant women for TSH and 2045 subjects for lipids were recruited to establish the trimester-specific reference intervals. The upper reference limit (90% confidence interval) of TSH for pregnant women in the first trimester is 3.95 (3.66-4.29) mIU/L, which is very close to the default value (4.0 mIU/L) recommended by the American Thyroid Association in 2017. Apart from triglyceride and high-density lipoprotein cholesterol, TSH levels were positively associated with the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), and remnant cholesterol (RC) either in the entire range or within the specific reference intervals. Of note, the positive correlations between TSH and non-HDL-C and RC were, albeit similarly weak (r < 0.25), relatively more robust (P < .001). CONCLUSION: In this study, we showed positive correlations between TSH and lipid components within trimester-specific reference intervals, highlighting the need for the integrated management of pregnant women over age 35 and with nonoptimal lipid status in China.

Identification and validation of key immune-related genes with promising diagnostic and predictive value in systemic sclerosis.

AIMS: To screen and confirm key immune-related genes (IRGs) with diagnostic and predictive value in systemic sclerosis (SSc) and provide potential therapeutic targets for patients with SSc. MATERIALS AND METHODS: In Gene Expression Omnibus database (GEO), four datasets of gene expression profiling related to SSc were downloaded and used for the analysis in this study. After differential analysis of SSc cases and controls in GSE130955, the differentially expressed genes (DEGs) were overlapped with IRGs to obtain the immune-related differentially expressed genes (IR-DEGs) in SSc. In addition, functional annotation and pathway enrichment of IR-DEGs were conducted. The protein-protein interaction network (PPI) was constructed to identify key IR-DEGs. Using GSE58095, GSE181549 and GSE130953, the diagnostic and predictive abilities for the key IR-DEGs in SSc were validated. Finally, the screened key genes were confirmed in skin derived bleomycin (BLM)-induced SSc mice by Real-time PCR. KEY FINDINGS: NGFR, TNFSF13B, FCER1G, GIMAP5, TYROBP and CSF1R may have important or very high diagnostic value for SSc. TYROBP and TNFSF13B had moderate and mild predictive value respectively in SSc patients after treatment. Real-time PCR assay further confirmed that the expressions of Ngfr, Tyrobp, Csf1r, Fcer1g and Gimap5 were significantly higher in skin of BLM-induced SSc mice than that in controls. SIGNIFICANCE: The key IR-DEGs, including NGFR, TNFSF13B, TYROBP, CSF1R, FCER1G and GIMAP5, may become auxiliary diagnostic indicators and potential biomarkers for SSc. Moreover, TNFSF13B and TYROBP could have good prospects as predictive indicators in SSc patients that accepted cyclophosphamide or transplantation therapy.

Screening of potential hub genes involved in Cutaneous Leishmaniasis infection via bioinformatics analysis.

BACKGROUND: Cutaneous Leishmaniasis (CL) is the most common clinical form of leishmaniasis. Despite its low mortality, CL deserves further attention because its pathogenesis is currently no well-known or well-researched. METHODS: We downloaded the gene expression datasets of GSE55664 and GSE63931 with respect to leishmaniasis from the Gene Expression Synthesis (GEO) database. Additionally, the differentially expressed genes (DEGs) in the infection and control groups were identified by packages of R software. The Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway were utilized for the biological functional analysis. Subsequently, we identified the top ten hub genes from protein-protein interaction (PPI) networks based on STRING and Cytoscape software. The hub genes were validated in GraphPad Prism 8.0 using the GSE162760 dataset. Further, CIBERSORT was used to evaluate the immune cell infiltration proportions between the CL infection samples and the control samples based on the GSE43880 and GSE55664 datasets. RESULTS: The enrichment analysis revealed that DEGs were significantly involved in cell-mediated immune responses, such as leukocyte cell-cell adhesion and T-cell activation. STAT1, CCR7, CCR2, and CXCL10 were identified as hub genes with statistical significance. These hub genes showed close correlations with various immune cells, such as M1 cells and CD4-activated memory T-cells. CONCLUSIONS: In our research, we used bioinformatics analysis to identify some molecular biomarkers and significant pathways in CL infection. These hub genes may provide new options for future diagnosis and treatment.

Impact of paternal body mass index on assisted reproduction treatment outcomes: An updated systematic review and meta-analysis.

AIM: The aim was to provide updated evidence on the association of male body mass index (BMI) with outcomes of assisted reproduction technology (ART). METHODS: PubMed, Embase, and Scopus databases were systematically searched. The review included observational studies in patients undergoing ART, that is, either in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and compared rate of clinical pregnancy and live birth based on different categories of male BMI. Quality of the pooled findings was assessed using the GRADE criteria. RESULTS: A total of 19 studies were included in the review. Among subjects undergoing IVF, there were no significant differences in the rates of clinical pregnancy among overweight (odds ratio [OR] 1.38, 95% confidence interval [CI]: 0.65, 2.96) and obese (OR 1.86, 95% CI: 0.75, 4.58) BMI, compared to normal male BMI. Similarly, there were no significant differences in the rates of live birth among overweight (OR 1.04, 95% CI: 0.97, 1.13) and obese BMI (OR 0.90, 95% CI: 0.69, 1.18) when compared to males with normal BMI. Further, among those undergoing ICSI, there were no significant differences in the odds of clinical pregnancy among overweight (OR 0.98, 95% CI: 0.73, 1.33) and obese (OR 0.89, 95% CI: 0.62, 1.29). The odds of live births among overweight (OR 0.97, 95% CI: 0.89, 1.05) and obese (OR 0.95, 95% CI: 0.84, 1.07) male BMI were statistically similar to males with normal BMI undergoing ICSI. CONCLUSIONS: The low to very low-quality findings suggest no significant association of overweight and obese BMI with clinical pregnancy and live birth rates among couples undergoing either IVF or ICSI.

Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death.

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

Evaluation of the Effects on Uninfected Pregnant Women and Their Pregnancy Outcomes During the COVID-19 Pandemic in Beijing, China.

Background: People's lifestyles may have changed during the COVID-19 pandemic, which may have a profound impact on pregnant women and newborns. This study aims to assess the effects of the COVID-19 pandemic on uninfected pregnant women and their newborns, including potential environmental factors. Methods: We retrospectively analyzed the pregnancy complications of 802 cases in the pandemic group and 802 controls in the pre-pandemic group in a matched nested case-control study, and evaluated the association with sociodemographic features, lifestyles, and other factors in 311 pregnant women with adverse pregnancy outcomes. Results: Compared to the pre-pandemic group, the rates of anemia, vaginitis, shoulder dystocia, and adverse pregnancy outcomes such as preterm birth were increased in the pandemic group. After controlling for the covariates, we observed a higher risk of adverse pregnancy outcomes in the pandemic group. Pregnant women with adverse pregnancy outcomes had an increased rate of anemia and vaginal candidiasis. Conclusion: COVID-19 pandemic has profound effects on adverse pregnancy outcomes, suggesting the importance of ensuring regular prenatal checkups and keeping a healthy lifestyle.

Identification of differentially expressed genes and signaling pathways with Candida infection by bioinformatics analysis.

BACKGROUND: Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality. METHODS: In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis. RESULTS: A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein-protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were  significant statistical significance. CONCLUSIONS: In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection.

Identification of the Hub Genes and the Signaling Pathways in Human iPSC-Cardiomyocytes Infected by SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.