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Context: The causal association and biological mechanism linking serum 25-hydroxyvitamin D to stroke risk lacks epidemiological evidence., Objective: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors., Design: The community-based prospective community-based cohort study, the Chin-Shan Community Cardiovascular Cohort, was conducted from 1990 to December 2011, with external validation using a two-sample Mendelian randomization (MR) study., Patients: A total of 1,778 participants with serum 25-hydroxyvitamin D data were enrolled., Methods: In the CCCC observational study, the outcome was ascertained as stroke, while in the two-sample MR study, it was defined as ischemic stroke. Causal effects were estimated using restricted cubic spline analysis, COX proportional hazard ratios, mediation analysis, and two-sample MR., Results: Over 12 years (21,598 person-years) of follow-up, 163 participants (9.17%) developed stroke. Higher 25(OH)D concentrations were associated with lower stroke risk (hazard ratio: 0.64; 95% confidence interval, 0.43-0.96) after full-model adjustments. Mediation analysis showed a significant association between 25(OH)D concentration and stroke risk mediated by hypertension in unadjusted models (mediation percentage 23.3%, p=0.008) that became non-significant in full models (mediation percentage, 15.5%; p=0.072). Two-sample MR confirmed a significant inverse association between genetically determined 25(OH)D and stroke risk (IVW OR: 0.92; 95% CI: 0.85-0.99; p=0.036). However, hypertension had an insignificant mediating role in the Mendelian randomization study., Conclusions: Higher 25(OH)D levels are linked to reduced stroke risk, potentially mediated by hypertension. Prioritizing blood pressure management may improve stroke prevention in 25(OH)D-deficient patients., (© Crown copyright 2024.)

Background: Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels., Method: This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis., Results: We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP., Conclusions: The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yang Ching Chen reports financial support was provided by Taipei Medical University. Yang Ching Chen reports a relationship with Taipei Medical University that includes: employment., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of Interest: Yu P, None; Hu BY, None; He Y, None; Jing L, None; Fan HY, None; Shu J, None; Zeng LZ, None.

DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2 fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This report focuses on the occupational health risks associated with the use of artificial stones containing high levels of crystalline silica in the production of kitchen countertops. It presents the case of a 43-yr-old man who developed severe silicosis due to his occupation involving cutting and polishing quartz stone raw materials. A retrospective analysis of the patient's medical records and occupational history was conducted. The diagnosis of severe silicosis, moderate restrictive lung disease, and bilateral pneumothorax was based on clinical manifestations, pulmonary function test, radiological findings, and histological reports. The patient underwent lung transplantation, and his pulmonary function improved post-surgery. The study highlights the significant health risks associated with procedures involving artificial stones and emphasizes the importance of awareness and protective measures for employees and workers. Clinicians should be cautious when diagnosing respiratory symptoms in patients with a history of occupational exposure to artificial stones containing high levels of crystalline silica.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Mammalian oocyte development depends on the temporally controlled translation of maternal transcripts, particularly in the coordination of meiotic and early embryonic development when transcription has ceased. The translation of mRNA is regulated by various RNA-binding proteins. We show that the absence of cytoplasmic polyadenylation element-binding protein 3 (CPEB3) negatively affects female reproductive fitness. CPEB3-depleted oocytes undergo meiosis normally but experience early embryonic arrest due to a disrupted transcriptome, leading to aberrant protein expression and the subsequent failure of embryonic transcription initiation. We found that CPEB3 stabilizes a subset of mRNAs with a significantly longer 3'UTR that is enriched in its distal region with cytoplasmic polyadenylation elements. Overall, our results suggest that CPEB3 is an important maternal factor that regulates the stability and translation of a subclass of mRNAs that are essential for the initiation of embryonic transcription and thus for embryonic development.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4 DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging., (© 2024. The Author(s).)

Novel therapeutics for the treatment of ischemic stroke remains to be the unmet clinical needs. Previous studies have indicated that salvianolic acid A (SAA) is a promising candidate for the treatment of the brain diseases. However, SAA has poor absolute bioavailability and does not efficiently cross the intact blood-brain barrier (BBB), which limit its efficacy. To this end we developed a brain-targeted liposomes for transporting SAA via the BBB by incorporating the liposomes to a transport receptor, insulin-like growth factor-1 receptor (IGF1R). The liposomes were prepared by ammonium sulfate gradients loading method. The prepared SAA-loaded liposomes (Lipo/SAA) were modified with IGF1R monoclonal antibody to generate IGF1R antibody-conjugated Lipo/SAA (IGF1R-targeted Lipo/SAA). The penetration of IGF1R-targeted Lipo/SAA into the brain was confirmed by labeling with Texas Red, and their efficacy were evaluate using middle cerebral artery occlusion (MCAO) model. The results showed that IGF1R-targeted Lipo/SAA are capable of transporting SAA across the BBB into the brain, accumulation in brain tissue, and sustained releasing SAA for several hours. Administration o IGF1R-targeted Lipo/SAA notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation, which had much higher efficiency than no-targeted SAA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hua-Ying Fan reports financial support was provided by Natural Science Foundation of Shandong Province. Hua-Ying Fan reports a relationship with Natural Science Foundation of Shandong Province that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described. As the underlying mechanism of RNA splicing, splicing factors undergo dramatic maternal-to-zygotic conversion. This conversion relies on the key maternal factors BTG4 and PABPN1L and is zygotic-transcription-dependent. CDK11-dependent phosphorylation of the key splicing factor, SF3B1, and its aggregation with SRSF2 in the subnuclear domains of 2-cell embryos are prerequisites for ZSA. Isoforms generated by erroneous splicing, such as full-length Dppa4, hinder normal embryonic development. Moreover, alternative splicing regulates the conversion of early embryonic blastomeres from totipotency to pluripotency, thereby affecting embryonic lineage differentiation. ZSA is an essential post-transcriptional process of MZT and has physiological significance in generating new life. In addition to transcriptional activation, appropriate expression of transcript isoforms is also necessary for preimplantation embryonic development., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Adult height is associated with the risk of stroke. However, the underlying mechanism remains unclear. We explored the mediating role of metabolic factors in the association between adult height and stroke incidence., Methods: We used data from 3306 community-dwelling participants with complete information on adult height, metabolic factors, and 25-year cardiovascular outcomes. Participants were classified into three adult height groups based on sex-specific height quartiles: short (Q1), average (Q2-Q3), and tall (Q4). The primary endpoint was the occurrence of cardiovascular disease, including coronary artery disease and stroke., Results: Taller adult height was associated with a lower risk of stroke. Compared with the short group the risk of stroke reduced with taller height with a hazard ratio (HR) of 0.68 in the average group (95% confidence interval [CI]: 0.50-0.93), and 0.45 in the tall group (95% CI: 0.31-0.65). Low systolic blood pressure was considered as a protective mediator in the effect of adult height on the risk of stroke in the average (HR: 0.86; 95% CI: 0.82-0.93) and the tall group (HR: 0.85; 95% CI: 0.78-0.91). Systolic blood pressure significantly contributed to height-related stroke risk (proportion mediated: 0.41; 95% CI: 0.19-1.56)., Conclusions: This study found an inverse association between adult height and stroke risk, which is partly driven by lower systolic blood pressure. These findings highlight the importance of systolic blood pressure management as a potential preventive strategy against stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Sex differences in blood pressure (BP) appear during childhood and adolescence, but the role of central precocious puberty (CPP) remains unclear. In this study, we aimed to examine the association of CPP with the risk of early hypertension and BP trajectories in girls and boys., Methods: We analyzed trajectories of BP before and after puberty in girls aged 6-13 years (n = 305) and boys aged 10-15 years (n = 153) in the Taiwan Pubertal Longitudinal Study. The timing of puberty onset was defined as the month at which the children reached Tanner stage 2. We examined the association of CPP with the risk of early hypertension and BP trajectories before and after puberty onset., Results: Among boys, CPP was found to be associated with early hypertension (odds ratio, 7.45 [95% CI, 1.15-48.06]), whereas no such association was observed among girls. Boys with CPP had higher systolic BP than did those with normal puberty onset before puberty onset (mean difference, 6.51 [95% CI, 0.58-12.43]) and after puberty onset (mean difference, 8.92 [95% CI, 8.58-15.26])., Conclusion: A large proportion of the higher systolic BP observed in boys with CPP compared with in those with normal puberty onset is accrued after puberty., Impact: We examined the sex-specific association of central precocious puberty with blood pressure trajectories to better understand whether central precocious puberty was associated with early hypertension. Central precocious puberty was associated with differences in systolic blood pressure trajectories, especially after puberty onset in boys. For boys only, central precocious puberty was associated with early hypertension. A large proportion of the higher systolic blood pressure observed in boys with central precocious puberty compared with in those with normal puberty onset was accrued after puberty. Interventions targeting central precocious puberty are likely to influence systolic blood pressure in early adulthood., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported., Methods: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF., Results: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells., Conclusion: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway., (© 2022 Wiley Periodicals LLC.)

Two new protopanaxadiol type sapogenins, (3 β ,12 β )-3,12,20-trihydroxydammar-24-en-26-al ( 1 ) and (3 β ,12 β )-3,12,20-trihydroxydammar-24-en-26-oic acid ( 2 ), were isolated from the alkali hydrolysate of stems-leaves of Panax notoginseng , along with seven known analogues ( 3 - 9 ). Their structures were elucidated by spectroscopic analyses and single-crystal X-ray diffraction. Compound 2 and the known sapogenins 5 - 8 displayed weak to moderate inhibition of NO production in LPS-induced RAW264.7 macrophages with IC 50 values from 44.5 to 143.6 μM, respectively.

Background: The blood urea nitrogen-to-creatinine ratio (BUNCR) has been proposed as a potential biomarker for critical illness-induced catabolism. However, its specific relevance and significance in the context of non-traumatic intracranial hemorrhage (NTIH) remains unclear. As such, the primary objective of this study was to determine the role of BUNCR in the prognosis of patients with NTIH., Materials and Methods: All data were sourced from the Medical Information Mart for Intensive Care-IV 2.0 (MIMIC-IV) database. Study outcomes included 30-day and 1-year mortality rates. Univariate and multivariate logistic regression analyses were used to calculate adjusted odds ratio with corresponding 95% confidence interval, and generalized additive model were used to identify both linear and non-linear relationships between BUNCR and mortality rates. A two-piecewise regression model was performed to calculate the saturation effect. Subgroup analyses were performed to evaluate outcome stability in various groups., Results: A retrospective study of 3,069 patients with NTIH revealed a U-shaped relationship between BUNCR levels and 30-day/1-year mortality. The two-piecewise regression model showed that the inflection points for 30-day and 1-year mortality were 10.455 and 16.25, respectively. On the left side of the inflection point, the 30-day and 1-year mortality rate decreased by 17.7% (OR = 0.823, 95%CI: 0.705-0.960; p  = 0.013) and 5.3% (OR = 0.947, 95%CI: 0.899-0.999; p  = 0.046), respectively, per 1 unit increment of BUNCR. On the right side of the inflection point, the 30-day and 1-year mortality rate increased by 1.6% (OR = 1.016, 95%CI: 1.000-1.031; p  = 0.046) and 3.6% (OR = 1.036, 95%CI:1.019-1.054; p  < 0.001) per 1 unit decrement of BUNCR. Subgroup analyses revealed consistent results across different strata., Conclusion: This study identified a nonlinear relationship between BUNCR and mortality in patients with NTIH, indicating that BUNCR may be valuable prognostic marker for early identification and proactive management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Jiang, Cai, Fan, Liang, Yuan, Wu, Wang, Cheng and Zhang.)

Aim: To evaluate the clinical significance of checking episcleral venous fluid wave (EVFW) during gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open angle glaucoma (OAG)., Methods: This retrospective case series study comprised 30 patients (45 eyes) with OAG underwent GATT. The location and extent of EVFW were examined and graded after intraoperative compression flushing of the anterior chamber angle during the operation. Patients were followed up for 1y. A complete success for surgery is defined as a postoperative intraocular pressure (IOP) <18 mm Hg without any anti-glaucoma medication. IOP<18 mm Hg with less than two anti-glaucoma medications is defined as qualified success, while the control of IOP requiring three anti-glaucoma medications is considered as unsuccess., Results: The mean IOP was 35.38±7.16 mm Hg before surgery and 15.52±4.22 mm Hg 1y after surgery ( P <0.01). The average number of anti-glaucoma medication was 2.8±1.2 (2-4) preoperation and 0.6±1.3 (0-3) 1y postoperation ( P <0.01). The success rate of the operation was 93.33%. Complete success rate was 66.67%, qualified success rate was 26.67%, and 6.66% of unsuccessful cases required reoperation. EVFW of all cases was grade 2-4, and the percentages of grade 2, 3 and 4 were 33.33%, 40.0% and 26.67%, respectively. The distribution and percentage of EVFW were inferior (36%), nasal (28%), superior (20%), and temporal (16%). The EVFW grade of complete success patients was 3.4±0.6 (3-4), and that of qualified success patients was 2.6±1.0 (2-4). The larger the range of EVFW, the lower the IOP, and the better the IOP reduction effect., Conclusion: During GATT surgery, pressurized irrigation of anterior chamber to check EVFW can reduce the outflow resistance of aqueous humor and increase the effect of postoperative IOP. The range of EVFW is negatively correlated with postoperative IOP. Therefore, EVFW may be a valuable prognostic indicator for the success of GATT surgery., (International Journal of Ophthalmology Press.)

Background: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM., Methods: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis., Results: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively)., Conclusions: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Interfacial polymerization is a well-known process to synthesize separation layers for thin film composite membranes at an immiscible organic liquid-aqueous liquid interface. The organic-aqueous interface determines the diffusion dynamics of monomers and the chemical environment for polymerization, exerting a critical influence on the formation of polymer thin films. This review summarizes recent advances in tailoring interfacial polymerization using interfaces beyond the conventional alkane-water interface to achieve high-performance separation films with designed structures. Diverse liquid-liquid interfaces are introduced for synthesizing separation films by adding co-solvents into the organic phase and/or the aqueous phase, respectively, or by replacing one of the liquid phases with other solvents. Innovative liquid-gel and liquid-gas interfaces are then summarized for the synthesis of polymer thin films for separation. Novel strategies to form reaction interfaces, such as spray-coating, are also presented and discussed. In addition, we discuss the details of how a physically or chemically patterned substrate affects interfacial polymerization. Finally, the potential of unconventional interfaces in interfacial polymerization is forecast with both challenges and opportunities.

Background: We aimed to assess the role of histogram analysis of DCE-MRI parameters for accurately distinguishing renal clear cell carcinoma from renal hamartoma with minimal fat., Methods: Patients with renal tumors were enrolled from January 2013 to December 2015, including renal clear cell carcinoma (n = 39) and renal hamartoma (n = 10). Preoperative DCE-MR Imaging was performed, and whole-tumor regions of interest were drawn to obtain the corresponding histogram parameters, including skewness, kurtosis, frequency size, energy, quartile, etc. Histogram parameters differences between renal clear cell car-cinoma and renal hamartoma with minimal fat were compared. The diagnostic value of each significant parameter in predicting malignant tumors was determined., Results: Histogram parameters of the DCE map contributed to differentiating the benign from malignant renal tumor groups. Histogram analysis of DCE maps could effectively present the heterogeneity of renal tumors and aid in differentiating benign and malignant tumors. ROC analysis results indicated that when frequency size = 1,732 was set as the threshold value, favorable diagnostic performance in predicting malignant tumors was achieved (AUC - 0.964; sensitivity - 84.6%; specificity - 100%), followed by skewness, Energy, Entropy, Uniformity, quartile 5, quartile 50, and kurtosis., Conclusions: Histogram analysis of DCE-MRI shows promise for differentiating benign and malignant renal tumors. Frequency size was the most significant parameter for predicting renal clear cell carcinoma.

To remediate historically polluted sites before their land-use changes, it is essential to understand the concentration distribution, geochemical fraction, and migratory behavior of As in soil with varied particle sizes for the use of a sieving procedure. This study investigated the amount and percentage of As in soil with different particle sizes (0.25, 0.25-1, and 1-2 mm) as well as its toxicity characteristic in leaching procedure at four previously contaminated sites in the Beijiang River Basin, South China. The results showed that the total As concentration in the collected soils ranged from 70.1 to 402.8 mg/kg, and only a few percent of soil particle samples had As contents below the local risk threshold value of 60 mg/kg. The amorphous hydrous oxide bound, crystalline hydrous oxide bound, and residual fractions (F3-F5) of the geochemical fraction of As in soil of polluted sites accounted for 82.2-95.7% of the total As distribution. However, the concentration of As in non-specifically bound fractions increased with the mass ratio of soil with coarse particle sizes due to the negative correlation of Fe-bearing minerals concentration with the mass ratio of soil with coarse particle size. According to redundancy analysis, soil with coarse particle sizes and non-specifically bound As were mostly responsible for the As concentration in the leachate. These findings confirmed that a sieving process was not suitable for the remediation of soil As at four historically contaminated sites in the Beijiang River Basin due to the high concentration of As in soil and non-negligible environmental risk of labile extractable As in soil with coarse particle size., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

MAP4K1 has been identified as a cancer immunotherapy target. Whether and how cancer cell-intrinsic MAP4K1 contributes to glioblastoma multiforme (GBM) progression remains unclear. We found that MAP4K1 was highly expressed in the glioma cells of human GBM specimens. High levels of MAP4K1 mRNA were prevalent in IDH -WT and 1p/19q non-codeletion gliomas and correlated with poor prognosis of patients. MAP4K1 silencing inhibited GBM cell proliferation and glioma growth. Transcriptome analysis of GBM cells and patient samples showed that MAP4K1 modulated cytokine‒cytokine receptor interactions and chemokine signaling pathway, including IL-18R and IL-6R Importantly, MAP4K1 loss down-regulated membrane-bound IL-18R/IL-6R by inhibiting the PI3K-AKT pathway, whereas MAP4K1 restoration rescued this phenotype and therefore GBM cell proliferation. MAP4K1 deficiency abolished GBM cell pro-proliferation responses to IL-18, suggesting an oncogenic role of MAP4K1 via the intrinsic IL-18/IL-18R pathway. In addition, GBM cell-derived MAP4K1 impaired T-cell migration and reduced CD8 + T-cell infiltration in mouse glioma models. Together, our findings provide novel insight into the pathological significance of GBM cell-intrinsic MAP4K1 in driving tumor growth and immune evasion by remodeling cytokine-chemokine networks., (© 2023 Sun et al.)

Background: Omega-3 supplementation has been reported to modulate immune responses and prevent food allergies among children; however, findings are inconsistent, and the timing of supplementation, which is critical, has not been thoroughly investigated., Objective: To assess optimal timing (maternal vs childhood intake) of omega-3 supplementation for reducing food allergy risk among children in 2 periods (the first 3 years and beyond 3 years of age)., Methods: We performed a meta-analysis to assess the effects of maternal or childhood omega-3 supplementation on preventing the development of infant food allergies and food sensitizations. The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were searched for related studies published until October 30, 2022. We conducted dose-response and subgroup analyses to investigate the effects of omega-3 supplementation., Results: We found that maternal omega-3 supplementation during pregnancy and lactation was significantly associated with decreased risks of infant egg sensitization (relative risk [RR]: 0.58, 95% confidence interval [95% CI]: 0.47-0.73, P < .01) and peanut sensitization (RR: 0.62, 95% CI: 0.47-0.80, P < .01) among children. Similar results were found in subgroup analyses for food allergy, egg sensitization, and peanut sensitization during the first 3 years of age and peanut sensitization and cashew nut sensitization beyond 3 years of age. Dose-response analysis showed a linear relationship between maternal omega-3 supplementation and infant egg sensitization risk during early life. By contrast, intake of omega-3 polyunsaturated fatty acid during childhood did not appear to significantly protect against food allergies., Conclusions: Maternal omega-3 supplementation during pregnancy and lactation, rather than childhood intake, reduces the risk of infant food allergy and food sensitization., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics., Objectives: Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process., Methods: In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry., Results: R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage., Conclusion: The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Context: Extremely early age at menarche, also called precocious puberty, has been associated with various cardiometabolic traits, but their shared heritability remains unclear., Objectives: This work aimed to identify new shared genetic variants and their pathways for age at menarche and cardiometabolic traits and to investigate the influence of central precocious puberty on childhood cardiometabolic traits., Methods: Using the conjunction false discovery rate method, this study analyzed genome-wide association study data from the menarche-cardiometabolic traits among 59 655 females of Taiwanese ancestry and systemically investigated pleiotropy between age at menarche and cardiometabolic traits. To support the novel hypertension link, we used the Taiwan Puberty Longitudinal Study (TPLS) to investigate the influence of precocious puberty on childhood cardiometabolic traits., Results: We discovered 27 novel loci, with an overlap between age at menarche and cardiometabolic traits, including body fat and blood pressure. Among the novel genes discovered, SEC16B, CSK, CYP1A1, FTO, and USB1 are within a protein interaction network with known cardiometabolic genes, including traits for obesity and hypertension. These loci were confirmed through demonstration of significant changes in the methylation or expression levels of neighboring genes. Moreover, the TPLS provided evidence regarding a 2-fold higher risk of early-onset hypertension that occurred in girls with central precocious puberty., Conclusion: Our study highlights the usefulness of cross-trait analyses for identifying shared etiology between age at menarche and cardiometabolic traits, especially early-onset hypertension. The menarche-related loci may contribute to early-onset hypertension through endocrinological pathways., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Efficient repair of oxidized DNA is critical for genome-integrity maintenance. Cockayne syndrome protein B (CSB) is an ATP-dependent chromatin remodeler that collaborates with Poly(ADP-ribose) polymerase I (PARP1) in the repair of oxidative DNA lesions. How these proteins integrate during DNA repair remains largely unknown. Here, using chromatin co-fractionation studies, we demonstrate that PARP1 and PARP2 promote recruitment of CSB to oxidatively-damaged DNA. CSB, in turn, contributes to the recruitment of XRCC1, and histone PARylation factor 1 (HPF1), and promotes histone PARylation. Using alkaline comet assays to monitor DNA repair, we found that CSB regulates single-strand break repair (SSBR) mediated by PARP1 and PARP2. Strikingly, CSB's function in SSBR is largely bypassed when transcription is inhibited, suggesting CSB-mediated SSBR occurs primarily at actively transcribed DNA regions. While PARP1 repairs SSBs at sites regardless of the transcription status, we found that PARP2 predominantly functions in actively transcribed DNA regions. Therefore, our study raises the hypothesis that SSBR is executed by different mechanisms based on the transcription status., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants., (© 2023 The Scandinavian Foundation for Immunology.)

MicroTom has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g. arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs, and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on MicroTom, and this database should be of great value to those who want to adopt MicroTom as a model plant for research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Human oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. However, the genetic factors underlying this human disease remain largely unknown. The spindle assembly checkpoint (SAC) is an intricate surveillance mechanism that ensures accurate segregation of chromosomes throughout cell cycles. Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known as p31 comet , binds mitosis arrest deficient 2 (MAD2) and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell-cycle progression. In this study, by whole-exome sequencing (WES), we identified homozygous and compound heterozygous MAD2L1BP variants in three families with female patients diagnosed with primary infertility owing to oocyte metaphase I (MI) arrest. Functional studies revealed that the protein variants resulting from the C-terminal truncation of MAD2L1BP lost their binding ability to MAD2. cRNA microinjection of full-length or truncated MAD2L1BP uncovered their discordant roles in driving the extrusion of polar body 1 (PB1) in mouse oocytes. Furthermore, the patient's oocytes carrying the mutated MAD2L1BP resumed polar body extrusion (PBE) when rescued by microinjection of full-length MAD2L1BP cRNAs. Together, our studies identified and characterized novel biallelic variants in MAD2L1BP responsible for human oocyte maturation arrest at MI, and thus prompted new therapeutic avenues for curing female primary infertility., Competing Interests: LH, WL, XD, SZ, BX, FW, RJ, LL, LW, XJ, YC, JZ, CX, XT, HF, HZ, JB No competing interests declared, (© 2023, Huang, Li, Dai et al.)

Purpose: Prepubescent body fat percentage (BFP) is associated with puberty onset; however, the association between the timing of puberty onset and BFP remains unclear. This study aimed to determine whether and how the timing of puberty onset is associated with various anthropometric measures, and to investigate the critical time period of the BFP transition before and after puberty., Methods: The Taiwan Pubertal Longitudinal Study (TPLS) has a multicenter, population-based prospective cohort and was established in July 2018 at 4 pediatric departments. We included girls aged 6-14 years and boys aged 9-17 years evaluated as having puberty onset and excluded those with precocious puberty diagnosis. The anthropometric measures were collected every 3 months. The main outcome was age at puberty onset. Data were analyzed between July 2018 and September 2020., Results: For 153 girls and 83 boys, BFP was significantly related to puberty onset for girls. Longitudinal analysis revealed that BFP in the girls was reduced to less than 18% 6 months before puberty and rapidly increased by 2.85% over 3 months, then exceeding 20% before puberty onset. After puberty onset, BFP was no longer lower than 22%., Conclusions: BFP is an essential predictor of age at puberty onset. BFP first decreases and then begins to increase 3-6 months before puberty in girls. Parents and schools could monitor the BFP of prepubescent girls every 6 months to predict puberty onset., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74 -/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PL PNs -dSTR FSIs ) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PL PNs -BLA PNs ) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity., (© 2023. The Author(s).)

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Jackfruit ( Artocarpus heterophyllus ) is widely cultivated in the tropical areas in the world. Jackfruit bark split disease occurred in the large-scale plantations of 18 cities and counties surveyed in Hainan since 2021, among which the incidence rate of serious orchards reached about 70%, and the mortality rate reached about 35%. Jackfruit bark split disease mainly harms tree branches and trunks, manifested as water stains, bark gumming, bark depression, bark cracking, and ultimately plant death. To identify the pathogen, Four samples with jackfruit bark split disease symptoms were collected, sterilized with 75% ethanol for 30 s, then soaked in 2% sodium hypochlorite (NaClO) for 5 mins, and finally rinsed continuously with sterilized distilled water. The sterilized tissues were placed on LB agar medium and incubated in illumination incubator at 28 ℃. Four milky white, round with neat edges, convex and smooth, translucent colonies were obtained. All isolates (JLPs-1 to JLPs-4) were Gram-negative, negative for oxidase, catalase and gelatin liquefaction. Amplification and sequencing of 16S rDNA gene from 4 isolates were conducted with the universal primers 27f /1492r (Lane et al. 1991). The BLASTn analysis of obtained JLPs-1 and JLPs-3 sequences (GenBank accession nos. OP942452 and OP942453) showed an identity percentage of 98.99% and 98.93% with Pectobacterium sp. (CP104733), respectively. Phylogenetic analysis based on 16S rDNA gene using the neighbor-joining method with MEGA 7.0 software revealed that JLPs-1 and JLPs-3 were clustered together with P. carotovorum reference strains. The four housekeeping genes gyrA, recA, rpoA and rpoS were partially sequenced for JLPs-1 isolates using primers gyrA1/gyrA4, recA1/recA2c, rpoS1/rpoS2 and rpoA F1/rpoA R1 (Loc et al. 2022), respectively. Multilocus sequence analyses identified the isolates from jackfruit as P. carotovorum . To further confirm the identification of Pectobacterium carotovorum , pelY gene, P. carotovorum subsp. Brasiliensis 16S-23S intergenic region ( Pcb IGS ) and P. carotovorum subsp. carotovorum ( Pcc ) specific fragment were amplified with primers Y1/Y2 (Darrasse et al. 1994), BR1f/L1r (Duarte et al. 2004) and EXPCCF/EXPCCR (Kang et al. 2003), respectively. A 540 bp target fragment was successfully amplified from JTPs only by EXPCCF/EXPCCR and there no bands for the other two primers. Pathogenicity test was performed in the field, and all the inoculated trees were 2-3-year-old 'Qiong Yin No.1' variety. Dense small holes were pierced with sterilized inoculation needle on four healthy jackfruit trees. Then punctured wounds were spraying-inoculated with bacteria suspension of JLPs-1 (108 CFU/ml), and finally wrapped with plastic wrap to moisturize. Two trees inoculated with sterile distilled water served as negative control. Typical symptoms of bark gumming, bark depression, bark cracking were observed on all of the inoculated trees at 17 dpi which just similar to those originally caused by P. carotovorum in the field, whereas negative control trees remained asymptomatic. The strains were re-isolated successfully from symptomatic jackfruit trees and were consistent with the biological and molecular biological characteristics of original strains, confirming that the pathogen of jackfruit bark split disease was Pectobacterium carotovorum . To our knowledge, this is the first report of P. carotovorum causing bark split disease on jackfruit in China.

To study of premature/early death of autistic patients from the perspective of life course can help families, medical institutions and policy makers better deal with the adverse effects of autism. Several studies have shown that autistic patients have a high risk of death, however, the results are still inconsistent. To assess the risk of mortality among the autistic patients, we undertook a comprehensive search of MEDLINE, Web of Science and EMBASE databases. This paper reviewed the studies on the negative disease outcomes of autism spectrum disorders, including the risk of death, causes of death and several research hotspots in this field. Strict inclusion/exclusion criteria were used. Information was extracted from selected papers, tabulated and synthesized. In the study, 15 studies were included, with a total of 216 045 individuals. The main outcome was all-cause mortality in association with autism and the secondary outcome was cause-specific mortality. The results showed that all-cause mortality was higher for the autistic patients ( RR =2.32, 95% CI : 1.98-2.72, I 2 =87.1%, P < 0.001). Risk ratio showed a greater inequality for female than male (male: RR =2.00, 95% CI : 1.57-2.55, I 2 =93.2%, P < 0.001; female: RR =4.66, 95% CI : 3.30-6.58, I 2 =92.0%, P < 0.001). Compared with the unnatural death, the risk of natural death was higher ( RR =3.44, 95% CI : 1.27-9.26, I 2 =80.2%, P =0.025). As autism had many comorbidities, which would bring more health risks and natural deaths possibilities. There were some structural differences in unnatural death. Accidental injury death and suicide were two kinds of causes. Lacking social skills would weaken the ability to ask for help when encountering injuries. This paper put forward some suggestions for futures. First, to well study the comorbidity can reduce the risk of death from a medical point of view. Second, the scientists and policymakers should pay attention to the social environment and provide a safer environment for the autistic patients. Third, for women and for adolescents without cognitive impairment, due to their high risk of suicide, the society should provide them with more supportive social networks and improve their life satisfaction. Fourth, it is necessary to balance the rehabilitation resources in various regions in China and provide more high-quality lifelong rehabilitation monitoring and care services.

Objectives: Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3'-O-β-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG., Methods: In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins., Key Findings: The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKβ and yet up-regulated IκBα expression by western blot analysis., Conclusions: Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aimed to investigate the efficacy of Traditional Chinese Herbs (TCH) combined with bioelectrical stimulation (BES) on patients with kidney deficiency and blood stasis type thin endometrium., Patients and Methods: A retrospective observational study was conducted on 83 patients diagnosed with thin endometrium, treated in our hospital from August 2019 to August 2021. The clinical data of the patients were reviewed, and 60 eligible patients were categorized into two groups based on the treatment they received: the TCH-BES group (n=30, patients received Femoston, TCH and BES treatment) and the control group (n=30, patients received Femoston only). The endometrial thickness (EMT), uterine artery resistance index (RI) and pulsatility index (PI), serum reproductive hormone levels, traditional Chinese medicine (TCM) syndrome scores, and clinical pregnancy outcomes between the two groups were compared. Continuous data were described as mean ± standard deviation (X- ± S). Student's t-test was used for comparison between the two groups and paired-sample t-test was used for comparison within the same group before and after the treatment., Results: A total of 60 patients with thin endometrium, aged 20-35 years (average, 31.67±3.19 years), were included in this study. After the treatment, the EMT, E2 and progesterone (P) levels of the TCH-BES group were higher than that of the control group (p<0.001, p<0.05 and p<0.001, respectively), the PI, RI level and TCM syndrome scores of the TCH-BES group were lower than those of the control group (p<0.001). The clinical efficacy and pregnancy rate in the TCH-BES group were significantly higher than those in the control group (p<0.05)., Conclusions: TCH combined with EBS has a satisfactory efficacy on patients with kidney deficiency and blood stasis type thin endometrium, and improves EMT, E2 and P levels, reduces PI, RI and TCM syndrome, and eventually leads to a favorable clinical pregnancy outcome.

Saururus chinensis, an herbaceous magnoliid without perianth, represents a clade of early-diverging angiosperms that have gone through woodiness-herbaceousness transition and pollination obstacles: the characteristic white leaves underneath inflorescence during flowering time are considered a substitute for perianth to attract insect pollinators. Here, using the newly sequenced S. chinensis genome, we revisited the phylogenetic position of magnoliids within mesangiosperms, and recovered a sister relationship for magnoliids and Chloranthales. By considering differentially expressed genes, we identified candidate genes that are involved in the morphogenesis of the white leaves in S. chinensis. Among those genes, we verified - in a transgenic experiment with Arabidopsis - that increasing the expression of the "pseudo-etiolation in light" gene (ScPEL) can inhibit the biosynthesis of chlorophyll. ScPEL is thus likely responsible for the switches between green and white leaves, suggesting that changes in gene expression may underlie the evolution of pollination strategies. Despite being an herbaceous plant, S. chinensis still has vascular cambium and maintains the potential for secondary growth as a woody plant, because the necessary machinery, i.e., the entire gene set involved in lignin biosynthesis, is well preserved. However, similar expression levels of two key genes (CCR and CAD) between the stem and other tissues in the lignin biosynthesis pathway are possibly associated with the herbaceous nature of S. chinensis. In conclusion, the S. chinensis genome provides valuable insights into the adaptive evolution of pollination in Saururaceae and reveals a possible mechanism for the evolution of herbaceousness in magnoliids., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Objective: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate acupuncture's clinical effect on insulin resistance (IR) in women with polycystic ovary syndrome (PCOS)., Methods: PubMed, Cochrane Library, Embase databases, and Chinese databases, including China National Knowledge Infrastructure, Technology Journal Database, and Wanfang Database, were searched without language restrictions from inception to December 20, 2021. Only RCTs in which acupuncture had been examined as the sole or adjunctive PCOS-IR treatment were included. Our primary endpoint was the homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were fasting blood glucose (FBG), fasting insulin (FINS), body mass index (BMI), and adverse events., Results: Our analysis included 17 eligible RCTs (N = 1511 participants). Compared with other treatments, acupuncture therapy yielded a greater mean reduction in HOMA-IR (MD = -0.15; 95% CI, -0.27 to -0.03; P = 0.01) and BMI (MD = -1.47; 95% CI, -2.46 to -0.47; P = 0.004). Besides acupuncture was associated with a lower risk of adverse events than other treatments (RR, 0.15; 95% CI, 0.10 to 0.22; P < 0.01). Additionally, the combination treatment of acupuncture and medicine is more effective in improving HOMA-IR (MD = -0.91; 95% CI, -1.11 to -0.71; P < 0.01), FBG (MD = -0.30; 95% CI, -0.56 to -0.04; P = 0.02), FINS (MD = -2.33; 95% CI, -2.60 to -2.06; P < 0.01) and BMI (MD = -1.63; 95% CI, -1.94 to -1.33; P < 0.01) than medicine alone., Conclusions: Acupuncture is relatively effective in improving HOMA-IR and BMI in PCOS-IR. Besides, it's safer than other treatments and could be an adjuvant strategy for improving PCOS-IR. Further large-scale, long-term RCTs with strict methodological standards are justified., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Jackfruit (Artocarpus heterophyllus) is an important tropical commercial fruit crop grown in Hainan province, China. In recent years, severe jackfruit bronzing disease has been found in 11 cities and counties in Hainan. On average, 80% of trees in a jackfruit orchard are affected once bronzing disease is detected. The disease is characterized by yellow-orange to reddish discoloration of the pulp and rags of infected fruit (Hernández-Morales et al. 2017). Jackfruit bronzing disease has been reported previously in the Philippines (Gapasin et al. 2012), Malaysia (Zulperi et al. 2017), and Mexico (Hernández-Morales et al. 2017). Diseased samples of jackfruit 'Tai Eight' with the bronzing symptoms were collected from a plantation in Changjiang, Hainan. The samples were sterilized with 75% ethanol for 30 s, then soaked with 1% sodium hypochlorite for 8 min, and rinsed with sterilized distilled water. The sterilized tissues were ground in 2 mL sterile water, and allowed to stand for 30 min. Then, 500 μL of the supernatant was spread on Glucose-Yeast agar medium and incubated overnight at 28ºC. Representative bacterial colonies were lemon-yellow, convex and smooth, transparent with entire edges. Colonies were Gram-negative, positive for catalase and gelatin liquefaction, which were consistent with the characteristics of P. stewartii subsp. stewartii. In PCR amplifications, an 920 bp amplicon of strain JTPE2 with the primers ES16/ESIG2c (Coplin et al. 2002) and an 1100 bp amplicon of strain JTPC2 with the primers CPSL1/CPSR2c (Ibrahim et al. 2019) were obtained, whereas no bands were observed for the negative control samples. The ES16/ESIG2c and CPSL1/CPSR2c fragments were sequenced for nucleotide BLAST (BLASTn) searches of the NCBI database and phylogenetic tree construction. The obtained ES16/ESIG2c sequences (SAR accession no. SRR22405292) showed 99.07%-99.60% similarity with P. stewartii subsp. stewartii (CP017581, AJ311838 and MF598163). The obtained CPSL1/CPSR2c sequences (SAR accession no. SRR22405293) showed 99.40%-99.99% similarity with P. stewartii subsp. stewartii (MW971422, MH752485 and MH257287). Phylogenetic analysis based on cpsDE sequences (Ibrahim et al. 2019) using the maximum likelihood method revealed that strains JTPE2 and JTPC2 were clustered together with P. stewartii subsp. stewartii. A pathogenicity test was conducted by injecting 2 mL of 108 CFU/ml bacterial suspension into pulp from healthy, surface-sterilized jackfruit. Pulp injected with sterilized distilled water served as a negative control. All inoculated samples produced bronzing symptoms from 2-3 weeks post-inoculation similar to the field-observed symptoms, whereas control fruit were asymptomatic. The strains were reisolated from symptomatic jackfruit pulp to complete Koch's postulates. The bacterial suspension was inoculated on 2-week-old maize seedlings to supplement in vivo pathogenicity testing. Typical Stewart's disease leaf symptoms were visible at 2 weeks post-inoculation. Based on morphological, biochemical, and physiological evidence, pathogenicity tests, and molecular analyses, the pathogenic bacterium isolated from 'Tai Eight' jackfruit was identified as P. stewartii subsp. stewartii. To our knowledge, this is the first report of bronzing disease caused by P. stewartii subsp. stewartii on jackfruit in China, which may assist in preventing the global spread of jackfruit bronzing disease.

Background: Left ventricular mass is a highly heritable disease. Previous studies have suggested common genetic variants to be associated with left ventricular mass; however, the roles of rare variants are still unknown. We performed targeted next-generation sequencing using the TruSight Cardio panel, which provides comprehensive coverage of 175 genes with known associations to 17 inherited cardiac conditions. Methods: We conducted next-generation sequencing using the Illumina TruSight Cardiomyopathy Target Genes platform using the 5% and 95% extreme values of left ventricular mass from community-based participants. After removing poor-quality next-generation sequencing subjects, including call rate <98% and Mendelian errors, 144 participants were used for the analysis. We performed downstream analysis, including quality control, alignment, coverage length, and annotation; after setting filtering criteria for depths more than 60, we found a total of 144 samples and 165 target genes for further analysis. Results: Of the 12,287 autosomal variants, most had minor allele frequencies of <1% (rare frequency), and variants had minor allele frequencies ranging from 1% to 5%. In the multi-allele variant analyses, 16 loci in 15 genes were significant using the false discovery rate of less than .1. In addition, gene-based analyses using continuous and binary outcomes showed that three genes ( CASQ2 , COL5A1 , and FXN ) remained to be associated with left ventricular mass status. One single-nucleotide polymorphism (rs7538337) was enriched for the CASQ2 gene expressed in aorta artery ( p = 4.6 × 10-18), as was another single-nucleotide polymorphism (rs11103536) for the COL5A1 gene expressed in aorta artery ( p = 2.0 × 10-9). Among the novel genes discovered, CASQ2 , COL5A1 , and FXN are within a protein-protein interaction network with known cardiovascular genes. Conclusion: We clearly demonstrated candidate genes to be associated with left ventricular mass. Further studies to characterize the target genes and variants for their functional mechanisms are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Lin, Lu, Chen, Hsu, Yu, Su, Lin, Chen and Chien.)

Background: Menarche timing may not be directly associated with the risk of coronary artery disease (CAD). Therefore, we investigated the roles of metabolic factors in explaining the effect of age at menarche on CAD risk., Methods: We identified women with age at menarche and CAD by using three analytical methods: Mendelian randomization (MR), logistic regression analysis, and Cox proportional hazard regression. The first two analyses were performed in the Taiwan Biobank ( N = 71,923) study, and the last analysis was performed in the Chin-Shan Community Cardiovascular Cohort study ( N = 1,598). We further investigated the role of metabolic factors in mediating the effect of age at menarche on CAD risk by using three complementary methods with mediation analyses., Results: One standard deviation of earlier age at menarche was associated with a 2% higher CAD risk [odds ratio = 1.02, 95% confidence interval (CI) = 1.001-1.03] in the MR analysis, an 11% higher risk (odds ratio = 1.11, 95% CI = 1.02-1.21) in the logistic regression analysis, and a 57% higher risk (hazard ratio = 1.57, 95% CI = 1.12-2.19) in the Cox proportional hazard regression. All the analyses consistently supported the role of systolic blood pressure in mediating this effect. The MR results indicated that 29% (95% CI = 26%-32%) of the effect of genetically predicted earlier age at menarche on CAD risk was mediated by genetically predicted systolic blood pressure., Conclusion: The results obtained using different analytical methods suggest that interventions aimed at lowering systolic blood pressure can reduce the cases of CAD attributable to earlier age at menarche., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Huang, Chen, Hsu, Li, Su, Lin, Chien and Chen.)

Although the burden of malaria has been successfully controlled globally, this disease remains a major public health issue. To date, neither existing drugs nor vaccines against malaria are sufficient in eliminating malaria worldwide. To achieve the eradication of malaria by 2040, effective interventions targeting all Plasmodium species are urgently needed. As the cornerstone of vaccine design, immune memory serves a significant role in the host's defense against Plasmodium infections. It has long been considered that innate immunity is non-specific and lacks immunologic memory. However, emerging evidence has suggested that innate immunity can be trained following exposure of the body to infectious agents, such as Plasmodium or its products, which, in turn, promotes the onset of a type of memory in innate immune cells. The above "trained" innate immune cells, whose phenotype is modified in response to epigenetic modifications, metabolic recombination, or cytokine secretion, exhibit differential pathophysiology after the exposure of the body to a pathogen. In addition, Plasmodium -infected red blood cells and other host cells can secrete exosomes that contain conserved parasite-specific information, such as proteins, RNA, non-coding RNA molecules, and nucleic acids. These molecules can act as stimuli for promoting the establishment of "trained" innate immunity against malaria, thereby altering the onset and progression of the parasitic disease. A deeper understanding of the role of exosomes in the development of "trained" innate immunity during Plasmodium infection could provide novel therapeutic and prevention strategies against malaria infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The efficacy of surface electroencephalographic neurofeedback (EEG-NF) for improving attentional performance assessed by laboratory measures in patients with attention-deficit/hyperactivity disorder (ADHD) remains unclear., Methods: Following the PRISMA guidelines, the PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials on the efficacy of surface EEG-NF against ADHD focusing on attentional performance evaluated by laboratory measures from inception to January 2022., Results: Fourteen eligible studies were analyzed. Of the 718 participants involved, 429 diagnosed with ADHD received EEG-NF treatment. Significant improvement in attentional performance in ADHD subjects receiving EEG-NF was noted compared to their comparators (p < 0.01). Besides, there was a significant EEG-NF-associated beneficial effect on sustained attention (Hedges' g = 0.32, p < 0.01), whereas the impact on selective attention (p = 0.57) and working memory (p = 0.59) was limited. Moreover, protocol including beta wave enhancement was superior to that only focusing on reducing theta/beta ratio or modulation of slow cortical potential. Subgroup analyses showed that three sessions per week of EEG-NF produced the best effect, while the efficacy of surface EEG-NF was much poorer (Hedges' g = 0.05) when only studies that blinded their participants from knowledge of treatment allocation were included. No significant difference was noted in the improvement of attentional performance 6-12 months after EEG-NF intervention (n = 3, p = 0.42)., Conclusions: Our results demonstrated the satisfactory effectiveness of surface EEG-NF for improving sustained attention, especially when beta wave enhancement was included, despite its failure to sustain a long-term effect. Further large-scale trials are warranted to support our findings., (© 2022. The Author(s).)

The subcortical maternal complex (SCMC), composed of several maternal-effect genes, is vital for the development of oocytes and early embryos. Variants of SCMC-encoding genes (NLRP2, NLRP5, TLE6, PADI6, and KHDC3L, but not OOEP and ZBED3) are associated with human oocyte maturation dysfunction, fertilization failure, and early embryonic arrest. In this study, we enrolled 118 Chinese patients who experienced recurrent preimplantation embryonic arrest during assisted reproductive technology treatments and performed whole-exome sequencing. We discovered compound heterozygous missense variants (c.110G>C and c.109C>G) in the OOEP gene in one patient who experienced recurrent preimplantation embryonic arrest. Arrested embryos from this affected patient were analyzed by single-cell RNA sequencing, which showed a downregulated transcriptome. In addition, six novel NLRP5 variants (c.971T>A, c.3341T>C, c.1575&#95;1576delAG, c.1830&#95;1831delGT, c.1202C>T, and c.2378T>G) were identified in four patients with arrested and severely fragmented embryos. These suspicious mutations were examined by in vitro studies in HEK293T cells. Western blot analysis and immunofluorescence experiments showed that OOEP and partial NLRP5 mutations caused decreased protein levels. Our findings first demonstrated that biallelic variants in OOEP gene could also cause human early embryonic arrest, similar to other SCMC components. We expanded the genetic mutation spectrum of SCMC genes related to early embryogenesis in humans, especially early embryonic arrest., (© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)

Objective: To investigate the changes of brain network characteristics in patients with depression before and after precise repetitive transcranial magnetic stimulation (rTMS) treatment. Methods: Patients with depression in the Second Affiliated Hospital of Xinxiang Medical University and healthy volunteers in the community of Xinxiang city from February 2018 to March 2019 were simultaneously recruited. The left dorsolateral prefrontal cortex was precisely selected as the stimulation target through the latest Human Brainnetome Atlas, and the near infrared navigation was used to achieve accurate brain stimulation treatment in combination with the structural magnetic resonance data. Moreover, functional connectivity was analyzed before and after rTMS treatment in significantly altered brain areas of patients with depression. Results: Nineteen patients (11 males and 8 females) with depression were included, aged (34±11) years. Meanwhile, 22 healthy controls (9 males and 13 females), aged (30±9) years, were also enrolled. Functional connectivity of insular cortex was decreased in depression patients when the insula was analyzed as the target area ( P <0.05). The functional connection from insula to middle frontal lobe and superior parietal lobe in patients with depression decreased before rTMS treatment ( P <0.05), but increased after rTMS treatment ( P <0.05). The functional connection between dIg&#95;L of the insula and the right middle prefrontal lobe was correlated with Beck Anxiety Index (BAI) before rTMS treatment and Beck Depression Index (BDI) after rTMS treatment ( r =0.737, P =0.003; r =0.696, P =0.005). Conclusions: Abnormal functional connectivity of insula may be the brain imaging mechanism of rTMS treatment. Precise brain region selection based on Human Brainnetome Atlas provides a new technical method for clinical rTMS precision treatment.