Overexpressed Poldip2 incurs retinal fibrosis via the TGFß1/SMAD3 signaling pathway in diabetic retinopathy.

Retinal fibrosis is one of the major features of Diabetic retinopathy. Our recent research has shown that Poldip2 can affect early DR through oxidative stress, but whether or not Poldip2 would regulate retinal fibrosis during DR development is still enigmatic. Here, Diabetic Sprague-Dawley (SD) rats were induced with STZ and treated with AAV9-Poldip2shRNA, while human retinal pigment epithelial cells (ARPE-19) were treated with high glucose (HG) or Poldip2 siRNA. We identified that in STZ-induced DR rats and ARPE-19 treated with high glucose, the expression of Poldip2, TGFß1, P-SMAD3/SMAD3, MMP9, COL-1, FN, and CTGF increased while the expression of Cadherin decreased. However, deleting Poldip2 inhibited the TGF-ß1/SMAD3 signaling pathway and attenuated the above protein expression in vivo and in vitro. Mechanistically, we found that Poldip2 promotes the activation of SMAD3, and facilitates its nuclear translocation through interacting with it, and significantly enhances the expression of fibrosis makers. Collectively, it was identified that Poldip2 is a novel regulator of DR fibrosis and it is expected to become a therapeutic target for PDR.

Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study.

OBJECTIVE: To evaluate the trends and cross-country inequalities of global osteoarthritis (OA) burden over the last 30 years, and further predicted its changes to 2035. METHODS: The estimates and 95 % uncertainty intervals (UIs) for incidence, prevalence, and disability-adjusted life-years (DALYs) of OA were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We described OA epidemiology at global, regional, and national levels, analyzed 1990-2019 trends in OA burden from overall, local, and multi-dimension scopes, decomposed OA burden according to population size, age structure, and epidemiologic changes, quantified cross-country inequalities in OA burden using standard health equity methods recommended by World Health Organization, and predicted changes of OA burden to 2035. RESULTS: GBD 2019 estimated 527,811,871 (95 % UIs: 478,667,549 to 584,793,491) prevalent cases, 41,467,542 (95 % UIs: 36,875,471 to 46,438,409) incident cases and 18,948,965 (95 % UIs: 9,571,298 to 37,659,660) DALYs cases of OA worldwide in 2019, with the highest cases in East Asia and highest age-standardized rate (ASR) in high-income North America. The global burden of OA increased overall from 1990 to 2019 with the fastest growth observed in the first decade of the 21st century. Decomposition analysis revealed that OA knee (62.78 %), women (60.47 %), and middle sociodemographic index (SDI) quintile (32.35 %) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. A significant increase in SDI-related inequalities was detected, and the gap in DALYs between the highest SDI country and the lowest SDI country increased from 179.5 [95 % confidence interval (CI): 149.3-209.8] per 100,000 in 1990 to 341.9 (95 % CI: 309.5-374.4) per 100,000 in 2019. Notably, although the ASR of incidence, prevalence, and DALYs of OA was predicted to decrease annually from 2020 to 2035, the case number of these metrics was predicted to keeping increasing, with predicted values of 52,870,737 [95 % credible interval (Crl): 39,330,063 to 66,411,411], 727,532,373 (95 % Crl: 542,765,783 to 912,298,962), and 25,986,983 (95 % Crl: 19,216,928 to 32,757,038) in 2035, respectively. CONCLUSIONS: As a major public health issue, the global burden of OA showed an overall increasing trend from 1990 to 2019, which was primarily driven by population growth and aging. Countries with high SDI shouldered disproportionately high OA burden, and the SDI-related inequalities across countries exacerbated over time. This study highlighted great challenges in the control and management of OA, including both growing case number and distributive inequalities worldwide, which may be instructive for better making public health policy and reasonably allocating medical source.

Shared and task-specific brain functional differences across multiple tasks in children with developmental dyslexia.

Different tasks have been used in examining the neural functional differences associated with developmental dyslexia (DD), and consequently, different findings have been reported. However, very few studies have systematically compared multiple tasks in understanding what specific task differences each brain region is associated with. In this study, we employed an auditory rhyming task, a visual rhyming task, and a visual spelling task, in order to investigate shared and task-specific neural differences in Chinese children with DD. First, we found that children with DD had reduced activation in the opercular part of the left inferior frontal gyrus (IFG) only in the two rhyming tasks, suggesting impaired phonological analysis. Children with DD showed functional differences in the right lingual gyrus/inferior occipital gyrus only in the two visual tasks, suggesting deficiency in their visuo-orthographic processing. Moreover, children with DD showed reduced activation in the left dorsal inferior frontal gyrus and increased activation in the right precentral gyrus across all of the three tasks, suggesting neural signatures of DD in Chinese. In summary, our study successfully separated brain regions associated with differences in orthographic processing, phonological processing, and general lexical processing in DD. It advances our understanding about the neural mechanisms of DD.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis.

Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood-retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

A Benzothiadiazole-Based Zn(II) Metal-Organic Framework with Visual Turn-On Sensing for Anthrax Biomarker and Theoretical Calculation.

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Coumarin-Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis.

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

Unraveling the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in aqueous host-guest complexation.

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.

The multifaceted role of RNA-based regulation in plant stress memory.

Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.

Blue ZnSeTe quantum dot light-emitting diodes with low efficiency roll-off enabled by an in situ hybridization of ZnMgO nanoparticles and amino alcohol molecules.

ZnSeTe quantum dots (QDs) have been employed as promising emitters for blue QD-based light-emitting diodes (QLEDs) due to their unique optoelectronic properties and environmental friendliness. However, such QLEDs usually suffer from serious efficiency roll-off primarily stemming from exciton loss at the interface of the QD layer and the ZnMgO (ZMO) electron transport layer (ETL), which remarkably hinders their application in flat-panel displays. Herein, we propose an in situ hybridization strategy that involves the pre-introduction of amino alcohols into the reaction solution. This strategy effectively suppresses the nucleophilic condensation process by facilitating the coordination of ammonium and hydroxyl groups with metal cations (M2+, i.e. Zn2+ and Mg2+). It slows down the growth rate of ZMO nanoparticles (NPs) while simultaneously facilitating M-O coordination, resulting in the synthesis of small-sized and low-defect ZMO NPs. Notably, this in situ hybridization approach not only alleviates emission quenching at the QDs/ETL interface but also elevates the energy level of the ETL for enhancing carrier injection. We further investigated the impact of amino alcohols with varying carbon-chain lengths on the performance of ZMO NPs and the corresponding LED devices. The optimal blue ZnSeTe QLED demonstrates an impressive EQE of 8.6% with only an ∼11% drop when the current density is increased to 200 mA cm-2, and the device operating lifetime extends to over 1300 h. Conversely, the device utilizing traditionally post-treated ZMO NPs as the ETL exhibits 45% efficiency roll-off and device lifetime of merely 190 h.

New anti-inflammatory limonoids from the fruits of Melia azedarach.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

High-Efficiency and Stable Colloidal One-Dimensional Core/Shell Nanorod Light-Emitting Diodes.

Anisotropic nanocrystals such as nanorods (NRs) display unique linearly polarized emission, which is expected to break the external quantum efficiency (EQE) limit of quantum dot-based light-emitting diodes (LEDs). However, the progress in achieving a higher EQE using NRs encounters several challenges, primarily involving a low photoluminescence quantum yield (PLQY) of NRs and imbalanced charge injection in NR-LEDs. In this work, we investigated NR-LEDs based on CdSe/CdZnS/ZnS rod-in-rod NRs with a high PLQY and higher linear polarization compared to those of dot-in-rod NRs. The balanced charge injection is achieved using ZnMgO nanoparticles as the electron transport layer and poly-TPD {poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)benzidine]} as the hole transport layer. Therefore, the NR-LEDs exhibit a maximum EQE of 21.5% and a maximum luminance of >120 000 cd/m2 owing to the high level of in-plane transitions with a dipole moment of 90%. The NR-LEDs also have greatly inhibited droop in EQE under a high current density as well as outstanding operation lifetime and cycle stability.

Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409.

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3-10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p = 0.008). Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

Recent Advances in the Application of P(III)-Nucleophiles to Create New P-C Bonds through Michaelis-Arbuzov-Type Rearrangement.

Organophosphorus compounds have long been considered valuable in both organic synthesis and life science. P(III)-nucleophiles, such as phosphites, phosphonites, and diaryl/alkyl phosphines, are particularly noteworthy as phosphorylation reagents for their ability to form new P-C bonds, producing more stable, ecofriendly, and cost-effective organophosphorus compounds. These nucleophiles follow similar phosphorylation routes as in the functionalization of P-H bonds and P-OH bonds. Activation can occur through photocatalytic, electrocatalytic, or thermo-driven reactions, often in coordination with a Michaelis-Arbuzov-trpe rearrangement process, to produce the desired products. As such, this review offers a thorough overview of the phosphorylated transformation and potential mechanisms of P(III)-nucleophiles, specifically focusing on developments since 2010. Notably, this review may provide researchers with valuable insights into designing and synthesizing functionalized organophosphorus compounds from P(III)-nucleophiles, guiding future advancements in both research and practical applications.

Zn-Catalyzed Dehydroxylative Phosphorylation of Allylic Alcohols with P(III)-Nucleophiles.

A novel and efficient protocol for the synthesis of diarylallyl-functionalized phosphonates, phosphinates, and phosphine oxides through the zinc-catalyzed dehydroxylative phosphorylation of allylic alcohols with P(III)-nucleophiles via a Michaelis-Arbuzov-type rearrangement is reported. A broad range of allylic alcohols and P(III)-nucleophiles (P(OR)3, ArP(OR)2, and Ar2P(OR)) are well tolerated in this reaction, and the expected dehydroxylative phosphorylation products could be synthesized with good to excellent yields under the optimal reaction conditions. The reaction can be easily scaled up at a gram-synthesis level. Furthermore, through the step-by-step control experiments, kinetic study experiments, and 31P NMR tracking experiments, we acquired insights into the reaction and proposed the possible mechanism for this transformation.