A Comprehensive Interaction Network Constructed Using miRNAs and mRNAs Provides New Insights into Potato Tuberization under High Temperatures.

High temperatures delay tuberization and decrease potato (Solanum tuberosum L.) yields. However, the molecular mechanisms and regulatory networks underlying tuberization under high temperatures remain largely unknown. Here, we performed the mRNA and miRNA sequencing of leaves and stems to identify genes and regulatory networks involved in tuberization under high temperatures. A total of 2804 and 5001 differentially expressed genes (DEGs) under high-temperature stress were identified in leaves and stems, respectively. These genes were significantly enriched in gene ontology terms regarding meristem development, the sucrose biosynthetic process, and response to heat. Meanwhile, 101 and 75 differentially expressed miRNAs (DEmiRNAs) were identified in leaves and stems, respectively. We constructed an interaction network between DEmiRNAs and DEGs, identifying 118 and 150 DEmiRNA-DEG pairs in leaves and stems, respectively. We found three miRNA-mRNA candidate modules involved in tuberization under high temperatures, including stu-miR8030-5p/StCPY714, stu-miR7981f-p5/StAGL8a, and stu-miR10532A/StAGL8b. Our study constructed an interaction network between miRNAs and target genes and proposes candidate miRNA-gene modules that regulate tuber formation under high temperatures. Our study provides new insights for revealing the regulatory mechanism of the high-temperature inhibition of tuberization and also provides gene resources for improving the heat tolerance in potatoes.

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage.

Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.

High serum total bilirubin as a potential protective factor for gestational diabetes mellitus: A retrospective cohort study of 92,885 Chinese pregnant women.

AIMS: Identifying physiological factors that could reduce pregnant women's risk for developing gestational diabetes mellitus (GDM) is crucial for early prevention and intervention. We aimed to examine whether higher serum levels of total bilirubin (TBIL) were associated with a decreased risk of GDM. METHODS: We conducted a retrospective cohort study in a tertiary care hospital in Shanghai, China. A total of 92,885 pregnant women were included. Serum TBIL levels were determined during the first antenatal visit before 24 weeks of gestation and GDM was diagnosed with a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. RESULTS: A total of 13,037 GDM cases were identified, a prevalence of 14.0 % (13,037/92,885). These women had a higher median TBIL concentration 7.9 versus 7.6 mmol/l (P < 0.001). For the 91,051 women with TBIL within the physiologically normal range (≤ 17.1 µmol/l), a one interquartile range increase in TBIL (3.4 µmol/l) was associated with a decreased risk of GDM: adjusted odds ratio (OR)=0.89 [95 % CI 0.87;0.92]. For these women, the adjusted ORs for GDM across TBIL quartiles were: 0.92 [0.88;0.97] for the second, 0.85 [0.81;0.90] for the third, and 0.78 [0.74;0.83] for the fourth quartile in comparison with the first quartile. CONCLUSION: Our study demonstrated that elevated serum TBIL levels were associated with decreased risk of GDM and supported its potential role in the prevention and early intervention of GDM.

Gestational diabetes mellitus and risk of long-term all-cause and cardiac mortality: a prospective cohort study.

BACKGROUND: To investigate the association between gestational diabetes mellitus (GDM) without subsequent overt diabetes and long-term all-cause and cardiac mortality. METHODS: This prospective cohort study included 10,327 women (weighted population: 132,332,187) with a pregnancy history from the National Health and Nutrition Examination Survey (2007 to 2018). Participants were divided into three groups (GDM alone, overt diabetes, and no diabetes). Mortality data was linked from the National Death Index up to December 31, 2019. Multivariable Cox regression analysis was performed to examine the association between GDM alone and overt diabetes with all-cause mortality and cardiac mortality. Data analysis was performed from October 2022 to April 2023. RESULTS: Among the participants, 510 (weighted 5.3%) had GDM alone and 1862 (weighted 14.1%) had overt diabetes. Over a median follow-up period of 6.7 years (69,063 person-years), there were 758 deaths. The GDM group did not show an increased risk of all-cause mortality (hazard ratio [HR] 0.67; 95% CI, 0.25-1.84), while the overt diabetes group had a significantly higher risk (HR 1.95; 95% CI, 1.62-2.35). Similarly, the GDM group did not exhibit an elevated risk of cardiac mortality (HR 1.48; 95% CI, 0.50-4.39), whereas the overt diabetes group had a significantly higher risk (HR 2.37; 95% CI, 1.69-3.32). Furthermore, sensitivity analysis focusing on women aged 50 or above showed that the HR of GDM history for all-cause mortality was 1.14 (95% CI, 0.33-3.95) and the HR for cardiac mortality was 1.74 (95% CI, 0.49-6.20). CONCLUSIONS: GDM alone was not associated with an increased risk of all-cause and cardiac mortality, while overt diabetes was significantly associated with both types of mortality.

A BET inhibitor, NHWD-870, can downregulate dendritic cells maturation via the IRF7-mediated signaling pathway to ameliorate imiquimod-induced psoriasis-like murine skin inflammation.

Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1ß, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

A molecularly engineered fully bio-derived phosphorylated furan-based flame retardant for biomass-based fabrics.

With the increasing awareness of environmental protection, the demand for eco-friendly bio-derived flame-retardant for textiles has received increasing attention. In this work, a fully bio-derived phosphorylated furan-based flame retardant (FAP) was synthesized by the Schiff reaction of furan-based compounds (furfural and furfurylamine). To evaluate the application scope and flame retardant efficiency of FAP, cotton fabrics and PLA nonwovens were selected as biomass-based representatives of natural fiber materials and synthetic fiber materials, respectively. Significantly, based on the composition of furan ring, phosphorus and nitrogen containing components of FAP, excellent charring and flame retardant properties of coated cotton fabrics and PLA nonwovens can be expected. TGA results showed that the residual char of C-FAP-3 and P-FAP-3 were 39.7% (increased by 267.6%) and 16.7% (increased by 215.1%), respectively, higher than those of control cotton (10.8%) and PLA nonwoven (5.3%). Cone test results exhibited that the peak heat release rate (PHRR) and total heat release (THR) values of C-FAP-3 were sharply decreased by 69.4% and 37.8%, respectively. P-FAP-3 also displayed a significant reduction in PHRR, implying high flame retardancy of C-FAP-3 and P-FAP-3. Notably, through the weight gains of FAP coating on cotton and PLA as well as the final LOI and VBT results of the flame retardant treated fabrics, it can be preliminarily inferred that control cotton fabrics are more likely to achieve better flame retardant effects than PLA. Additionally, the facile synthetic strategy of fully bio-derived flame retardants is expected to promote the development of green flame retardant strategies for high-performance textiles.

Novel LDLR variants affecting low density lipoprotein metabolism identified in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease of lipid metabolism mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Genetic detection of patients with FH help with precise diagnosis and treatment, thus reducing the risk of coronary heart disease (CHD) and other related diseases. The study aimed to identify the causative gene mutations in a Chinese FH family and reveal the pathogenicity and the mechanism of these mutations. METHODS AND RESULTS: Whole exome sequencing was performed in a patient with severe lipid metabolism dysfunction seeking fertility guidance from a Chinese FH family. Two LDLR variants c.1875 C > G (p.N625K; novel variant) and c.1448G > A (p.W483*) were identified in the family. Wildtype and mutant LDLR constructs were established by the site-direct mutagenesis technique. Functional studies were carried out by cell transfection to evaluate the impact of detected variants on LDLR activity. The two variants were proven to affect LDL uptake and binding, resulting in cholesterol clearance reduction to different degrees. According to The American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines, the W483* variant was classified as "Pathogenic", while the N625K variant as "VUS". CONCLUSIONS: Our results provide novel experimental evidence of functional alteration by LDLR variants identified in our study and expand the mutational spectrum of LDLR mutation induced FH.

Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes.

Aneuploidy seriously compromises female fertility and increases incidence of birth defects. Rates of aneuploidy in human eggs from even young women are significantly higher than those in other mammals. However, intrinsic genetic factors underlying this high incidence of aneuploidy in human eggs remain largely unknown. Here, we found that ectopic expression of human TUBB8 in mouse oocytes increases rates of aneuploidy by causing kinetochore-microtubule (K-MT) attachment defects. Stretched bivalents in mouse oocytes expressing TUBB8 are under less tension, resulting in continuous phosphorylation status of HEC1 by AURKB/C at late metaphase I that impairs the established correct K-MT attachments. This reduced tension in stretched bivalents likely correlates with decreased recruitment of KIF11 on meiotic spindles. We also found that ectopic expression of TUBB8 without its C-terminal tail decreases aneuploidy rates by reducing erroneous K-MT attachments. Importantly, variants in the C-terminal tail of TUBB8 were identified in patients with recurrent miscarriages. Ectopic expression of an identified TUBB8 variant in mouse oocytes also compromises K-MT attachments and increases aneuploidy rates. In conclusion, our study provides novel understanding for physiological mechanisms of aneuploidy in human eggs as well as for pathophysiological mechanisms involved in recurrent miscarriages.

Multifunctional Textiles with Flame Retardant and Antibacterial Properties: A Review.

It is well known that bacterial infections and fire-hazards are potentially injurious in daily life. With the increased security awareness of life and properties as well as the improvement of living standards, there has been an increasing demand for multifunctional textiles with flame retardant and antibacterial properties, especially in the fields of home furnishing and medical protection. So far, various treatment methods, including the spray method, the dip-coating method, and the pad-dry-cure method, have been used to apply functional finishing agents onto fabrics to achieve the functionalization in the past exploration stage. Moreover, in addition to the traditional finishing technology, a number of novel technologies have emerged, such as layer-by-layer (LBL) deposition, the sol-gel process, and chemical grafting modification. In addition, some natural biomasses, including chitin, chitosan (CS), and several synthetic functional compounds that possess both flame-retardant and bacteriostatic properties, have also received extensive attention. Hence, this review focuses on introducing some commonly used finishing technologies and flame retardant/antibacterial agents. At the same time, the advantages and disadvantages of different methods and materials were summarized, which will contribute to future research and promote the development and progress of the industry.

Corrigendum to 'Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.' [EClinicalMedicine 59 (2023) 101981].

[This corrects the article DOI: 10.1016/j.eclinm.2023.101981.].

Methodological evolution of potato yield prediction: a comprehensive review.

Timely and accurate prediction of crop yield is essential for increasing crop production, estimating planting insurance, and improving trade benefits. Potato (Solanum tuberosum L.) is a staple food in many parts of the world and improving its yield is necessary to ensure food security and promote related industries. We conducted a comprehensive literature survey to demonstrate methodological evolution of predicting potato yield. Publications on predicting potato yield based on methods of remote sensing (RS), crop growth model (CGM), and yield limiting factor (LF) were reviewed. RS, especially satellite-based RS, is crucial in potato yield prediction and decision support over large farm areas. In contrast, CGM are often utilized to optimize management measures and address climate change. Currently, combined with the advantages of low cost and easy operation, unmanned aerial vehicle (UAV) RS combined with artificial intelligence (AI) show superior potential for predicting potato yield in precision management of large-scale farms. However, studies on potato yield prediction are still limited in the number of varieties and field sample size. In the future, it is critical to employ time-series data from multiple sources for a wider range of varieties and large field sample sizes. This study aims to provide a comprehensive review of the progress in potato yield prediction studies and to provide a theoretical reference for related research on potato.

Association of inactivated COVID-19 vaccination with maternal coagulation function in early pregnancy.

Reports of rare but severe thrombotic events after receiving some COVID-19 vaccines brought concerns for the possibility of vaccine-induced coagulation abnormality. However, no study has reported the impacts of COVID-19 vaccination on coagulation function in pregnant women. We aimed to explore whether vaccination with inactivated COVID-19 vaccines before pregnancy was associated with coagulation changes in pregnant women. We conducted a retrospective cohort study in a tertiary-care hospital in Shanghai, China. A total of 5166 pregnant women were included, of whom 2721 (52.7%) completed vaccination before conception. Compared with unvaccinated women, the mean serum levels of prothrombin time (PT) and fibrinogen (FIB) were lower in vaccinated women by 0.09 (ß = -0.09, 95% confidence interval [CI], -0.13, -0.05) mg/L and 0.11 (ß = -0.11, 95% CI, -0.15, -0.07) mg/L, and the mean D-Dimer (D-D) levels were higher by 0.12 (ß = 0.12, 95% CI, 0.09, 0.15) mg/L. However, no significant association was observed between COVID-19 vaccination and serum levels of activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) or thrombin time (TT). Our findings suggested that inactivated COVID-19 vaccination before conception resulted in a small change in maternal coagulation function, but this might not have clinical significance.

Ultra-light-weight, anti-flammable and water-proof cellulosic aerogels for thermal insulation applications.

Cellulosic aerogels (CNF) are considered naturally available thermal insulating materials as substitutes for conventional polymeric aerogels owing to their extensive sources, low density, low thermal conductivity, sustainability and biodegradability. However, cellulosic aerogels suffer from high flammability and hygroscopicity. In this work, a novel P/N-containing flame retardant (TPMPAT) was synthesized to modify cellulosic aerogels to improve their anti-flammability. TPMPAT/CNF aerogels were further modified by polydimethylsiloxane (PDMS) to enhance the water-proof characteristics. Although the addition of TPMPAT and/or PDMS slightly increased the density and thermal conductivity of the composite aerogels, those values were still comparable to the commercial polymeric aerogels. Compared with pure CNF aerogel, the cellulose aerogel modified by TPMPAT and/or PDMS had higher T-10%, T-50% and Tmax, which indicated that the modified cellulose aerogels have better thermal stability. TPMPAT modification made CNF aerogels highly hydrophilic, while TPMPAT/CNF aerogel modified by PDMS became a highly hydrophobic material with a water contact angle (WCA) of 142°. Pure CNF aerogel burned rapidly after ignition, showing a low limiting oxygen index (LOI) of 23.0% and no UL-94 grade. In contrast, both TPMPAT/CNF-30% and PDMS-TPMPAT/CNF-30% showed self-extinction behaviors with a UL-94 V-0 grade, implying high fire resistance. Combined with high anti-flammability and hydrophobicity, the ultra-light-weight cellulosic aerogels show great potential for thermal insulation applications.

Application of "Internet+" cognitive-behavioral intervention in caregivers of children with congenital heart disease undergoing elective surgery during the COVID-19 pandemic.

OBJECTIVE: To explore the effects of cognitive and behavioral interventions for caregivers of children undergoing interventional surgery for congenital heart disease (CHD) during COVID-19. METHODS: A prospective study was conducted on 140 children with CHD who were hospitalized in the Department of Cardiology in a children's hospital from March 2020 to March 2022. The children were randomly divided into an intervention group and a control group, with 70 cases in each group. In the control group, caregivers gave routine care, and in the intervention group, "Internet+" cognitive and behavioral interventions were given. The psychological status of caregivers before and after intervention, day care ability on the operation day, readiness for hospital discharge of the caregivers, sleep quality, and postoperative complications of the children, the medication compliance, review compliance and satisfaction were compared between the two groups. RESULTS: During the COVID-19 pandemic, the anxiety and depression scores of caregivers in the intervention group were significantly lower than those in the control group (P<0.05), and the caregiving ability and readiness for hospital discharge of the caregivers in the intervention group were better than those in the control group (P<0.05). The sleep quality of children in the intervention group was significantly better than that in the control group during the first week after operation (P<0.05). Postoperative complications were significantly fewer in the intervention group than in the control group (χ 2=24.433, P<0.001). The medication compliance, review compliance, and satisfaction were higher in the intervention group than in the control group (P<0.05). CONCLUSION: During the pandemic period of COVID-19, "Internet+" cognitive and behavioral intervention has a good effect and should be promoted in clinical practice.

Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.

Background: As the COVID-19 pandemic continues to spread, the number of associated deaths continues to increase, especially among those with pre-existing conditions. Azvudine is recommended as a priority treatment for patients with COVID-19, but its efficacy in patients with pre-existing conditions is unknown. Methods: This is a single-centre, retrospective cohort study between December 5, 2022 and January 31, 2023 in Xiangya Hospital of Central South University in China to evaluate the clinical efficacy of Azvudine in hospitalised patients with COVID-19 and pre-existing conditions. Patients with Azvudine and controls were propensity score-matched (1:1) for age, gender, vaccination status, time from symptom onset to treatment exposure, severity at admission, concomitant treatments initiated at admission. The primary outcome was a composite outcome of disease progression, and the secondary outcome was each of these individual disease progression outcomes. The univariate Cox regression model was used to estimate a hazard ratio (HR) with 95% confidence interval (CI) for each result between the groups. Findings: We identified 2118 hospitalised patients with COVID-19 during the study period, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 245 Azvudine recipients and 245 matched controls. Azvudine recipients had lower crude incidence rate of composite disease progression outcome compared with matched controls (7.125/1000 person-days vs. 16.004/1000 person-days, P = 0.018). There was no significant difference in all-cause death between these two groups (1.934/1000 person-days vs. 4.128/1000 person-days, P = 0.159). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome compared with matched controls (HR: 0.49; 95% CI: 0.27-0.89, P = 0.016). A significant difference in all-cause death was not found (HR: 0.45; 95% CI: 0.15-1.36, P = 0.148). Interpretation: These findings indicate that Azvudine therapy showed substantial clinical benefits in hospitalised patients with COVID-19 and pre-existing conditions, and should be considered for this population of patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant Nos. 82103183 to F. Z., 82102803, 82272849 to G. D.), National Natural Science Foundation of Hunan Province (Grant Nos. 2022JJ40767 to F. Z., 2021JJ40976 to G. D.), Huxiang Youth Talent Program (Grant Nos. 2022RC1014 to M.S.) and Ministry of Industry and Information Technology of China (Grant Nos. TC210804V to M.S.).

Single-Cell Profiling Reveals Sustained Immune Infiltration, Surveillance, and Tumor Heterogeneity in Infiltrative Basal Cell Carcinoma.

Infiltrative basal cell carcinoma (iBCC) is a particularly aggressive subtype of basal cell carcinoma that tends to progress and recur after surgery, and its malignancy is closely related to the tumor microenvironment. In this study, we performed a comprehensive single-cell RNA analysis to profile 29,334 cells from iBCC and adjacent normal skin. We found active immune collaborations enriched in iBCC. Specifically, SPP1+CXCL9/10high macrophage 1 had strong BAFF signaling with plasma cells, and T follicular helper-like cells highly expressed the B-cell chemokine CXCL13. Heterogeneous proinflammatory SPP1+CXCL9/10high macrophage 1 and angiogenesis-related SPP1+CCL2high macrophage 1 were identified within the tumor microenvironment. Interestingly, we found an upregulation of major histocompatibility complex I molecules in fibroblasts in iBCC compared with those in adjacent normal skin. Moreover, MDK signals derived from malignant basal cells were markedly increased, and their expression was an independent factor in predicting the infiltration depth of iBCC, emphasizing its role in driving malignancy and remodeling the tumor microenvironment. In addition, we identified differentiation-associated SOSTDC1+IGFBP5+CTSV+ malignant basal subtype 1 and epithelial-mesenchymal transition-associated TNC+SFRP1+CHGA+ malignant basal subtype 2 cells. The high expression of malignant basal 2 cell markers was associated with the invasion and recurrence of iBCC. Altogether, our study helps to elucidate the cellular heterogeneity in iBCC and provides potential therapeutic targets for clinical research.

Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

No association of vaccination with inactivated COVID-19 vaccines before conception with pregnancy complications and adverse birth outcomes: A cohort study of 5457 Chinese pregnant women.

Data on the safety of inactivated COVID-19 vaccines in pregnant women is limited and monitoring pregnancy outcomes is required. We aimed to examine whether vaccination with inactivated COVID-19 vaccines before conception was associated with pregnancy complications or adverse birth outcomes. We conducted a birth cohort study in Shanghai, China. A total of 7000 healthy pregnant women were enrolled, of whom 5848 were followed up through delivery. Vaccine administration information was obtained from electronic vaccination records. Relative risks (RRs) of gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), preterm birth (PTB), low birth weight (LBW), and macrosomia associated with COVID-19 vaccination were estimated by multivariable-adjusted log-binomial analysis. After exclusion, 5457 participants were included in the final analysis, of whom 2668 (48.9%) received at least two doses of an inactivated vaccine before conception. Compared with unvaccinated women, there was no significant increase in the risks of GDM (RR = 0.80, 95% confidence interval [CI], 0.69, 0.93), HDP (RR = 0.88, 95% CI, 0.70, 1.11), or ICP (RR = 1.61, 95% CI, 0.95, 2.72) in vaccinated women. Similarly, vaccination was not significantly associated with any increased risks of PTB (RR = 0.84, 95% CI, 0.67, 1.04), LBW (RR = 0.85, 95% CI, 0.66, 1.11), or macrosomia (RR = 1.10, 95% CI, 0.86, 1.42). The observed associations remained in all sensitivity analyses. Our findings suggested that vaccination with inactivated COVID-19 vaccines was not significantly associated with an increased risk of pregnancy complications or adverse birth outcomes.

Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage.

Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.

NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes.

Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK'772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK'772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.