Spatiotemporal formation of the large vacuole regulated by the BIN2-VLG module is required for female gametophyte development in Arabidopsis.

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here, we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

Comparison of immune-related gene signatures and immune infiltration features in early- and late-onset preeclampsia.

BACKGROUND: Preeclampsia, a severe pregnancy syndrome, is widely accepted divided into early- and late-onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune-related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune-related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis. METHODS: The gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune-related genes set screened differentially expressed immune-related genes. Protein-protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real-time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single-sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes-miRNA network was performed by the NetworkAnalyst online tool. RESULTS: Immune score and stromal score were all lower in EOPE samples. The immune system-related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune-related genes (IL15, GZMB, IL1B and CXCL12) were identified based on a protein-protein interaction network and random forest. Quantitative real-time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine-cytokine receptor, para-inflammation, major histocompatibility complex class I and T cell co-stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes-miRNA regulatory network, revealing the correlation between hub genes and hsa-miR-374a-5p, hsa-miR-203a-3p, hsa-miR-128-3p, hsa-miR-155-3p, hsa-miR-129-2-3p and hsa-miR-7-5p. CONCLUSIONS: The innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune-related genes (IL15, GZMB, IL1B and CXCL12) were closely correlated with immune-related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE.

Kynurenine in IDO1high cancer cell-derived extracellular vesicles promotes angiogenesis by inducing endothelial mitophagy in ovarian cancer.

BACKGROUND: Mitophagy, a prominent cellular homeostasis process, has been implicated in modulating endothelial cell function. Emerging evidence suggests that extracellular vesicles (EVs) participate in intercellular communication, which could modulate tumor angiogenesis, a hallmark of ovarian cancer (OC) progression. However, the underlying mechanisms through how EVs regulate endothelial mitophagy associated with tumor angiogenesis during OC development remain obscure. METHODS: The effect of cancer cell-derived EVs on endothelial mitophagy and its correlation with tumor angiogenesis and OC development were explored by in vitro and in vivo experiments. Multi-omics integration analysis was employed to identify potential regulatory mechanisms of cancer cell-derived EVs on endothelial mitophagy, which is involved in tumor angiogenesis associated with OC development. These insights were then further corroborated through additional experiments. An orthotopic OC mouse model was constructed to assess the antiangiogenic and therapeutic potential of the Indoleamine 2,3 dioxygenase-1 (IDO1) inhibitor. RESULTS: Cancer cell-derived EVs promoted tumor angiogenesis via the activation of endothelial mitophagy, contributing to the growth and metastasis of OC. The aberrantly high expression of IDO1 mediated abnormal tryptophan metabolism in cancer cells and promoted the secretion of L-kynurenine (L-kyn)-enriched EVs, with associated high levels of L-kyn in EVs isolated from both the tumor tissues and patient plasma in OC. EVs derived from IDO1high ovarian cancer cells elevated nicotinamide adenine dinucleotide (NAD +) levels in endothelial cells via delivering L-kyn. Besides, IDO1high ovarian cancer cell-derived EVs upregulated sirt3 expression in endothelial cells by increasing acetylation modification. These findings are crucial for promoting endothelial mitophagy correlated with tumor angiogenesis. Notably, both endothelial mitophagy and tumor angiogenesis could be suppressed by the IDO1 inhibitor in the orthotopic OC mouse model. CONCLUSIONS: Together, our findings unveil a mechanism of mitophagy in OC angiogenesis and indicate the clinical relevance of EV enriched L-kyn as a potential biomarker for tumorigenesis and progression. Additionally, IDO1 inhibitors might become an alternative option for OC adjuvant therapy.

Ophthalmic Artery Morphology and Hemodynamics Associated with White Matter Hyperintensity.

Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.

CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. METHODS: TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays. RESULTS: A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11. CONCLUSIONS: Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate.

Negative life events and aggression among Chinese rural left-behind adolescents: do self-esteem and resilience mediate the relationship?

BACKGROUND: Left-behind adolescents (LBAs) are adolescents aged 11-18 years who are separated from their parents and left behind in local cities by one or both parents for a period of more than 6 months. LBAs in rural areas are likely to engage in aggressive behavior, which can affect interpersonal relationships, reduce academic performance, and even lead to anxiety and depression. To our knowledge, no studies have examined the mediating effect of resilience and self-esteem on the relationship between negative life events and aggression among Chinese rural LBAs. Therefore, this study aimed to explore the relationship between negative life events and aggression among Chinese rural LBAs and how self-esteem and resilience mediate the association. METHODS: Using a stratified random sampling method, 1344 LBAs in Hunan Province of China were investigated. Information was collected by a self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale and Aggression Scales to assess the psychology of LBAs. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. RESULTS: Negative life events were significantly related to self-esteem (r = - 0.338), resilience (r = - 0.359), and aggression (r = 0.441). Aggression was directly affected by self-esteem (ß = - 0.44) and resilience (ß = - 0.34). Negative life events were not only directly related to aggression (ß = 0.34, 95% CI: 0.275 ~ 0.398) but also showed an indirect effect on aggression through self-esteem and resilience. The direct effect, total effect and indirect effect of negative life events on aggression through self-esteem and resilience were 0.3364, 0.4344 and 0.0980, respectively. The mediating effect of self-esteem and resilience accounted for 22.56% of the relationship between negative life events and aggression. CONCLUSIONS: We found that self-esteem and resilience mediated most negative life events on aggression. It is imperative for educators and families to improve LBAs' self-esteem and resilience to reduce the occurrence of aggression. Future intervention studies should be designed to strengthen self-esteem and resilience.

Dual antibody-aided mesoporous nanoreactor for H2O2 self-supplying chemodynamic therapy and checkpoint blockade immunotherapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents a formidable challenge due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, rendering it unresponsive to conventional hormonal and targeted therapies. This study introduces the development of mesoporous nanoreactors (NRs), specifically mPDA@CuO2 NRs, as acid-triggered agents capable of self-supplying H2O2 for chemodynamic therapy (CDT). To enhance therapeutic efficacy, these NRs were further modified with immune checkpoint antagonists, specifically anti-PD-L1 and anti-CD24 antibodies, resulting in the formation of dual antibody-aided mesoporous nanoreactors (dAbPD-L1/CD24-mPDA@CuO2 NRs). These NRs were designed to combine CDT and checkpoint blockade immunotherapy (CBIT) for precise targeting of 4T1 TNBC cells. Remarkably, dAbPD-L1/CD24-mPDA@CuO2 NRs exhibited tumor-targeted CDT triggered by H2O2 and successfully activated immune cells including T cells and macrophages. This integrated approach led to a remarkable inhibition of tumor growth by leveraging the collaborative effects of the therapies. The findings of this study introduce a novel and promising strategy for the integrative and collaborative treatment of refractory cancers, providing valuable insights into addressing the challenges posed by aggressive breast cancer, particularly TNBC.

The application of new complex indicators in the detection of urine.

BACKGROUND: Accurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases. METHODS: All patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups (hematuria-dominant renal histologic lesions and non-hematuria-dominant renal histologic lesions) based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information. RESULTS: A total of 1,066 cases (678 hematuria-dominant renal histologic lesions) were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of "The ratio of the random URBC to 24-h albumin excretion" was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744] (95% Confidence interval (CI) 0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2 (3.81, 95% CI 2.66 ~ 5.50) to Q4 (14.17, 95% CI 9.09 ~ 22.72). The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856-0.905). CONCLUSION: The new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Morphologic Changes of the Temporomandibular Joint in Pruzansky-Kaban Type IIa Hemifacial Microsomia Postmandibular Distraction Osteogenesis.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is a powerful tool for the correction of hemifacial microsomia (HFM). The temporomandibular joint (TMJ) is the focus of attention in the diagnosis and treatment of HFM. This observational retrospective cross-sectional study aimed to investigate morphologic changes in TMJ post-MDO in type IIa HFM. METHODS: We recruited 48 patients with unilateral type IIa HFM who had completed MDO and mandibular distractor extraction (MDE). Data relating to the length, distance, angle, and volume of the TMJ were measured on 3-dimension models created by the analysis of computed tomography data. Normality analysis was performed by using the Shapiro-Wilk test. Data were compared with the paired t test and Wilcoxon signed-ranks test. RESULTS: The spaces between the affected condyle and the affected glenoid fossa before MDO were all significantly larger than before MDE (P<0.05). The breadth of the affected glenoid fossa before MDO was significantly longer than before MDE (P<0.001). The height of the affected condyle before MDO was significantly longer than before MDE (P<0.001). The volume of the affected condyle before MDO was significantly larger than before MDE (P<0.001). The ratio between the volume of the affected condyle and unaffected condyle before MDO was 0.20±0.13. The ratio between the volume of the affected condyle before MDE and MDO was 0.65±0.32. The resorption rate of the affected condyle post-MDO was 0.35±0.32. CONCLUSION: Herein, we characterized anatomic changes of the TMJ in type- IIa HFM post-MDO. Condylar resorption and the compression of space between the condyle and the glenoid fossa on the affected side were 2 typical manifestations. Our findings enhanced the understanding of the application of MDO on HFM.

A Novel Method for one-Stage Repair of the lip Vermilion Defects in Progressive Hemifacial Atrophy.

BACKGROUND: Progressive hemifacial atrophy often causes lip vermilion defects in patients. In this study, we described a one-stage repair method for lip defects in progressive hemifacial atrophy using a lip vermilion mucosal flap or combined dermal fat flap graft. PATIENTS AND METHODS: Patients diagnosed with progressive hemifacial atrophy with lip vermilion defects from 2010 to 2022 were included in this study. Based on the severity and location of the patient's lip defect, a lip vermilion mucosal flap was designed and transferred to the lip defect or combined with a hip dermal fat flap for one-stage repair of the lip morphology. Lip morphology and function of patients were followed up after surgery. RESULTS: A total of 22 patients were enrolled in this study, including 15 patients with lip defects on the upper lip alone and 7 patients with both upper and lower lip defects. Follow-up six months to two years postoperatively, all patients recovered uneventfully without complications. The repaired lips of the patient had a full and symmetrical morphology with no visible scarring. Two patients experienced transient dysesthesia of the lips postoperatively and both returned to normal after three months. All patients had good lip closure with normal dietary and speech function. CONCLUSIONS: The method we described for repairing lip defects in progressive hemifacial atrophy can achieve satisfactory aesthetic and functional lip results. The distinct advantage of this approach is that the patients undergo only one-stage operation and it can be used to repair both upper and lower lip defects.

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OBJECTIVES: To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration. METHODS: A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment. RESULTS: After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05). CONCLUSIONS: A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.

Highly sensitive fluorescent detection of EDIL3 overexpressed exosomes for the diagnosis of triple-negative breast cancer.

EDIL3 is a strong and highly accurate diagnostic marker for breast cancer, meanwhile, EDIL3 overexpressed exosomes are novel biomarkers for the early diagnosis of triple-negative breast cancer (TNBC). Here, we proposed a fluorescent detection method for EDIL3 overexpressed exosomes, which is simple and sensitive. Basically, we utilized a magnetic nanospheres (MNS) based liquid sandwich immunoassay strategy. MNS were modified with CD63 aptamers, which can immunologically bound to the CD63 protein on the surface of exosomes. Alexa Fluor 647 labeled anti-EDIL3 antibodies (Anti-EDIL3/AF647) were used as the fluorescent probes to recognize the EDIL3 on exosomes derived from a TNBC cell line (MDA-MB-231). With the target TNBC exosomes present, sandwich structures containing MNS, exosomes and fluorescent probes were formed. After magnetic purification, optical super resolution imaging of the products was conducted to check the specificity of the assay. In addition, fluorescence signals of the products were detected to quantitatively analyze the EDIL3 overexpressed exosomes. The linear range was found to be 7.78 × 101to 7.78× 106particlesµl-1. The detection limit was approximately 10 particlesµl-1. The feasibility of the method for the detection of exosomes in complex biological samples was also demonstrated. Such a simple and sensitive detection method for EDIL3 overexpressed exosomes holds a great potential in clinical diagnosis of TNBC.

Derivatives of sarcodonin A isolated from Sarcodon scabrosus reversed LPS-induced M1 polarization in microglia through MAPK/NF-κB pathway.

Emerging evidence suggests the regulation of microglial phenotype balance between M1 and M2 will be a potential therapeutic strategy for microglia-mediated neuroinflammation in Alzheimer's disease (AD). Herein, we evaluated the anti-neuroinflammatory effects and the underlying mechanism of a natural cyathane diterpenoid sarcodonin A (1) derived from the mushroom Sarcodon scabrosus and its six new derivatives (2-7). Lipopolysaccharide (LPS)-activated primary microglia and microglia cell lines were used as models. The nitrite test and immunostaining showed that the derivative named 6 was more effective in inhibiting neuroinflammation. qRT-PCR, ELISA, and western blotting revealed that 6 showed more significant suppression on mRNA and protein expression of proinflammatory M1 markers of TNF-α, IL-6, IL-1ß, iNOS, and COX-2, while more obvious potentiation on mRNA and protein levels of anti-inflammatory M2 markers of IL-10 and ARG-1. In mechanism, western blotting demonstrated that 6 inhibited LPS-induced activation of MAPK, and prevented LPS-stimulated nuclear translocation of NF-κB p65. Molecular docking revealed that 1 and 6 constructed interactions with iNOS. Collectively, the present study indicated that 1 and 6 might support neuroprotection by reversing LPS-induced microglia M1 polarization, implying that sarcodonin A can be a promising candidate for developing new therapeutics against AD by targeting microglia-mediated neuroinflammation.

Diagnostic accuracy of anthropometric indices for discriminating elevated blood pressure in pediatric population: a systematic review and a meta-analysis.

BACKGROUND: Childhood obesity is more likely to increase the chance of many adult health problems. Numerous studies have shown obese children to be more prone to elevated blood pressure (BP) and hypertension. It is important to identify an obesity anthropometric index with good discriminatory power for them in pediatric population. METHODS: MEDLINE/PubMed, Web of Science, and Cochrane databases were retrieved comprehensively for eligible studies on childhood obesity and hypertension/elevated BP through June 2021. The systematic review and meta-analysis of studies used receiver operating characteristics (ROC) curves for evaluating the discriminatory power of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in distinguishing children with elevated BP and hypertension. RESULTS: 21 cross-sectional studies involving 177,943 children and 3-19 years of age were included in our study. Meta-analysis showed that the pooled area under the reporting receiver-operating characteristic curves (AUC) and 95% confidence intervals (CIs) for BMI, WC, and WHtR to detect hypertension of boys were 0.68 (0.64, 0.72), 0.69 (0.64, 0.74), 0.67 (0.63, 0.71), for elevated BP, the pooled AUCs and 95% CIs were 0.67 (0.61, 0.73), 0.65 (0.58, 0.73), 0.65 (0.61, 0.71). The pooled AUCs and 95% CIs for BMI, WC and WHtR of predicting hypertension were 0.70 (0.66, 0.75), 0.69 (0.64, 0.75), 0.67 (0.63, 0.72) in girls, the pooled AUCs and 95% CIs of predicting elevated BP were 0.63 (0.61, 0.65), 0.62 (0.60, 0.65), 0.62 (0.60, 0.64) respectively. There was no anthropometric index was statistically superior in identifying hypertension and elevated BP, however, the accuracy of BMI predicting hypertension was significantly higher than elevated BP in girls (P < 0.05). The subgroup analysis for the comparison of BMI, WC and WHtR was performed, no significant difference in predicting hypertension and elevated BP in pediatric population. CONCLUSIONS: This systematic review showed that no anthropometric index was superior in identifying hypertension and elevated BP in pediatric population. While compared with predicting elevated BP, all the indicators showed superiority in predicting hypertension in children, the difference was especially obvious in girls. A better anthropometric index should be explored to predict children's early blood pressure abnormalities.

Recent advances in functional conservation and divergence of recombinase RAD51 and DMC1.

Meiosis is a specialized cell division that occurs in reproductive cells during sexual reproduction. It contains once DNA replication following nucleus division twice, thus producing haploid gametes. Fusion of male and female gametes restores genome to the diploid level, which not only ensures the genome stability between generations during sexual reproduction, but also leads to genetic diversity among offspring. Meiosis homologous recombination (HR) is one of the crucial events during meiotic prophase I, and it not only ensures the subsequently faithful segregation of homologous chromosomes (homologs), but also exchanges genetic information between homologs with greatly increasing the genetic diversity of progeny. RAD51 (RADiation sensitive 51) and DMC1 (disruption Meiotic cDNA 1) are essential recombinases for the HR process, and have certain commonalities and differences. In this review, we summarize and compare the conserved and differentiated features of RAD51 and DMC1 in terms of origin, evolution, structure, and function, we also provide an outlook on future research directions to further understand and study the molecular mechanisms in regulation of meiotic recombination.

Pristimerin protects against inflammation and metabolic disorder in mice through inhibition of NLRP3 inflammasome activation.

Excessive activation of NLRP3 inflammasome is associated with the pathogenesis of inflammatory diseases. Pristimerin (Pri) is a quinonoid triterpene derived from traditional Chinese medical herb Celastraceae and Hippocrateaceae. Pri has shown antifungal, antibacterial, antioxidant, and anticancer activities. In this study we investigated whether NLRP3 inflammasome was associated with the anti-inflammatory activity of Pri. We showed that Pri (0.1-0.4 µM) dose-dependently blocked caspase-1 activation and IL-1ß maturation in LPS-primed mouse bone-marrow-derived macrophages (BMDMs). Pri specifically inhibited NLRP3 inflammasome activation, had no visible effects on NLRC4 and AIM2 inflammasome activation. Furthermore, we demonstrated that Pri blocked the assembly of the NLRP3 inflammasome via disturbing the interaction between NEK7 and NLRP3; the α, ß-unsaturated carbonyl moiety of Pri was essential for NLRP3 inflammasome inactivation. In LPS-induced systemic inflammation mouse model and MSU-induced mouse peritonitis model, preinjection of Pri (500 µg/kg, ip) produced remarkable therapeutic effects via inhibition of NLRP3 inflammasome in vivo. In HFD-induced diabetic mouse model, administration of Pri (100 µg· kg-1 ·d-1, ip, for 6 weeks) reversed HFD-induced metabolic disorders via suppression of NLRP3 inflammasome activation. Taken together, our results demonstrate that Pri acts as a NLRP3 inhibitor, suggesting that Pri might be useful for the treatment of NLRP3-associated diseases.

10,11-dehydrocurvularin exerts antitumor effect against human breast cancer by suppressing STAT3 activation.

Aberrant activation of signal transducer and activator of transcription 3 (STAT3) plays a critical role in many types of cancers. As a result, STAT3 has been identified as a potential target for cancer therapy. In this study we identified 10,11-dehydrocurvularin (DCV), a natural-product macrolide derived from marine fungus, as a selective STAT3 inhibitor. We showed that DCV (2-8 µM) dose-dependently inhibited the proliferation, migration and invasion of human breast cancer cell lines MDA-MB-231 and MDA-MB-468, and induced cell apoptosis. In the two breast cancer cell lines, DCV selectively inhibited the phosphorylation of STAT3 Tyr-705, but did not affect the upstream components JAK1 and JAK2, as well as dephosphorylation of STAT3. Furthermore, DCV treatment strongly inhibited IFN-γ-induced STAT3 phosphorylation but had no significant effect on IFN-γ-induced STAT1 and STAT5 phosphorylation in the two breast cancer cell lines. We demonstrated that the α, ß-unsaturated carbonyl moiety of DCV was essential for STAT3 inactivation. Cellular thermal shift assay (CETSA) further revealed the direct engagement of DCV with STAT3. In nude mice bearing breast cancer cell line MDA-MB-231 xenografts, treatment with DCV (30 mg·kg-1·d-1, ip, for 14 days) markedly suppressed the tumor growth via inhibition of STAT3 activation without observed toxicity. Our results demonstrate that DCV acts as a selective STAT3 inhibitor for breast cancer intervention.

Shared paternal ancestry of Han, Tai-Kadai-speaking, and Austronesian-speaking populations as revealed by the high resolution phylogeny of O1a-M119 and distribution of its sub-lineages within China.

OBJECTIVES: The aim of this research was to explore the origin, diversification, and demographic history of O1a-M119 over the past 10,000 years, as well as its role during the formation of East Asian and Southeast Asian populations, particularly the Han, Tai-Kadai-speaking, and Austronesian-speaking populations. MATERIALS AND METHODS: Y-chromosome sequences (n = 141) of the O1a-M119 lineage, including 17 newly generated in this study, were used to reconstruct a revised phylogenetic tree with age estimates, and identify sub-lineages. The geographic distribution of 12 O1a-M119 sub-lineages was summarized, based on 7325 O1a-M119 individuals identified among 60,009 Chinese males. RESULTS: A revised phylogenetic tree, age estimation, and distribution maps indicated continuous expansion of haplogroup O1a-M119 over the past 10,000 years, and differences in demographic history across geographic regions. We propose several sub-lineages of O1a-M119 as founding paternal lineages of Han, Tai-Kadai-speaking, and Austronesian-speaking populations. The sharing of several young O1a-M119 sub-lineages with expansion times less than 6000 years between these three population groups supports a partial common ancestry for them in the Neolithic Age; however, the paternal genetic divergence pattern is much more complex than previous hypotheses based on ethnology, archeology, and linguistics. DISCUSSION: Our analyses contribute to a better understanding of the demographic history of O1a-M119 sub-lineages over the past 10,000 years during the emergence of Han, Austronesians, Tai-Kadai-speaking populations. The data described in this study will assist in understanding of the history of Han, Tai-Kadai-speaking, and Austronesian-speaking populations from ethnology, archeology, and linguistic perspectives in the future.

Galectin-1 expression in the serum and placenta of pregnant women with fetal growth restriction and its significance.

BACKGROUND: This study aims to investigate galectin-1 (Gal-1) expression in the serum and placenta of pregnant women with fetal growth restriction (FGR) and its significance. METHODS: Thirty-one pregnant women with single-birth FGR but without comorbidities, eight pregnant women with FGR and preeclampsia (PE), and eight pregnant women with FGR and gestational diabetes mellitus (GDM) were enrolled as the study group, while 20 pregnant women with normal singleton pregnancy in the same period were enrolled as the control group. The serum Gal-1 level was detected using an enzyme-linked immunosorbent assay (ELISA), and Gal-1 expression in the placenta was detected by western blot. RESULTS: The results revealed that, compared with the control group, the serum Gal-1 level decreased in the women with FGR without comorbidities, and the difference was statistically significant (P < 0.001). Compared with the control group, the difference in serum Gal-1 expression in the FGR-PE group was not statistically significant (P = 0.29). The peripheral serum Gal-1 level decreased in the FGR-GDM group compared with the control group, and the difference was statistically significant (P < 0.001). The serum Gal-1 level was positively correlated with birth weight (r2 = 0.172, P < 0.01). Compared with the control group, the Gal-1 expression level decreased in the placenta of the pregnant women with FGR without comorbidities (P < 0.05). CONCLUSIONS: Gal-1 exhibits low expression in the serum and placenta of pregnant women with FGR. In addition, Gal-1 may be involved in the pathogenesis of FGR and could represent a new diagnostic marker of the disease.