The first ER-targeting flavone-based fluorescent probe for Cys: Applications in real-time tracking in an epilepsy model and food analysis.

Epilepsy is one of the most commonly-seen neurological disorders, and both endoplasmic reticulum stress (ERS) and oxidative stress (OS) have been demonstrated to be associated with epileptic seizures. As one of the three endogenous thiol-containing amino acids, cysteine (Cys) is recognized not only as an important biomarker of various biological processes but also widely used as a significant additive in the food industry. However, the exact role that Cys plays in ERS has not been well answered up to now. In this paper, we reported the first flavone-based fluorescent probe (namely BFC) with nice endoplasmic reticulum (ER)-targeting ability, which was capable of monitoring Cys in a fast response (3.0 min), large stokes shift (130 nm) and low detection limit (10.4 nM). The recognition mechanism of Cys could be attributed to the addition-cyclization reaction involving a Cys residue and an acrylate group, resulting in the release of the strong excited-state intramolecular proton transfer (ESIPT) emission molecule of benzoflavonol (BF). The low cytotoxicity and good biocompatibility of the probe BFC allowed for monitoring the fluctuation of endogenous Cys levels under both ERS and OS processes, as well as in zebrafish models of epilepsy. Quantitative determination of Cys with the probe BFC was also achieved in three different food samples. Additionally, a probe-immersed test strips integrated with a smartphone device was successfully constructed for on-site colorimetric detection of Cys. Undoubtedly, our work provided a valuable tool for tracking Cys levels in both an epilepsy model and real food samples.

Identification of Primary Organophosphate Esters Contributing to Enhanced Risk of Gestational Diabetes Mellitus Based on a Case-Control Study.

Epidemiological studies on associations of organophosphate ester (OPE) exposure and gestational diabetes mellitus (GDM) risk, which remain rare and inconclusive, were carried out with a case-control population comprising 287 GDM and 313 non-GDM pregnant women recruited from Tianjin. The GDM group suffered distinctly higher serum concentrations of tri-n-butyl phosphate (TNBP), tri(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), tri-iso-propyl phosphate (TIPP), and tri(1-chloro-2-propyl) phosphate (TCIPP) than the healthy control group (p < 0.001). Traditional analysis methods employed for either individual or mixture effects found positive correlations (p < 0.05) between the concentrations of five OPEs (i.e., TNBP, TBOEP, TPHP, TIPP, and TCIPP) and the incidence of GDM, while 2-ethylhexyl diphenyl phosphate, tri(1-chloro-2-propyl) phosphate, and bis(2-ethylhexyl) phosphate exhibited opposite effects. Three machine learning methods considering the concurrence of OPE mixture exposure and population characteristics were applied to clarify their relative importance to GDM risk, among which random forest performed the best. Several OPEs, particularly TNBP and TBOEP ranking at the top, made greater contributions than some demographical characteristics, such as prepregnancy body mass index and family history of diabetes, to the occurrence of GDM. This was further validated by another independent case-control population obtained from Hangzhou.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent.

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing-antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

The Role of Platelet Distribution Width in the Association Between Blood Glucose and Neurological Impairment Severity in Acute Ischemic Stroke: A Moderated Mediation Model.

Objective: Fasting blood glucose (FBG) is a recognized risk factor for Ischemic Stroke, but little research has examined the interaction among FBG, Platelet Distribution Width (PDW) and the severity of neuronal damage. Thus, the present study constructs a moderated mediation model aimed to elucidate the relationships among FBG, PDW, and NIHSS scores in patients with acute ischemic stroke (AIS). Methods: We conducted a cross-sectional study on 431 AIS patients. Upon hospital admission, we assessed the patients' NIHSS scores and collected blood samples to measure FBG and PDW levels. The relationship between FBG and NIHSS scores moderated by PDW was analyzed by linear curve fitting analysis, multiple linear regression analysis, and moderated mediation analysis respectively. Results: In the tertile grouping based on FBG, both PDW and NIHSS scores of AIS patients demonstrated an increase corresponding with rising levels of FBG (p<0.001 for both). Multiple linear regression analysis revealed that, the ß coefficients (95% CI) for the relationship between FBG and NIHSS scores were 1.49 (1.27-1.71, p<0.01) post-adjustment for potential confounders. The ß coefficients (95% CI) for the relationship between FBG and PDW were 0.02 (0.01-0.04, p<0.01) post-adjustment. Likewise, for the relationship between PDW and NIHSS scores, the ß coefficients (95% CI) were 4.33 (3.07-5.59, p<0.01) after adjustment. These positive association remained consistent in sensitivity analysis and hierarchical analysis. Smoothed plots suggested that there are linear relationships between FBG and PDW and NIHSS scores respectively. Further mediation analysis indicated that increased PDW significantly (p<0.01) mediated 5.91% of FBG-associated increased NIHSS scores. Conclusion: This study suggested that FBG levels were associated with NIHSS scores, and the FBG-associated neurological impairment may be partially mediated by PDW. These findings underscore the importance of monitoring FBG and PDW levels in AIS patients, potentially guiding risk intervention strategies.

Epstein Barr virus infection induces tissue-resident memory T cells in mucosal lymphoid tissues.

Epstein Barr virus (EBV) contributes to around 2% of all tumors worldwide. Simultaneously, more than 90% of healthy human adults persistently carry EBV without clinical symptoms. In most EBV carriers it is thought that virus-induced tumorigenesis is prevented by cell-mediated immunity. Specifically, memory CD8+ T cells recognize EBV-infected cells during latent and lytic infection. Using a symptomatic primary infection model, similar to infectious mononucleosis (IM), we found EBV-induced CD8+ tissue-resident memory T cells (TRMs) in mice with a humanized immune system. These human TRMs were preferentially established after intranasal EBV infection in nasal-associated lymphoid tissues (NALT), equivalent to tonsils, the primary site of EBV infection in humans. They expressed canonical TRM markers, including CD69, CD103, and BLIMP-1, as well as Granzyme B, CD107a and CCL5. Despite cytotoxic activity and cytokine production ex vivo, these TRMs demonstrated reduced CD27 expression and proliferation and failed to control EBV viral loads in the NALT during infection although effector memory T cells (TEMs) controlled viral titers in spleen and blood. Overall, TRMs are established in mucosal lymphoid tissues by EBV infection, but primarily systemic CD8+ T cell expansion seems to control viral loads in the context of IM-like infection.

Conformational change-based fluorometric aptasensor for sensitive cadmium(II) detection in fruits and vegetables.

Cadmium (Cd2+) is a highly toxic heavy metal that can accumulate in the human body through contaminated food and water, posing great health risks. In this study, a label-free fluorescent aptasensor based on SYBR Green I (SGI) for the rapid and sensitive detection of Cd2+ in food samples was designed. The aptasensor utilizes a Cd2+-specific aptamer (Cd-(21)) and its complementary strand (CSCd-(21)) to form a double-stranded DNA (dsDNA) structure in the absence of Cd2+. SGI intercalates into the dsDNA, resulting in a strong fluorescence signal. In the presence of Cd2+, the aptamer undergoes a conformational change, preventing the formation of dsDNA and leading to a decrease in fluorescence intensity. Under optimized conditions, the aptasensor exhibited a linear response to Cd2+ concentrations ranging from 0.11 to 157.37 ng mL-1, with a limit of detection (LOD) of 0.07 ng mL-1. The aptasensor demonstrated high specificity and was successfully applied to detect Cd2+ in fruits and vegetables, with satisfactory recovery rates (95-111%). The proposed aptasensor provides a promising tool for the rapid and sensitive detection of Cd2+ in food.

Spatiotemporal evolution of runoff and sediment and their dominant driving factors in the Lower Jinsha River basin.

The Jinsha River Basin (JRB) contributes a significant amount of sediment to the Yangtze River; however, an imbalance exists between runoff and sediment. The underlying mechanisms and primary factors driving this imbalance remain unclear. In this study, the Shapley Additive Explanation (SHAP) and Geographical Detector Model (GDM) were employed to quantify the importance of the driving factors for water yield (WYLD) and sediment yield (SYLD) using the Soil and Water Assessment Tool (SWAT) model in the JRB. The results indicated that the SWAT model performed well in simulating runoff and sediment, with R2 > 0.61 and NSE > 0.5. Based on the simulated data, SYLD exhibited strong spatiotemporal linkages with WYLD. Temporally, both sediment and runoff showed decreasing trends, with the sediment decrease being more pronounced. Spatially, WYLD and SYLD displayed similar distribution patterns, with low values in the southwest and high values in the northeast. By quantifying the driving factors, we found that climatic factors, including precipitation and potential evapotranspiration, were the main influencing factors for WYLD and SYLD across the entire region, though their contributions to the two variables differed. For WYLD, climatic factors accounted for 70 % of the total influencing factors, whereas their contribution to SYLD was 50 %. Furthermore, soil type and land-use type played significant roles in the SYLD, with importance values of 16 % and 12 %, respectively. Under the influence of surface conditions, the proportion of SYLD in the JRB to the total SYLD in the Yangtze River Basin was greater than that of WYLD. The findings of this study provide scientific evidence and technical support for local environmental impact assessments and the formulation of soil and water conservation plans.

Bacteria modulate microalgal aging physiology through the induction of extracellular vesicle production to remove harmful metabolites.

The bloom and bust patterns of microalgae in aquatic systems contribute massively to global biogeochemical cycles. The decline of algal blooms is mainly caused by nutrient limitation resulting in cell death, the arrest of cell division and the aging of surviving cells. Nutrient intake can re-initiate proliferation, but the processes involved are poorly understood. Here we characterize how the bloom-forming diatom Coscinodiscus radiatus recovers from starvation after nutrient influx. Rejuvenation is mediated by extracellular vesicles that shuttle reactive oxygen species, oxylipins and other harmful metabolites out of the old cells, thereby re-enabling their proliferation. By administering nutrient pulses to aged cells and metabolomic monitoring of the response, we show that regulated pathways are centred around the methionine cycle in C. radiatus. Co-incubation experiments show that bacteria mediate aging processes and trigger vesicle production using chemical signalling. This work opens new perspectives on cellular aging and rejuvenation in complex microbial communities.

Natural harmaline acts as novel fluorescent probe for hypochlorous acid and promising therapeutic candidate for rheumatoid arthritis.

Endogenous hypochlorous acid (HOCl) is one of the most important reactive oxygen species (ROS) and acts as a distinct biomarker that is involved in various inflammatory responses including rheumatoid arthritis (RA). Therefore, it's crucial to develop an efficient method for the tracking and analysis of HOCl levels in vivo. Natural products continue to be compounds of interest, because they not only offer diverse and specific molecular scaffolds but also provide invaluable sources for new drug discovery. Herein, we firstly demonstrated harmaline (HML), a natural alkaloid mainly found in Peganum harmala L, could be acted as a novel fluorescent probe for HOCl with exceptional precision and responsiveness. Remarkably, this probe not only specifically tracked HOCl levels in cells and inflammatory RA mouse models, but also exhibited effective anti-inflammatory effects on RAW264.7 cells and anti-proliferative effects on fibroblast-like synoviocytes. Furthermore, HML has the potential to alleviate LPS-induced inflammation by inhibiting the NF-κB signaling pathway. This study represents the first example of a natural product that can simultaneously act as a fluorescent probe for specific ROS and a promising therapeutic candidate for a specific disease, which will undoubtedly extend the application of fluorophore-rich natural products.

Recent advances in virulence of a broad host range plant pathogen Sclerotinia sclerotiorum: a mini-review.

Sclerotinia sclerotiorum is a typical necrotrophic plant pathogenic fungus, which has a wide host range and can cause a variety of diseases, leading to serious loss of agricultural production around the world. It is difficult to control and completely eliminate the characteristics, chemical control methods is not ideal. Therefore, it is very important to know the pathogenic mechanism of S. sclerotiorum for improving host living environment, relieving agricultural pressure and promoting economic development. In this paper, the life cycle of S. sclerotiorum is introduced to understand the whole process of S. sclerotiorum infection. Through the analysis of the pathogenic mechanism, this paper summarized the reported content, mainly focused on the oxalic acid, cell wall degrading enzyme and effector protein in the process of infection and its mechanism. Besides, recent studies reported virulence-related genes in S. sclerotiorum have been summarized in the paper. According to analysis, those genes were related to the growth and development of the hypha and appressorium, the signaling and regulatory factors of S. sclerotiorum and so on, to further influence the ability to infect the host critically. The application of host-induced gene silencing (HIGS)is considered as a potential effective tool to control various fungi in crops, which provides an important reference for the study of pathogenesis and green control of S. sclerotiorum.

Aptamer-functionalized triptolide with release controllability as a promising targeted therapy against triple-negative breast cancer.

Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Combined traditional Chinese medicine therapy for the treatment of infertility with polycystic ovary syndrome: A network meta-analysis of randomized controlled trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.

Telomere-to-telomere Citrullus super-pangenome provides direction for watermelon breeding.

To decipher the genetic diversity within the cucurbit genus Citrullus, we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus. The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus, suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.

A novel AIE-based mitochondria-targeting fluorescent probe for monitoring of the fluctuation of endogenous hypochlorous acid in ferroptosis models.

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis.

Widely targeted metabolomics and flavoromics reveal the effect of Wickerhamomyces anomalus fermentation on the volatile and nonvolatile metabolites of black garlic juice.

Black garlic has a variety of biological activities, but many consumers cannot accept it because of the garlic odor and the bitter taste. In this study, fermentation with yeast Wickerhamomyces anomalus was adopted to improve the flavor of black garlic juice. Although fermentation reduced antioxidant activities, the garlicky odor and bitter taste were weakened. Metabolomic analysis revealed 141 metabolites were significantly differentially regulated. The upregulated metabolites were mainly related to nucleotides, organic acids and their derivatives, while the downregulated metabolites were mainly related to amino acids, lipids and their derivatives. Flavoromics analysis revealed that 137 metabolites were significantly differentially regulated, particularly garlicky and pungent volatiles were significantly downregulated. Correlation analysis indicated that esters are most closely related to nonvolatile metabolites, and lipids degradation was significantly correlated with volatiles. The results indicated that W. anomalus fermentation is an effective strategy to improve the flavor of black garlic juice.

A novel LD-targeting cysteine-activated fluorescent probe for diagnosis of APAP-induced liver injury and its application in food analysis.

Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys.

Effects of Foliar Spraying of Dicarboxylicdimethylammonium Chloride on Cadmium and Arsenic Accumulation in Rice Grains.

A field experiment with double cropping rice was carried out to study the foliar application effects of dicarboxylicdimethylammonium chloride (DDAC) on cadmium (Cd) and arsenic (As) accumulation in rice grains. The results showed that the spraying of DDAC could significantly reduce the accumulation of Cd and As in rice grains. The highest reductions in Cd and As content were observed when 1.5 mmol L-1 DDAC was sprayed, with 49.1% and 27.4% reductions in Cd and As content in early rice grains and 56.5% and 28.1% reductions in Cd and As content in late rice grains, respectively. In addition, the content of calcium (Ca) in rice grains increased significantly after DDAC foliar application, which was also conducive to the synthesis of amino acids such as glutamate (Glu), glycine (Gly) and cysteine (Cys) in rice grains. The results indicated that the foliar spraying of DDAC can inhibit the absorption, transport, accumulation and toxicity of Cd and As in rice grains by increasing amino acid synthesis and regulating the absorption and transport of essential elements.

Citric Acid Inhibits Cd Absorption and Transportation by Improving the Antagonism of Essential Elements in Rice Organs.

Excessive cadmium (Cd) in rice is a global environmental problem. Therefore, reducing Cd content in rice is of great significance for ensuring food security and human health. A field experiment was conducted to study the effects of foliar application of citric acid (CA) on Cd absorption and transportation in rice under high Cd-contaminated soils (2.04 mg·kg-1). This study revealed that there was a negative correlation between Cd content in vegetative organs and CA content, and that foliar spraying of CA (1 mM and 5 mM) significantly increased CA content and reduced Cd content in vegetative organs. The Cd reduction effect of 5 mM CA was better than that of 1 mM, and 5 mM CA reduced Cd content in grains and spikes by 52% and 37%, respectively. CA significantly increased Mn content in vegetative organs and increased Ca/Mn ratios in spikes, flag leaves, and roots. CA significantly reduced soluble Cd content in vegetative organs and promoted the transformation of Cd into insoluble Cd, thus inhibiting the transport of Cd from vegetative organs to grains. The foliar field application of 1 mM and 5 mM CA could inhibit Cd absorption and transportation by reducing Cd bioactivity and increasing the antagonistic of essential elements in rice vegetative organs. These results provide technical support and a theoretical basis for solving the problem of excessive Cd in rice.

Metal-organic framework (MOF)-based materials for pyroptosis-mediated cancer therapy.

Pyroptosis is regarded as a promising strategy to modulate tumor immune microenvironments for anticancer therapy. Although pyroptosis inducers have been extensively explored in the biomedical field, their drug resistance, off-targeting capacity, and adverse effects do not fulfill the growing demands of therapy. Nowadays, metal-organic frameworks (MOFs) with unique structures and facile synthesis/functionalization characteristics have shown great potential in anticancer therapy. The flexible choices of metal ions and ligands endow MOFs with inherent anti-cancer efficiency, whereas the porous structures in MOFs make them ideal vehicles for delivering various chemodrug-based pyroptosis inducers. In this review, we provide the latest advances in MOF-based materials to evoke pyroptosis and give a brief but comprehensive review of the different types of MOFs for pyroptosis-mediated cancer therapy. Finally, we also discuss the current challenges of MOF-based pyroptosis inducers and their future prospects in this field.

Associations of short-term changes in obesity indices with all-cause mortality and cardiovascular disease.

OBJECTIVE: This study aimed to investigate how short-term changes (1-, 3-, and 5-year) in obesity measures affect mortality and cardiovascular disease (CVD) risk. METHODS: We analyzed longitudinal data from the MJ Health Centre (n = 43,304 for the 1-year study; 24,295 for the 3-year study; 16,138 for the 5-year study) with median follow-up periods of 15.8, 13.9, and 12.3 years, respectively. Associations of short-term obesity indices changes with mortality and Framingham Risk Score changes were explored using time-dependent coefficient Cox regression models, restricted cubic splines, and multivariable linear regression models. RESULTS: All-cause mortality was negatively associated with short-term weight and BMI changes, with greater reductions causing poorer outcomes. Compared with stable groups, short-term reduced weight and BMI were associated with greater risks of all-cause mortality and CVD-specific mortality (5-year study only). Also, either 1- and 3-year reduced or 3-year increased waist circumference and waist to height ratio were related to higher all-cause and CVD deaths than stable groups, respectively. Nonlinear relationships indicated lower cutoff values for short-term changes in obesity indices in predicting all-cause mortality. Decreased obesity indices significantly improved CVD profiles. CONCLUSIONS: Short-term changes in obesity indices show complex mortality risks, urging personalized approaches beyond a simple weight loss focus.