A novel concern from two sample Mendelian randomization study: The effects of air pollution exposure on the cardiovascular, respiratory, and nervous system.

BACKGROUND: Cardiovascular, respiratory, and nervous system diseases have high morbidity and mortality rates, but the causal relationship between air pollution and these diseases remains controversial. METHODS: We conducted a large-scale genome-wide association (GWAS) study using Mendelian randomization (MR) to investigate the association between air pollution like Nitrogen dioxide (NO2), Nitrogen oxides (NOX), Particulate matter with diameter<2.5µm (PM2.5), Particulate matter with diameter<10µm (PM10) and cardiovascular, respiratory, and nervous system diseases, including acute myocardial infarction, heart failure, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, stroke and Parkinson's disease. This study included 337,199 patients with acute myocardial infarction, 178,726 patients with heart failure, 463,010 patients with asthma, 462,933 patients with COPD, 486,484 patients with pneumonia, 484,598 patients with stroke, and 482,730 patients with Parkinson's disease. All genetic tools were identified from GWAS. The association effects of environmental pollution and these diseases were investigated using MR analysis, sensitivity analysis with heterogeneity, pleiotropy test, and leave-one-out test. RESULTS: Our MR analysis showed the association between NOX and the development of COPD and stroke (Odds ratio (OR)=1.010, 95 % Confidence interval (CI): 1.000～1.020, P=0.046; OR=1.017, 95 %CI:1.003-1.031, P=0.019), the association between PM2.5 and the development of asthma, COPD and stroke (OR=1.013, 95 %CI:1.003-1.024, P=0.011; OR=1.010, 95 %CI:1.000-1.019, P=0.035; OR=1.019, 95 %CI:1.004-1.033, P=0.012). No significant associations were found between the rest of the air pollution exposures and diseases. Leave-one-out sensitivity analysis showed stable results. CONCLUSIONS: The study clarifies the relationship between air pollution and cardiovascular, respiratory, and nervous system diseases, providing valuable evidence for environmental pollution prevention and population health monitoring, and provides a clear direction and evidence for the subsequent investigation of the association between air pollution and diseases.

Ambient PM2.5 components and prevalence of chronic kidney disease: a nationwide cross-sectional survey in China.

OBJECTIVES: Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. METHODS: Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. RESULTS: There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 µg/m3), SO42- (9.7 µg/m3), and OM (16.2 µg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. CONCLUSIONS: Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.

Lower regional urbanicity and socioeconomic status attenuate associations of green spaces with hypertension and diabetes mellitus: a national representative cross-sectional study in China.

BACKGROUND: High blood pressure (HBP) and diabetes mellitus (DM) are two of the most prevalent cardiometabolic disorders globally, especially among individuals with lower socio-economic status (SES). Studies have linked residential greenness to decreased risks of HBP and DM. However, there has been limited evidence on whether SES may modify the associations of residential greenness with HBP and DM. METHODS: Based on a national representative cross-sectional study among 44,876 adults, we generated the normalized difference vegetation index (NDVI) at 1 km spatial resolution to characterize individuals' residential greenness level. Administrative classification (urban/rural), nighttime light index (NLI), individual income, and educational levels were used to characterize regional urbanicity and individual SES levels. RESULTS: We observed weaker inverse associations of NDVI with HBP and DM in rural regions compared to urban regions. For instance, along with per interquartile range (IQR, 0.26) increment in residential NDVI at 0∼5 year moving averages, the ORs of HBP were 1.04 (95%CI: 0.94, 1.15) in rural regions and 0.85 (95%CI: 0.79, 0.93) in urban regions (P = 0.003). Along with the decrease in NLI levels, there were continuously decreasing inverse associations of NDVI with DM prevalence (P for interaction <0.001). In addition, weaker inverse associations of residential NDVI with HBP and DM prevalence were found among individuals with lower income and lower education levels compared to their counterparts. CONCLUSIONS: Lower regional urbanicity and individual SES could attenuate the associations of residential greenness with odds of HBP and DM prevalence.

c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly aggressive with a poor clinical prognosis and no targeted therapy. The c-Myc protein is a master transcription factor and a potential therapeutic target for TNBC. In this study, we develop a PROTAC (PROteolysis TArgeting Chimera) based on TNA (threose nucleic acid) and DNA that effectively targets and degrades c-Myc. The TNA aptamer is selected in vitro to bind the c-Myc/Max heterodimer and appended to the E-box DNA sequence to create a high-affinity, biologically stable bivalent binder. The TNA-E box-pomalidomide (TEP) conjugate specifically degrades endogenous c-Myc/Max, inhibits TNBC cell proliferation, and sensitizes TNBC cells to the cyclin-dependent kinase inhibitor palbociclib in vitro. In a mouse TNBC model, combination therapy with TEP and palbociclib potently suppresses tumor growth. This study offers a promising nucleic acid-based PROTAC modality for both chemical biology studies and therapeutic interventions of TNBC.

Selection of RNA-Cleaving TNA Enzymes for Cellular Mg2+ Imaging.

Catalytic DNA-based fluorescent sensors have enabled cellular imaging of metal ions such as Mg2+ . However, natural DNA is prone to nuclease-mediated degradation. Here, we report the in vitro selection of threose nucleic acid enzymes (TNAzymes) with RNA endonuclease activities. One such TNAzyme, T17-22, catalyzes a site-specific RNA cleavage reaction with a kcat of 0.017 min-1 and KM of 675 nM. A fluorescent sensor based on T17-22 responds to an increasing concentration of Mg2+ with a limit of detection at 0.35 mM. This TNAzyme-based sensor also allows cellular imaging of Mg2+ . This work presents the first proof-of-concept demonstration of using a TNA catalyst in cellular metal ion imaging.

Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/ß-catenin signalling pathway.

CONTEXT: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood. OBJECTIVE: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis. MATERIALS AND METHODS: We used male ApoE-/- mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/ß-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively. RESULTS: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25 mm2 vs. 0.46 mm2), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm2 vs. 98.02/mm2). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), ß-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), ß-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57). DISCUSSION AND CONCLUSIONS: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.

Exploring complex water stress-gross primary production relationships: Impact of climatic drivers, main effects, and interactive effects.

The dominance of vapor pressure deficit (VPD) and soil water content (SWC) for plant water stress is still under debate. These two variables are strongly coupled and influenced by climatic drivers. The impacts of climatic drivers on the relationships between gross primary production (GPP) and water stress from VPD/SWC and the interaction between VPD and SWC are not fully understood. Here, applying statistical methods and extreme gradient boosting models-Shapley additive explanations framework to eddy-covariance observations from the global FLUXNET2015 data set, we found that the VPD-GPP relationship was strongly influenced by climatic interactions and that VPD was more important for plant water stress than SWC across most plant functional types when we removed the effect of main climatic drivers, e.g. air temperature, incoming shortwave radiation and wind speed. However, we found no evidence for a significant influence of elevated CO2 on stress alleviation, possibly because of the short duration of the records (approximately one decade). Additionally, the interactive effect between VPD and SWC differed from their individual effect. When SWC was high, the SHAP interaction value of SWC and VPD on GPP was decreased with increasing VPD, but when SWC was low, the trend was the opposite. Additionally, we revealed a threshold effect for VPD stress on GPP loss; above the threshold value, the stress on GPP was flattened off. Our results have important implications for independently identifying VPD and SWC limitations on plant productivity, which is meaningful for capturing the magnitude of ecosystem responses to water stress in dynamic global vegetation models.

A review of plant antipathogenic constituents: Source, activity and mechanism.

Green prevention and control of plant pathogens is a development direction of sustainable and low-carbon agriculture given the limitation of traditional chemicals. Plant-derived antipathogenic constituents (PAPCs) exhibit the advantages of being environmental benign and a broad spectrum of target pathogens over traditional chemicals. Here, we review the research advances on plant sources, chemical compositions, activities of antipathogenic constituents in the past 20 years. Reported PAPCs are classified into categories of phenols, flavonoids, terpenoids, alkaloids and antimicrobial peptides. Angiosperms, gymnosperms and some lower plants are the main plant source of detected PAPCs. The PAPCs act on pathogens through multiple pathways including destroying cell structures, blocking key composition synthesis and inhibiting cell metabolism. The development trends of PAPCs are finally prospected. This review serves as a comprehensive review on the study of plant antipathogenic constituents and a key reference for forecasting the source, characteristic and activity of PAPC.

The NLRP3 inflammasome: Multiple activation pathways and its role in primary cells during ventricular remodeling.

Inflammasomes are a group of multiprotein signaling complexes located in the cytoplasm. Several inflammasomes have been identified, including NLRP1, NLRP2, NLRP3, AIM2, and NLRC4. Among them, NLRP3 was investigated in most detail, and it was reported that it can be activated by many different stimuli. Increased NLRP3 protein expression and inflammasome assembly lead to caspase-1 mediated maturation and release of IL-1ß, which triggers inflammation and pyroptosis. The activation of the NLRP3 inflammasome has been widely reported in studies of tumors and neurological diseases, but relatively few studies on the cardiovascular system. Ventricular remodeling (VR) is an important factor contributing to heart failure (HF) after myocardial infarction (MI). Consequently, delaying VR is of great significance for improving heart function. Studies have shown that the NLRP3 inflammasome plays an essential role in the process of VR. Here, we reviewed the latest studies on the activation pathway of the NLRP3 inflammasome, focusing on the effects of the NLRP3 inflammasome in primary cells during VR, and finally discuss future research directions in this field.

A Threose Nucleic Acid Enzyme with RNA Ligase Activity.

Threose nucleic acid (TNA) has been considered a potential RNA progenitor in evolution due to its chemical simplicity and base pairing property. Catalytic TNA sequences with RNA ligase activities might have facilitated the transition to the RNA world. Here we report the isolation of RNA ligase TNA enzymes by in vitro selection. The identified TNA enzyme T8-6 catalyzes the formation of a 2'-5' phosphoester bond between a 2',3'-diol and a 5'-triphosphate group, with a kobs of 1.1 × 10-2 min-1 (40 mM Mg2+, pH 9.0). For efficient reaction, T8-6 requires UA|GA at the ligation junction and tolerates variations at other substrate positions. Functional RNAs such as hammerhead ribozyme can be prepared by T8-6-catalyzed ligation, with site-specific introduction of a 2'-5' linkage. Together, this work provides experimental support for TNA as a plausible pre-RNA genetic polymer and also offers an alternative molecular tool for biotechnology.

Adolescents' Judgment of Homophobic Name-Calling: The Role of Peer/Friend Context and Emotional Response.

Adolescents use some types of homophobic language (e.g., "that's so gay") as a form of banter, while other types are directly targeted as an intentional insult (e.g., calling someone a "fag, dyke, homo"). Little research has investigated adolescents' use and judgments about these types of homophobic language and whether judgments differ if they are used among friends or directed toward non-friend peers. This study investigated how relationship context and victim's (N = 477, Mage = 14.7, SD = 1.63) emotional responses related to judgments about anti-gay banter and homophobic name-calling. Adolescents evaluated homophobic name-calling as more wrong than anti-gay banter. While adolescents' evaluations of homophobic name-calling did not differ based on relationship context, adolescents did differentiate between anti-gay banter perpetrated by a friend vs. a peer. Further, emotional responses mediated these relationships in the anti-gay banter situation. These results suggest that adolescents' judgments about homophobic language are related to the relationship context and the type of homophobic language used.

In Situ Synthesis of (Mo,Cr)Si2 Composites by Spark Plasma Sintering.

This research investigated the impact of Cr content on the properties of (Mo,Cr)Si2 composites. Composites with CrSi2 molar fractions ranging from 0% to 10% were fabricated using spark plasma sintering (SPS). The study undertook a systematic analysis of the surface morphology, phase composition, mechanical properties, and high-temperature oxidation resistance of the sintered samples across different compositions. Notably, the (Mo95,Cr5)Si2 composite sintered at 1400 °C exhibited enhanced properties, including a Vickers hardness of 11.6 GPa, a fracture toughness of 4.6 MPa·m1/2, and a flexural strength of 397 MPa. Upon oxidation at 1500 °C, the (Mo,Cr)Si2 composites formed a protective oxide layer comprised of SiO2 and Cr2O3. It was found that the generation and thickening of the protective oxide layer was promoted by the addition of moderate amounts of Cr to MoSi2.

Stigma and lesbian, gay, bisexual, transgender, and queer (and additional identities) (LGBTQ+) parent socialization self-efficacy: Mediating roles of identity and community.

In the United States, cultural forces have led to the stigmatization of lesbian, gay, bisexual, transgender, and queer (and additional identities) (LGBTQ+) parenthood. However, pushing back against this stigmatization, developing a positive LGBTQ+ identity, and investing in one's LGBTQ+ community may inform empowering narratives of future parenthood and related constructs, such as LGBTQ+ parent socialization. Perceived self-efficacy related to preparation for bias (i.e., discussions of discrimination, prejudice, or bias-based bullying) socialization is likely associated with an individual's own perceptions or experiences of stigmatization given the conceptual overlap of bias and stigma. However, other constructs related to stigmatization and socialization self-efficacy, such as positive LGBTQ+ identity or community connectedness, have yet to be simultaneously considered (to our knowledge). Further, previous research has rarely included different assessments of stigma (i.e., perceived and enacted) and/or dimensions of positive LGBTQ+ identity (i.e., authenticity and self-awareness). Thus, this study aimed to rectify these gaps and provide a greater understanding of sexual stigma and LGBTQ+ parent socialization self-efficacy. Using data from a survey-based, online, cross-sectional study of LGBTQ+ childfree adults (N = 433; Mage = 29.85 years old) in the United States, we found that experiences of enacted or perceived sexual stigma were differentially associated with LGBTQ+ parent socialization preparation for bias self-efficacy. Further, positive LGBTQ+ identity authenticity and self-awareness, as well as LGBTQ+ community connectedness played distinct roles as mediators of the relationships between sexual stigma and LGBTQ+ parent socialization self-efficacy. These findings have implications for how we might understand the role of stigma, identity, community, and socialization among future LGBTQ+ parents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Causality between allergic diseases and kidney diseases: a two-sample Mendelian randomization study.

Background: Evidence from observational studies and clinical trials suggests that the allergic diseases (ADs) are associated with kidney diseases (KDs). However, the causal association between them remains to be determined. We used bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the potential causality between them. Methods: Mendelian randomization (MR) was performed using publicly available genome-wide association study (GWAS) summary datasets. Inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods are used to evaluate the causality between ADs and KDs. Sensitivity and heterogeneity analyses were used to ensure the stability of the results. Results: The MR results indicated that genetic susceptibility to ADs was associated with a higher risk of CKD [odds ratio (OR) = 1.124, 95% CI = 1.020-1.239, p = 0.019] and unspecified kidney failure (OR = 1.170, 95% CI = 1.004-1.363, p = 0.045) but not with kidney stone, ureter stone or bladder stone (OR = 1.001, 95% CI = 1.000-1.002, p = 0.216), other renal or kidney problem (OR = 1.000, 95% CI = 1.000-1.001, p = 0.339), urinary tract or kidney infection (OR = 1.000, 95% CI = 0.999-1.001, p = 0.604), kidney volume (OR = 0.996, 95% CI = 0.960-1.033, p = 0.812) and cyst of kidney (OR = 0.914, 95% CI = 0.756-1.105, p = 0.354). No causal evidence of KDs on ADs was found in present study. Conclusion: Results from MR analysis indicate a causal association between ADs and CKD and unspecified kidney failure. These findings partly suggest that early monitoring of CKD risk in patients with ADs is intentional.

Bimetallic Ag/Au nanoclusters encapsulated in ZIF-8 framework: A novel strategy for ratiometric fluorescence detection of doxycycline in food.

This study successfully encapsulated the Ag+-doped Au nanoclusters (Ag/AuNCs) within the ZIF-8 framework to construct a novel Ag/AuNCs@ZIF-8 ratiometric fluorescent probe for the antibiotic doxycycline (DOX) detection. The incorporation of Ag+ contributed to the fluorescence enhancement of the nanoclusters through the "silver effect", consequently improving the stability of the developed bimetallic Ag/AuNCs. Furthermore, the encapsulation of bimetallic Ag/AuNCs within the ZIF-8 framework restricted their intramolecular vibrations, resulting in further amplification of fluorescence intensity at 595 nm. The ZIF-8 also sensitized the restoration of DOX green fluorescence at 515 nm. Within the concentration range of 0.001-20 µg mL-1, the ratio of fluorescence intensity (F515/F595) exhibited a favorable linearity for DOX concentration, with a detection limit of 36.8 ng mL-1. This ratiometric fluorescence approach had the promising potential for accurate and efficient quantitative detection of DOX residue in food and served as a valuable reference for rapid monitoring of food contaminants.

Aquatic life criteria of hydrothermal liquefaction wastewater via ecotoxicity test and modeling.

Wastewater resulting from hydrothermal liquefaction (HTL-AP) of biowaste is gaining attention as an emerging hazardous material. However, there is a lack of specific and systematic ecotoxicity studies on HTL-AP. This study addresses this gap by conducting acute toxicity tests on HTL-AP using typical aquatic species and integrating these results with predicted toxicity values from interspecies correlation estimation models to establish aquatic life criteria. HTL-AP exhibited significant toxicity with LC50 of 956.12-3645.4 mg/L, but demonstrated moderate toxicity compared to common freshwater pollutants like commercial microbicides, personal care products, and insect repellents. The resulting hazardous concentration for 5 % of species (HC5), the criterion maximum concentration, and the short-term water quality criteria for aquatic were 506.0, 253.0, and 168.7 mg/L, respectively. Notably, certain organisms like Misgurnus anguillicaudatus and Cipangopaludina chinensis showed high tolerance to HTL-AP, likely due to their metabolic capabilities on HTL-AP components. The significant decrease in HC5 values for some HTL-AP substances compared to pure compounds could indicate the synergistic inhibition effects among HTL-AP compositions. Furthermore, according to the established criteria, HTL-AP required significantly less diluted water (13 t) than carbendazim (1009 t) to achieve biosafety, indicating a safer release. This research establishes a preliminary water quality criterion for HTL-AP, offering a valuable reference for risk assessment and prediction in the utilization of HTL-AP within environmental contexts.

Microfluidic paper-based analysis device applying black phosphorus nanosheets@MWCNTs-COOH: A portable and efficient strategy for detection of ß-Lactoglobulin in dairy products.

This study prepared a novel, portable and cost-effective microfluidic paper-based electrochemical analysis device (µ-PAD) using black phosphorus nanosheets@carboxylated multi-walled carbon nanotubes (BPNSs@MWCNTs-COOH) nanocomposites for ß-lactoglobulin (ß-LG) detection. At the appreciate ratio, the synthesized BPNSs@MWCNTs-COOH was demonstrated to not only serve as a high-quality substrate for the specific aptamer immobilization, but also improve the electron transfer capability of the sensing interface. The µ-PADs, utilizing BPNSs@MWCNTs-COOH and aptamer recognition, exhibited a wider detection range (10-1000 ng mL-1) and lower detection limit (LOD: 0.12 ng mL-1) for ß-LG, and demonstrated enhanced specificity, satisfactory anti-interference ability and stability. When applied to the ß-LG determination in dairy samples, the µ-PAD yielded ß-LG concentrations highly correlated with those obtained using the HPLC method (R2: 0.9982). These results emphasized the reliable performance of the developed µ-PADs in ß-LG allergen quantification, highlighting their potential as an efficient platform for the rapid screening of ß-LG allergens.

European and African-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites.

Initially focused on the European population, multiple genome-wide association studies (GWAS) of complex diseases, such as type-2 diabetes (T2D), have now extended to other populations. However, to date, few ancestry-matched omics datasets have been generated or further integrated with the disease GWAS to nominate the key genes and/or molecular traits underlying the disease risk loci. In this study, we generated and integrated plasma proteomics and metabolomics with array-based genotype datasets of European (EUR) and African (AFR) ancestries to identify ancestry-specific muti-omics quantitative trait loci (QTLs). We further applied these QTLs to ancestry-stratified T2D risk to pinpoint key proteins and metabolites underlying the disease-associated genetic loci. We nominated five proteins and four metabolites in the European group and one protein and one metabolite in the African group to be part of the molecular pathways of T2D risk in an ancestry-stratified manner. Our study demonstrates the integration of genetic and omic studies of different ancestries can be used to identify distinct effector molecular traits underlying the same disease across diverse populations. Specifically, in the AFR proteomic findings on T2D, we prioritized the protein QSOX2; while in the AFR metabolomic findings, we pinpointed the metabolite GlcNAc sulfate conjugate of C21H34O2 steroid. Neither of these findings overlapped with the corresponding EUR results.

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

Review: Synthesis of metal organic framework-based composites for application as immunosensors in food safety.

Ensuring food safety continues to be one of the major global challenges. For effective food safety monitoring, fast, sensitive, portable, and efficient food safety detection strategies must be devised. Metal organic frameworks (MOFs) are porous crystalline materials that have attracted attention for use in high-performance sensors for food safety detection owing to their advantages such as high porosity, large specific surface area, adjustable structure, and easy surface functional modification. Immunoassay strategies based on antigen-antibody specific binding are one of the important means for accurate and rapid detection of trace contaminants in food. Emerging MOFs and their composites with excellent properties are being synthesized, providing new ideas for immunoassays. This article summarizes the synthesis strategies of MOFs and MOF-based composites and their applications in the immunoassays of food contaminants. The challenges and prospects of the preparation and immunoassay applications of MOF-based composites are also presented. The findings of this study will contribute to the development and application of novel MOF-based composites with excellent properties and provide insights into advanced and efficient strategies for developing immunoassays.