SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.

OBJECTIVE: Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified many metabolic functions, including regulating the hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus we investigated the function of SMEK1 in white adipose tissue and glucose uptake. METHODS: GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of SVFs and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. RESULTS: We elucidated that SMEK1 was correlated to obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity, had protective effects on metabolic disorders including insulin resistance and inflammation. Smek1 KO mice have lower level of fasting serum glucose, we found that SMEK1 ablation promoted glucose uptake by increased p-AMPKα(T172) and the transcription of Glut4, when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). CONCLUSION: Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.

Ziyuglycoside II attenuated OVX mice bone loss via inflammatory responses and regulation of gut microbiota and SCFAs.

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

A Fluorination Strategy and Low-Acidity Anchoring Group in Self-Assembled Molecules for Efficient and Stable Inverted Perovskite Solar Cells.

Herein, we synthesized two donor-acceptor (D-A) type small organic molecules with self-assembly properties, namely MPA-BT-BA and MPA-2FBT-BA, both containing a low acidity anchoring group, benzoic acid. After systematically investigation, it is found that, with the fluorination, the MPA-2FBT-BA demonstrates a lower highest occupied molecular orbital (HOMO) energy level, higher hole mobility, higher hydrophobicity and stronger interaction with the perovskite layer than that of MPA-BT-BA. As a result, the device based-on MPA-2FBT-BA displays a better crystallization and morphology of perovskite layer with larger grain size and less non-radiative recombination. Consequently, the device using MPA-2FBT-BA as hole transport material achieved the power conversion efficiency (PCE) of 20.32% and remarkable stability. After being kept in an N2 glove box for 116 days, the unsealed PSCs' device retained 93% of its initial PCE. Even exposed to air with a relative humidity range of 30±5% for 43 days, its PCE remained above 91% of its initial condition. This study highlights the vital importance of the fluorination strategy combined with a low acidity anchoring group in SAMs, offering a pathway to achieve efficient and stable PSCs.

Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma.

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

Visually evaluating drug efficacy in living cells using COF-based fluorescent nanoprobe via CHA amplified detection of miRNA and simultaneous apoptosis imaging.

BACKGROUNDS: Cancer is a highly fatal disease which is close relative of miRNA aberrant expression and apoptosis disorders. Elucidation of the therapeutic efficacy through investigating the changes in miRNA and apoptosis holds immense importance in advancing the development of miRNA-based precision therapy. However, it remains a challenge as how to visually evaluate the efficacy during protocol optimization of miRNA-based anticancer drugs at the cellular level. Therefore, exploring effective and noninvasive methods for real-time monitoring of therapeutic efficacy in living cells is of great significance. RESULTS: Herein, we reported a novel fluorescent nanoprobe COF-H1/H2-Peptide for visually evaluating drug efficacy in living cells through amplified imaging of low-abundant miRNA-221 with catalytic hairpin assembly (CHA) circle amplification, as well as simultaneous caspase-3 imaging. With strong stability and good biocompatibility, this newly fabricated amplified nanoprobe showed high sensitivity and specificity for the detection of miRNA-221 and caspase-3, and the limit of detection (LOD) of miRNA-221 was as low as 2.79 pM. The fluorescent imaging results showed that this amplified nanoprobe could not only detect caspase-3 in living cells, but also effectively detect low levels of miRNA-221 with increasing anticancer drug concentration and treatment time. The smart nanoprobe had effective performance for optimizing miRNA-based drug treatment schedules by dual-color fluorescence imaging. SIGNIFICANCE: This nanoprobe combined CHA amplified detection of intracellular miRNA-221 and synchronous apoptosis imaging, with excellent sensitivity for the detection of cellular low-level miRNA, enabling the realization of real-time assessment of the efficacy of miRNA-based therapy in living cells. This work presents a promising approach for revealing the regulatory mechanisms between miRNAs and apoptosis in cancer occurrence, development, and treatment.

[Screening value and correlation of body measurement indices for metabolic syndrome in the population undergoing physical examinations in Chengdu during 2018-2020].

OBJECTIVE: To investigate the screening value and correlation of body measurement indicators for metabolic syndrome(MS) and to provide evidence for MS screening. METHODS: Through a cross-sectional research approach, data from individuals aged 18 and above who participated in health examinations at the North Health Management Center of Sichuan Provincial People's Hospital from 2018 to 2020 were reviewed. Data including height, weight, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking history, and alcohol consumption history were collected. Subsequently, a body shape index(ABSI), body roundness index(BRI), body adiposity index(BAI), abdominal volume index(AVI), relative fat mass index(RFM), and body mass index(BMI) were computed. The individuals were then divided into MS and non-MS groups. The value of body measurement indices in screening for MS in the population aged 18 and above was assessed using ROC curves. Regression analysis was employed to explore the correlation between body measurement indices and MS. RESULTS: A total of 73 411 valid health examination data were obtained, including 44 426 males and 28 985 females. The MS group comprised 9181 males(21%) and 1668 females(6%). In the comparison between the MS and non-MS groups, there were statistically significant differences in ABSI((0.08±0.00) vs. (0.08±0.00)), BRI((4.95±0.67) vs. (4.17±0.68)), BAI((28.08±3.52) vs. (26.39±3.39)), AVI((17.51±2.77) vs. (12.85±2.91)), BMI((27.15±2.99) vs. (23.00±3.04)) and RFM((29.77±5.35) vs. (27.13±6.39))(P<0.05). Univariate Logistic regression analysis showed that ABSI(OR=2.303, 95%CI 1.190-4.457), BRI(OR=4.596, 95%CI 4.446-4.752), BAI(OR=1.144, 95%CI 1.137-1.151), AVI(OR=1.668, 95%CI 1.652-1.684), RFM(OR=1.067, 95%CI 1.064-1.071) and BMI(OR=1.516, 95%CI 1.503-1.528) were associated with MS(P<0.05). Multifactorial Logistic regression analysis corrected for sex, age, smoking and alcohol consumption showed that ABSI(OR=1.767, 95% CI 4.237-7.371), BRI(OR=5.441, 95% CI 5.228-5.663), BAI(OR=1.269, 95% CI 1.260-1.279), AVI(OR=1.648, 95% CI 1.631-1.665), RFM(OR=1.504, 95% CI 1.491-1.517) and BMI(OR=1.508, 95% CI 1.495-1.522) were associated with MS(P<0.05). The ROC curve analysis showed that in adults, the AVI had the highest screening value for MS in males(AUC=0.855, optimal cutoff value=16.18), followed by RFM(AUC=0.844, optimal cutoff value=25.71), BMI(AUC=0.811, optimal cutoff value=25.21), BRI(AUC=0.793, optimal cutoff value=4.39), BAI(AUC=0.709, optimal cutoff value=25.88), and ABSI(AUC=0.671, optimal cutoff value=0.08). In adult females, the RFM had the highest screening value for MS(AUC=0.918, optimal cutoff value=37.01), followed by AVI(AUC=0.911, optimal cutoff value=13.43), BRI(AUC=0.901, optimal cutoff value=4.71), BMI(AUC=0.860, optimal cutoff value=23.94), ABSI(AUC=0.804, optimal cutoff value=0.08), and BAI(AUC=0.797, optimal cutoff value=29.92). CONCLUSION: ABSI, BRI, BAI, AVI, BMI and RFM are all capable of screening for MS. Among males, AVI has the highest screening value for MS, followed by RFM, BMI, BRI, BAI and ABSI. Among females, RFM has the highest screening value for MS, followed by AVI, BRI, BMI, ABSI and BAI. ABSI, BRI, BAI, AVI, RFM and BMI are positively correlated with MS.

Establishment of an induced pluripotent stem cell (iPSC) line (INNDSUi005-A) from a healthy female Chinese Han.

We obtained skin fibroblasts from a 34-year-old healthy woman and established a human induced pluripotent stem cell (hiPSC) line (INDSUi005-A) using a non-integrated reprogramming approach. The obtained cells have typical characteristics of embryonic stem cells, can express specific pluripotency markers and have the ability to differentiate into three germ layers in vitro. This iPSC cell line can be used as an in vitro model for studying disease mechanisms and developing novel therapies.

DOT1L promotes expression of CD44 through the Wnt/ß-catenin signaling pathway in early gastric carcinoma.

To assess telomere silencing 1-like (DOTIL) gene expression within gastric cancer (GC) tissues as well as its function of promoting cancer stem cell (CSC)-mediated epithelial-mesenchymal switching, tissue samples from 8 patients each in 3 stages (normal, low-grade intraepithelial neoplasia (LGIN), as well as early gastric carcinoma (EGC)) were collected for whole-exome sequencing, which revealed differentially expressed genes (DEGs). The DEGs and their prognostic value were verified through TCGA and GTEx analyses. We also verified the role of DOT1L in EGC development. We collected samples from three patients each with LGIN and EGC for single-cell sequencing. We conducted single-cell transcriptomic analysis, DEG analysis, cell‒cell interaction analysis, and pseudotime analysis using R language. Sites and levels of DOT1L, CD44 and DOT1L expression were verified by IF. We found 703 deleterious mutation sites in the LGIN group and 389 deleterious mutation sites in the EGC group. The LGIN as well as EGC categories exhibited increased levels of DOT1L expression compared to the standard category (P<0.05) in TCGA and GTEx. DOT1L also correlated significantly with TMB (P=8.45E-06), MSI (P=0.001), and tumor proliferation index (P=7.17E-09) in the TCGA and GTEx datasets. In single cells, we found that DOT1L promotes CD44 expression via the Wnt/ß-catenin signaling pathway and the development for stemness properties within GC. In addition, we found that DOT1L, CD44 and CTNNB1 colocalize and correlate positively. In conclusion, one important CSC regulator in GC, DOT1L may be crucial in coordinating the expression of genes specific to a certain lineage during MSC development.

Chronic kidney disease duration and suicide risk among maintenance hemodialysis patients in China.

Background: Our aim was to investigate the relationship between chronic kidney disease (CKD) duration and suicide risk among maintenance hemodialysis patients in China. Methods: Patients with end-stage renal disease (ESRD) who received MHD were enrolled. The demographic and disease characteristics of MHD patients were collected using a self-designed basic information questionnaire. The Suicide Risk Assessment Scale was used to assess suicide risk. Results: A total of 543 (40.8%) patients had suicide risk with Nurses' Global Assessment Scale for Suicide Risk scores ranging from 1 to 19 points. After adjusting for age, gender, disease conditions and mental state, the odds ratios of different CKD duration for suicide risk were 1.00, 2.02, 3.03 and 2.71, respectively (P for trend <.001). There were significant interactions between CKD duration and ESRD duration in relation to suicide risk (P for interaction <.001). There were also interactions between CKD duration and hemodialysis treatment duration, and suicide risk (P for interaction = .01). Patients with ESRD duration of ≤28 months or hemodialysis treatment duration of ≤24 months had the highest risk of suicide when the duration of CKD was 63-94 months, about 2-10 times higher than the other time groups. Conclusions: We found that CKD duration was associated with an increased risk of suicide in maintenance hemodialysis patients in China, independently of other risk factors. Early ESRD and maintenance hemodialysis were associated with suicide in CKD patients.

MOF-derived NiCo hydroxide for highly efficient non-enzymatic glucose biosensing.

An efficient and robust electrocatalyst is significant for glucose biosensing. The emergence of metal-organic framework (MOF) derived materials opens up new avenues for the development of high-performance glucose sensing catalysts. Herein, MOF derived nickel-cobalt hydroxide supported on conductive copper sheet (NiCo-OH/Cu sheet) is prepared at room temperature. The as-obtained NiCo-OH is endowed with three-dimensional network structure which enables the effective exposure of active materials, sufficient contact between glucose molecule and catalyst. The NiCo-OH/Cu sheet is revealed as good glucose electrochemical sensing material with a wide linear range of 0.05∼6.0 mM and a high sensitivity of 1340µA mM-1cm-2. Additionally, the as-fabricated NiCo-OH/Cu sheet displays good anti-interference ability and long-term stability.

Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors.

Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1ß pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold. The biological evaluation identified compound T10, a scaffold hybrid of TNA and salicylic acid, as a potent NLRP3 inflammasome inhibitor. Mechanistically, T10 inhibits the production of ROS and prevents NLRP3 inflammasome-dependent IL-1ß production. In addition, treatment with T10 significantly attenuated inflammatory response in DSS-induced peritonitis. Our work describes a potential tanshinone-based derivative, which needs to be further structurally optimized as NLRP3 inflammasome inhibitors for treating inflammatory disorders.

Morusin suppresses the stemness characteristics of gastric cancer cells induced by hypoxic microenvironment through inhibition of HIF-1α accumulation.

Gastric cancer (GC) is a common, life-threatening malignancy that contributes to the global burden of cancer-related mortality, as conventional therapeutic modalities show limited effects on GC. Hence, it is critical to develop novel agents for GC therapy. Morusin, a typical prenylated flavonoid, possesses antitumor effects against various cancers. The present study aimed to demonstrate the inhibitory effect and mechanism of morusin on the stemness characteristics of human GC in vitro under hypoxia and to explore the potential molecular mechanisms. The effects of morusin on cell proliferation and cancer stem cell-like properties of the human GC cell lines SNU-1 and AGS were assessed by MTT assay, colony formation test, qRT-PCR, flow cytometry analysis, and sphere formation test under hypoxia or normoxia condition through in vitro assays. The potential molecular mechanisms underlying the effects of morusin on the stem-cell-like properties of human GC cells in vitro were investigated by qRT-PCR, western blotting assay, and immunofluorescence assay by evaluating the nuclear translocation and expression level of hypoxia-inducible factor-1α (HIF-1α). The results showed that morusin exerted growth inhibitory effects on SNU-1 and AGS cells under hypoxia in vitro. Moreover, the proportions of CD44+/CD24- cells and the sphere formation ability of SNU-1 and AGS reduced in a dose-dependent manner following morusin treatment. The expression levels of stem cell-related genes, namely Nanog, OCT4, SOX2, and HIF-1α, gradually decreased, and the nuclear translocation of the HIF-1α protein was apparently attenuated. HIF-1α overexpression partially reversed the abovementioned effects of morusin. Taken together, morusin could restrain stemness characteristics of GC cells by inhibiting HIF-1α accumulation and nuclear translocation and could serve as a promising compound for GC treatment.

Engineering of 4-hydroxyphenylacetate 3-hydroxylase derived from Pseudomonas aeruginosa for the ortho-hydroxylation of ferulic acid.

Polyphenolic compounds have natural antioxidant properties, and their antioxidant activity is usually related to the number and position of hydroxyls. Here, we successfully applied the engineered 4-hydroxyphenylacetate 3-hydroxylases (4HPA3Hs) derived from Pseudomonas aeruginosa to catalyze ferulic acid (FA) synthesis of ortho-hydroxyferulic acid (5-hydroxyferulic acid, 5-OHFA). Through optimization of co-expression, the oxygenase component (PaHpaB) and the reductase component (PaHpaC) in E. coli, and optimization of whole-cell catalytic conditions, the engineered strain BC catalyzed ortho-hydroxylation of 2 g/L of FA with a yield of 75 % from 39 %. Through tunnel engineering of PaHpaB, the obtained mutants F301A and Q376A almost completely transformed 2 g/L of FA. Further, a multiple mutant L214A/F301A/Q376A converted 4 g/L FA into 5-OHFA within 12 h, and the yield reached 99.9 %, which was approximately 2.39-fold of the wild type. The kcat/Km value of L214A/F301A/Q376A was about 307 times greater than that of the wide type. Analysis of three-dimensional structural models showed that L214, F301, and Q376 mutated into Ala, which greatly shortened the side chain and broadened the tunnel size, thereby significantly improving the catalytic efficiency of L214A/F301A/Q376A. This biosynthesis of 5-OHFA is simple, efficient, and green, suggesting that it is useful for efficient biosynthesis of polyphenolic compounds.

Biogeographical and biodiversity patterns of planktonic microeukaryotes along the tropical western to eastern Pacific Ocean transect revealed by metabarcoding.

Microeukaryotic plankton (0.2-200 µm), which are morphologically and genetically highly diverse, play a crucial role in ocean productivity and carbon consumption. The Pacific Ocean (PO), one of the world's largest oligotrophic regions, remains largely unexplored in terms of the biogeography and biodiversity of microeukaryotes based on large-scale sampling. We investigated the horizontal distribution of microeukaryotes along a 16,000 km transect from the west to the east of the PO. The alpha diversity indices showed a distinct decreasing trend from west to east, which was highly correlated with water temperature. The microeukaryotic community, which was clustered into the western, central, and eastern PO groups, displayed a significant distance-decay relationship. Syndiniales, a lineage of parasitic dinoflagellates, was ubiquitously distributed along the transect and dominated the community in terms of both sequence and zero-radius operational taxonomic unit (ZOTU) proportions. The prevailing dominance of Syndiniales-affiliated ZOTUs and their close associations with dinoflagellates, diatoms, and radiolarians, as revealed by SparCC correlation analysis, suggested that parasitism may be an important trophic strategy in the surface waters of the PO. Geographical distance and temperature were the most important environmental factors that significantly correlated with community structure. Overall, our study sheds more light on the distribution pattern of both alpha and beta diversities of microeukaryotic communities and highlighted the importance of parasitisms by Syndiniales across the tropical PO.IMPORTANCEUnderstanding the biogeographical and biodiversity patterns of microeukaryotic communities is essential to comprehending their roles in biogeochemical cycling. In this study, planktonic microeukaryotes were collected along a west-to-east Pacific Ocean transect (ca. 16,000 km). Our study revealed that the alpha diversity indices were highly correlated with water temperature, and the microeukaryotic communities displayed a distinct geographical distance-driven pattern. The predominance of the parasitic dinoflagellate lineage Syndiniales and their close relationship with other microeukaryotic groups suggest that parasitism may be a crucial survival strategy for microeukaryotes in the surface waters of the Pacific Ocean. Our findings expand our understanding of the biodiversity and biogeographical pattern of microeukaryotes and highlight the significance of parasitic Syndiniales in the surface ocean.

Yield stress Measurement of municipal sludge: A comprehensive evaluation of testing methods and concentration effects using a rotational rheometer.

Accurate prediction and measurement of yield stress are crucial for optimizing sludge treatment and disposal. However, the differences and applicability of various methods for measuring yield stress are subjects of ongoing debate. Meanwhile, literature on measuring sludge yield stress is limited to low solid concentrations (TS <10%), understanding and studying the yield stress of medium to high solid concentration sludge is crucial due to increasingly stringent standards for sludge treatment and disposal. So, this study employed a rotational rheometer to measure sludge yield stress across a wide range of TS (4-50%) using steady shear, dynamic oscillatory shear, and transient shear. The study derived significant conclusions by comparing and summarizing the applicability and limitations of each testing method: Dynamic oscillatory shear methods, including G'-σ curve method, γ-σ curve method, and G**γc method can measure sludge yield stress ranging from 4% to 40% TS, while other methods are restricted to low or limited solid concentrations; The G' = G″ method, utilizing the intersection of G' and G″ curves, consistently yields the highest value for yield stress when 4%≤ TS ≤ 12%; The rotational rheometer cannot measure sludge yield stress when the solid concentration exceeds 40% TS; The relationship between sludge yield stress and solid concentration is stronger as a power-law for TS ≤ 25%, transitioning to linear for higher concentrations (28%≤ TS <40%). This study systematically explores the applicability and limitations of various measurement methods for characterizing sludge yield stress across a wide range of solid concentrations, providing valuable guidance for scientific measurement and highlighting challenging research issues.

Risk and Incidence of Cardiovascular Disease Associated with Polycystic Ovary Syndrome.

AIMS: We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD. METHODS: We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. Global incidence of PCOS-associated CVD was calculated by a population attributable fraction (PAF) modelling using the pooled RR, PCOS prevalence, CVD incidence number and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. RESULTS: The risk of CVD was significantly increased in the women with PCOS for all-age group (pooled RR 1.51, 95% CI 1.36-1.69), and 10- to 54-year-old (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS associated CVD cases in women across all-age group has rised from 102 530 to 235 560. The most affected regions were East Asia & Pacific (108 430, 66 090-166 150) in 2019. The South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%; 0.41-0.56) is faster than that of the all-age group (0.34; 0.27-0.42). The middle- or low-middle sociodemographic index countries, experienced higher increase trend of CVD due to PCOS in the past thirty years. CONCLUSIONS: Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with high PCOS-associated CVD burden, especially premature CVD in women under 55 years.

Studies have reported cardiovascular disease (CVD) is the leading cause of mortality for women. Meanwhile, women with polycystic ovary syndrome (PCOS) substantially elevate the risk of CVD. However, no studies have quantified the impact of PCOS on the overall CVD burden. This study performed a meta-analysis to assess the risk of CVD in all-age group and 10 to 54 years old women, living with PCOS with 17 articles, and estimated the burdens of PCOS-associated CVD burden, by global, 7 World-bank defined regions, and 204 countries, from 1990 to 2019, using a PAF modelling. Our study implicated women in all-age group, and 10 to 54 years old with PCOS face a 1.51-fold, and 1.37-fold increased risk of CVD compared those without, respectively. Globally, approximately 0.85% of CVD new cases in 2019 were associated with PCOS, corresponded a more than 2-fold increase of PCOS-associated CVD cases from 1990. However, the burden of PCOS-associated CVD varies widely by region; for instance, nearly 1.49% of CVD new cases were attributed to PCOS in North America. Meanwhile, the East Asia & Pacific region had the highest PCOS-associated new CVD case, and the South Asia experienced the highest increase in age-standardised incidence rates of CVD due to PCOS. Notably, we found higher worldwide PAFs, and annual increase ASIR than that in all-age group women. This result suggests that premature CVD in women with PCOS under 55 years deserve more attention.

A MOF-derived flower-shaped CeCo-oxide as a multifunctional material for high-performance lithium-ion batteries and supercapacitors.

Precursor method is a well-known technology for preparing certain functional materials. In this work, a novel 3d-4f bimetallic organic framework, denoted as 45MCeCo (45 M representing 4,5-imidazole dicarboxylic acid), was successfully synthesized via a hydrothermal technique. The compound thus obtained has the molecular formula of C10H11CeCoN4O12. By meticulously controlling the amounts of the experimental materials, it was feasible to prepare flower-like crystals possessing identical single crystal structures and significantly larger specific surface areas. As a precursor for electrode materials, this structure underwent calcination at different temperatures to prepare Co3O4/CeO2 composites with in situ composite heterostructures. Post-electrochemical tests revealed that CeO2 remains unreactive across all potentials, thereby contributing to the stabilization of the electrode material structure. In contrast, Co3O4 participated in redox reactions to provide a specific capacity to the sample. In addition, when comparing the performance of the electrode material under different calcination conditions, it became evident that the material exhibited optimal electrochemical performance when subjected to a temperature of 700 °C for 2 h.

Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, is often diagnosed at an advanced stage. Surgical interventions are often ineffective, leading HCC patients to rely on systemic chemotherapy. Unfortunately, commonly used chemotherapeutic drugs have limited efficacy and can adversely affect vital organs, causing significant physical and psychological distress for patients. Natural medicine monomers (NMMs) have shown promising efficacy and safety profiles in HCC treatment, garnering attention from researchers. In recent years, the development of novel targeted drug delivery systems (TDDS) combining NMMs with nanocarriers has emerged. These TDDS aim to concentrate drugs effectively in HCC cells by manipulating the characteristics of nanomedicines, leveraging receptor and ligand interactions, and utilizing endogenous stimulatory responses to promote specific nanomedicines distribution. This comprehensive review presents recent research on TDDS for HCC treatment using NMMs from three perspectives: passive TDDS, active TDDS, and stimuli-responsive drug delivery systems (SDDS). It consolidates the current state of research on TDDS for HCC treatment with NMMs and highlights the potential of these innovative approaches in improving treatment outcomes. Moreover, the review also identifies research gaps in the related fields to provide references for future targeted therapy research in HCC.

Targeting the NLRP3 inflammasome in psoriasis.

The NLRP3 inflammasome, a complex consisting of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3, has emerged as a critical mediator of pathological inflammation and a significant therapeutic target for various inflammatory diseases. Psoriasis, a chronic inflammatory skin condition without a definitive cure, has shown promising results in animal models through the inhibition of the NLRP3 inflammasome. This review aims to explore the development of the NLRP3 inflammasome in psoriasis and the molecular mechanisms responsible for its inhibition by natural products and small molecules currently being developed for psoriasis treatment. Furthermore, we are examining clinical trials using agents that block the NLRP3 pathway for the treatment of psoriasis. This study is timely to provide a new perspective on managing psoriasis.

Scalable, Green, Flexible Photochromic Bacterial Cellulose for Multicolor Switching, Photo-patterning, and Daily Sunlight UV Monitoring.

Sustainable, durable, and diverse photochromic smart textiles based on bacterial cellulose (BC) have emerged as attractive candidates in UV-sensing applications due to the green and easy functionalization of BC. However, existing BC-based photochromic textiles lack photochromic efficiency and combining fastness. In this study, a green strategy for in situ fermentation is developed to achieve the directional distribution of functional particles and remarkable photochromism in photochromic bacterial cellulose (PBC). The unique functional design obtained by regulating the photochromic dye distribution in 3D nanonetworks of PBCs during in situ growth affords a more uniform distribution and high fastness. Benefiting from the uniform distribution of photochromic dyes and adequate utilization of the 3D network structure, more surface area is provided to receive and utilize the photon energy from the UV rays, making the photochromic process more effective. The as-prepared PBCs exhibited rapid (within 1 min) and stable (30 cycles) discoloration and multicolor selectivity. Their simple preparation process and exceptional wearability, e.g., their flexibility, lightweight, and air permeability, make them suitable for various applications, including tunable color switching systems, photopatterning, and daily sunlight UV monitoring. This study provides empirical value for the biofabrication of photochromic textiles and wearable flexible UV sensors.