Assessing long-term effects of gaseous air pollution exposure on mortality in the United States using a variant of difference-in-differences analysis.

Long-term mortality effects of particulate air pollution have been investigated in a causal analytic frame, while causal evidence for associations with gaseous air pollutants remains extensively lacking, especially for carbon monoxide (CO) and sulfur dioxide (SO2). In this study, we estimated the causal relationship of long-term exposure to nitrogen dioxide (NO2), CO, SO2, and ozone (O3) with mortality. Utilizing the data from National Morbidity, Mortality, and Air Pollution Study, we applied a variant of difference-in-differences (DID) method with conditional Poisson regression and generalized weighted quantile sum regression (gWQS) to investigate the independent and joint effects. Independent exposures to NO2, CO, and SO2 were causally associated with increased risks of total, nonaccidental, and cardiovascular mortality, while no evident associations with O3 were identified in the entire population. In gWQS analyses, an interquartile range-equivalent increase in mixture exposure was associated with a relative risk of 1.067 (95% confidence interval: 1.010-1.126) for total mortality, 1.067 (1.009-1.128) for nonaccidental mortality, and 1.125 (1.060-1.193) for cardiovascular mortality, where NO2 was identified as the most significant contributor to the overall effect. This nationwide DID analysis provided causal evidence for independent and combined effects of NO2, CO, SO2, and O3 on increased mortality risks among the US general population.

Multi-omics analysis of the prognostic and biological role of cuproptosis-related gene in gastric cancer.

Background: A considerable number of gastric cancer (GC) patients cannot receive benefits from current treatments. We aimed to identify possible biomarkers of cuproptosis-related genes (CRGs) in GC patients, which may help guide precision medicine-based decision-making. Methods: RNA sequencing data, copy number variations (CNVs) data, and single nucleotide variant (SNV) data were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Cancer Analysis (GSCA) database. Chi-squared test was adopted to screen differentially expressed CRGs (DE-CRGs) between samples from 14 kinds of carcinoma and adjacent tissue samples. Then, GC samples were divided into high- and low-expressed groups based on DE-CRGs for further survival analyses and the selection of biomarkers. Methylation sites related with biomarkers were acquired. The correlation between immune cells and biomarkers was verified. Finally, miRNA-mRNA, TFs-mRNA, and co-expression networks were established to detect factors with regulating effects on biomarkers. Results: Three CRGs including LIAS, GLS, and CDKN2A were identified as biomarkers in GC patients. Three methylation sites with a significant survival effect including cg13601799, 07562918, and 07253264 were acquired. Then, we found that B cells native was significantly correlated with CDKN2A, four immune cells such as T cells regulatory are significantly correlated with GLS, and two immune cells such as T cells CD4 memory activated were significantly correlated with LIAS. Moreover, 10 miRNAs in the miRNA-mRNA network and three transcription factors (TFs) in the TFs-mRNA network had a significant correlation with overall survival (OS). Finally, 20 enrichment functions were obtained on the basis of the co-expression network. Conclusions: Three biomarkers with a prognosis prediction value of GC were found, and multi-factor regulatory networks were constructed to screen out 13 factors with regulating influences of biomarkers.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Synthesis and Herbicidal Activity of 2-(2-Oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic Acids.

The discovery of a lead compound is fundamental to herbicide innovation, but the limited availability of valuable lead compounds has hindered their development in recent years. By utilizing the structural diversity-oriented inactive group strategy, 3-(2-pyridyl)-benzothiazol-2-one was identified as a promising lead scaffold for herbicides, starting from benzothiazole which is an inactive moiety commonly found in herbicides such as mefenacet, benazolin, benzthiazuron, and fenthiaprop-ethyl. To investigate the structure-activity relationship (SAR) of these chemicals, a series of 2-(2-oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic acid derivatives (VI01 ∼ VI28) were synthesized through classical nucleophilic SNAr reaction using halogenated pyridines and 6-methoxybenzothiazole-2-one. The chemical structures of all the title compounds were confirmed by NMR and MS analysis. Petri dish assays indicated that many compounds exhibited potent herbicidal activity against both broad-leaf weeds and grass weeds at 1.0 mg/L. The SAR analysis revealed that the presence of a trifluoromethyl group at the 5-position of pyridine is essential for herbicidal activity. Furthermore, carboxylic esters exhibit higher herbicidal activity compared to carboxylic amides and free acids, and the activity decreased with the extension of the carbon chain. The postemergence herbicidal activity of VI03 against 16 species of weeds was tested by pot experiments in a greenhouse. VI03 demonstrated comparable efficacy in controlling broadleaf weeds and superior efficacy in controlling grass weeds compared to carfentrazone ethyl. The present study has unveiled a novel molecular scaffold exhibiting remarkably potent herbicidal activity. These findings are anticipated to provide valuable insights for the advancement of new herbicides and offer an alternative approach for managing resistant weeds.

Application of conventional ultrasound coupled with shear wave elastography in the assessment of muscle strength in patients with type 2 diabetes.

Background: In patients with type 2 diabetes mellitus (T2DM), a decrease in muscle function may be related to changes in the biomechanical properties of skeletal muscles. However, the correlations between muscle function and the characteristics of muscle size and stiffness as measured by ultrasound in patients with T2DM are unclear. The aim of this study was to investigate the abilities of conventional ultrasound and shear wave elastography (SWE) to assess muscle properties in patients with T2DM and to correlate the findings with isokinetic muscle testing and functional tests. Methods: Sixty patients from the Department of Endocrinology in The Third Affiliated Hospital of Southern Medical University diagnosed with T2DM were recruited in this cross-sectional study from September 2021 to September 2022. T2DM was defined based on the American Diabetes Association criteria. The exclusion criteria were a history of injury or operation of the lower limb or clinical signs of neuromuscular disorders, any muscle-induced disease, and the presence of other types of diabetes mellitus. Thirty-five matched healthy volunteers were continuously included in the control group. SWE was used to measure the muscle stiffness of the quadriceps femoris [vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM), vastus intermedius (VI)] and the biceps brachii (BB) in a relaxed position, and the shear wave velocity (SWV) values were recorded. Muscle size was measured using conventional ultrasound. The participants underwent isokinetic knee extension/flexion (60°/sec) to assess muscle strength and functional tests of physical performance, including the short physical performance battery, 30-s chair stand test, timed up-and-go test, and 6-meter walk test. All demographics and measured variables were compared using the independent samples t-test. Interclass correlation coefficient analysis was performed on the measurement data obtained by the two operators, and Pearson correlation coefficients were used to determine the relationships between variables. Results: Patients with T2DM exhibited worse physical performance (P<0.05) and weaker lower limb muscle strength (P<0.05) than did healthy controls, but their handgrip strength was comparable (P=0.102). Patients with T2DM had significantly decreased muscle thickness [RF thickness: 10.69±3.21 vs. 13.09±2.41 mm, mean difference =-2.40, 95% confidence interval (CI): -3.56 to -1.24, P<0.001; anterior quadriceps thickness: 23.45±7.11 vs. 27.25±5.25 mm, mean difference =-3.80, 95% CI: -6.33 to -1.26, P=0.004] and RF cross-sectional area (3.04±1.10 vs. 4.11±0.95 cm2, mean difference =-1.07, 95% CI: -1.49 to -0.64; P<0.001) compared to healthy controls. Smaller muscle size was associated with decreased muscle strength (r=0.44-0.69, all P values <0.001). Except for the BB (3.48±0.38 vs. 3.61±0.61 m/s, mean difference =-0.12, 95% CI: -0.35 to 0.11; P=0.257) and VI (2.59±0.34 vs. 2.52±0.23 m/s, mean difference =0.03, 95% CI: -0.06 to 0.18; P=0.299), the muscle stiffness in patients with T2DM was significantly decreased. For the patients with T2DM and healthy participants, the SWV of the RF was 1.66±0.23 and 1.83±0.18 m/s (mean difference =-0.17, 95% CI: -0.25 to -0.08; P<0.001), respectively; that of the VM was 1.34±0.15 and 1.51±0.16 m/s (mean difference =-0.17, 95% CI: -0.24 to -0.10; P<0.001), respectively; and that of VL was 1.38±0.19 and 1.53±0.19 m/s (mean difference =-0.15, 95% CI: -0.23 to -0.07; P<0.001), respectively. Excellent interobserver reliability of the SWV measurements on the muscle of T2DM patients was observed (all intraclass correlation coefficients >0.75; P<0.001). The SWV showed moderate correlations with muscle strength in the RF, VM, and VL (r=0.30-0.61; all P values <0.05). Conclusions: Ultrasound technology exhibits good reliability for repeated measurements of muscle size and stiffness. Reduced muscle stiffness as detected by SWE was demonstrated in patients with diabetes and was associated with decreased muscle strength and impaired functional activity.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD. Despite this association, the extent of Met's protective effects on NAFLD through the modulation of ferroptosis has yet to be thoroughly investigated. In the present study, the administration of erastin or Ras-selective lethal 3 (RSL3), both known ferroptosis inducers, resulted in elevated cell mortality and reduced cell viability in AML12 hepatocytes. Notably, Met treatment demonstrated the capacity to mitigate these effects. Furthermore, we observed increased ferroptosis levels in both AML12 hepatocytes treated with palmitate and oleate (PA/OA) and in the liver tissue of db/db mice. Met treatment demonstrated significant reductions in iron accumulation and lipid-related reactive oxygen species production, simultaneously elevating the glutathione/glutathione disulfide ratio in both PA/OA-treated AML12 hepatocytes and the liver tissue of db/db mice. Interestingly, the anti-ferroptosis effects of Met were significantly reversed with the administration of RSL3, both in vitro and in vivo. Mechanistically, Met treatment regulated the glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 axis to alleviate ferroptosis in NAFLD hepatocytes. Overall, our findings highlight the crucial role of ferroptosis in the development of T2DM-related NAFLD and underscore the potential of Met in modulating key factors associated with ferroptosis in the context of NAFLD.

Engineered keratin/bFGF hydrogel to promote diabetic wound healing in rats.

Keratin materials are promising in wound healing acceleration, however, it is a challenge for the keratin to efficiently therapy the impaired wound healing, such as diabetic foot ulcers. Here, we report a keratin/bFGF hydrogel for skin repair of chronic wounds in diabetic rats based on their characteristics of extracellular matrix and growth factor degradation in diabetic ulcer. Recombinant keratin 31 (K31), the most abundant keratin in human hair, exhibited the highly efficient performances in cell adhesion, proliferation and migration. More importantly, the introduction of bFGF into K31 hydrogel significantly enhances the properties of cell proliferation, wound closure acceleration, angiogenesis and skin appendages regeneration. Furthermore, the combination of K31 and bFGF can promote epithelial-mesenchymal transition by inhibiting the expression of E-cadherin and promoting the expression of vimentin and fibronectin. These findings demonstrate the engineered K31/bFGF hydrogel as a promising therapeutic agent for diabetic wound healing.

Synthesis and herbicidal activities of 2-((3-pyridinyl-2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)oxy)propionates.

BACKGROUND: The discovery of lead compounds is fundamental to herbicide innovation, yet the limited availability of valuable lead compounds has impeded their progress in recent years. The study presents a novel molecular scaffold that exhibits remarkably potent herbicidal activity. RESULTS: Through a scaffold-hopping strategy, a highly potent lead compound for herbicides, namely 3-(2-pyridinyl)-benzothiazol-2-one, was unexpectedly discovered during attempts to structurally modify haloxyfop, a commercial aryl-oxy-phenoxy-propionate herbicide. To investigate the structure-activity relationship (SAR) of the newly discovered herbicidal chemicals, a series of 2-(2-oxo-3-(pyridin-2-yl)-2,3-dihydrobenzo[d]thiazol-6-yloxy)propanoic acid derivatives, I-01 ~ I-27, were designed and synthesized. SAR analysis revealed that trifluoromethyl at the 5-position of pyridine is crucial for herbicidal activity, whereas additional fluorine or Cl atom at the 3-position of pyridine significantly enhances activity. Carboxylic ester derivatives exhibit superior herbicidal activity compared with amide derivatives. Moreover, the activity of carboxylic ester derivatives decreases with C chain extension, but the introduction of O atoms in the side chain benefits activity enhancement. Pot experiments conducted in a glasshouse demonstrated that I-01 and I-09 exhibited potent postemergence herbicidal activity against broadleaf weeds, and completely inhibited growth of Amaranthus retroflex, Abutilon theophrasti and Portulaca oleracea at a dosage of 75 g ha-1. CONCLUSION: Despite the initial goal of scaffold-hopping not being achieved, we have successfully identified a novel molecular scaffold exhibiting exceptional herbicidal activity, thereby presenting innovative prospects for herbicide development. © 2024 Society of Chemical Industry.

Outstanding issues in the study of antipredator defenses.

Protective defense mechanisms are well documented across the animal kingdom, but there are still examples of antipredator defenses that do not fit easily into the current conceptualization. They either fall within the intersection of multiple mechanisms or fail to fall neatly into pre-existing categories. Here, using Endler's predatory sequence as a framework, we identify problematic examples of antipredator defenses, separating them into protective mechanisms that are difficult to classify and those which act sequentially depending on context. We then discuss three ways of improving underlying terminological and definitional problems: (1) issues with English and polysemy, (2) overlapping aspects of similar mechanisms, and (3) unclear definitions. By scrutinizing the literature, we disentangle several opaque areas in the study of protective defense mechanisms and highlight questions that require further research. An unclear conceptual framework for protective defense mechanisms can lead to misconceptions in understanding the costs and benefits of defenses displayed by animals, while interchangeable terminologies and ambiguous definitions can hinder communication in antipredator studies.

Predict the Gelling Properties of Alkali-Induced Egg White Gel Based on the Freshness of Duck Eggs.

Preserved egg white (PEW) has excellent gelling properties but is susceptible to the freshness of raw eggs. In this study, the correlation between the comprehensive freshness index (CFI) of raw eggs and the gelling properties of alkali-induced egg white gel (EWG) was elucidated. Results showed that the CFI, established by a principal component analysis (PCA) and stepwise regression analysis (SRA) methods, can be used to predict the freshness of duck eggs under storage conditions of 25 °C and 4 °C. A correlation analysis demonstrated that the CFI showed a strong negative correlation with the hardness and chewiness of alkali-induced EWG and a strong positive correlation with resilience within 12 days of storage at 25 °C and 20 days at 4 °C (p < 0.01). It might be due to the decrease in α-helix and disulfide bonds, as well as the hydrophobic interactions showing a first decrease and then an increase within the tested days. This study can provide an important theoretical basis for preserved egg pickling.

Effects of microbial agent and microbial fertilizer input on soil microbial community structure and diversity in a peanut continuous cropping system.

INTRODUCTION: The soil harbors a diverse array of microorganisms, and these are essential components of terrestrial ecosystems. The presence of microorganisms in the soil, particularly in the rhizosphere, is closely linked to plant growth and soil fertility. OBJECTIVE: The primary objective of this study is to assess the potential advantages of integrating microbial inoculants with compound fertilizer in enhancing peanut yield. METHODS: We utilized Illumina MiSeq high-throughput sequencing technology to conduct our investigation. The experimental design consists of four treatment groups: compound fertilizers (CF), compound fertilizers supplemented with microbial agents (CF + MA), compound fertilizers supplemented with microbial fertilizers (CF + MF), and compound fertilizers supplemented with both microbial agents and microbial fertilizers (CF + MM). RESULTS: The experimental results demonstrated a significant increase in peanut yield upon application of CF + MA, CF + MF, and CF + MM treatments. During the blossom stage and pod-setting stage, the soil's catalase, urease, and acid phosphatase activities were significantly increased in the CF + MA, and CF + MM treatments compared to the CF treatment. The application of CF + MA resulted in an increase in bacterial richness in the rhizosphere soil of peanuts, as indicated by the sequencing results. The application of CF + MA, CF + MF, and CF + MM resulted in a reduction of fungal diversity. Proteobacteria, Actinobacteria, and Acidobacteria were the dominant bacterial phyla, while Ascomycota and Basidiomycota were the dominant phyla in the fungal component of the rhizosphere soil microbiome across all experimental treatments. CONCLUSION: Microbial agents and fertilizers modify the peanut rhizosphere soil's microbial community structure, as per our findings. The abundance of potentially beneficial bacteria (Bradyrhizobium, Rhizobium, and Burkholderia) and fungi (Trichoderma and Cladophialophora) could increase, while pathogenic fungi (Penicillium and Fusarium) decreased, thereby significantly promoting plant growth and yield of peanut.

Collective motion in hcp-Fe at Earth's inner core conditions.

Earth's inner core is predominantly composed of solid iron (Fe) and displays intriguing properties such as strong shear softening and an ultrahigh Poisson's ratio. Insofar, physical mechanisms to explain these features coherently remain highly debated. Here, we have studied longitudinal and shear wave velocities of hcp-Fe (hexagonal close-packed iron) at relevant pressure-temperature conditions of the inner core using in situ shock experiments and machine learning molecular dynamics (MLMD) simulations. Our results demonstrate that the shear wave velocity of hcp-Fe along the Hugoniot in the premelting condition, defined as T/Tm (Tm: melting temperature of iron) above 0.96, is significantly reduced by ~30%, while Poisson's ratio jumps to approximately 0.44. MLMD simulations at 230 to 330 GPa indicate that collective motion with fast diffusive atomic migration occurs in premelting hcp-Fe primarily along [100] or [010] crystallographic direction, contributing to its elastic softening and enhanced Poisson's ratio. Our study reveals that hcp-Fe atoms can diffusively migrate to neighboring positions, forming open-loop and close-loop clusters in the inner core conditions. Hcp-Fe with collective motion at the inner core conditions is thus not an ideal solid previously believed. The premelting hcp-Fe with collective motion behaves like an extremely soft solid with an ultralow shear modulus and an ultrahigh Poisson's ratio that are consistent with seismic observations of the region. Our findings indicate that premelting hcp-Fe with fast diffusive motion represents the underlying physical mechanism to help explain the unique seismic and geodynamic features of the inner core.

Whole genome analysis of Bacillus amyloliquefaciens TA-1, a promising biocontrol agent against Cercospora arachidicola pathogen of early leaf spot in Arachis hypogaea L.

BACKGROUND: Early leaf spot disease, caused by Cercospora arachidicola, is a devastating peanut disease that has severely impacted peanut production and quality. Chemical fungicides pollute the environment; however, Bacillus bacteria can be used as an environmentally friendly alternative to chemical fungicides. To understand the novel bacterial strain and unravel its molecular mechanism, De novo whole-genome sequencing emerges as a rapid and efficient omics approach. RESULTS: In the current study, we identified an antagonistic strain, Bacillus amyloliquefaciens TA-1. In-vitro assay showed that the TA-1 strain was a strong antagonist against C. arachidicola, with an inhibition zone of 88.9 mm. In a greenhouse assay, results showed that the TA-1 strain had a significant biocontrol effect of 95% on peanut early leaf spot disease. De novo whole-genome sequencing analysis, shows that strain TA-1 has a single circular chromosome with 4172 protein-coding genes and a 45.91% guanine and cytosine (GC) content. Gene function was annotated using non-redundant proteins from the National Center for Biotechnology Information (NCBI), Swiss-Prot, the Kyoto Encyclopedia of Genes and Genomes (KEGG), clusters of orthologous groups of proteins, gene ontology, pathogen-host interactions, and carbohydrate-active enZYmes. antiSMASH analysis predicted that strain TA-1 can produce the secondary metabolites siderophore, tailcyclized peptide, myxochelin, bacillibactin, paenibactin, myxochelin, griseobactin, benarthin, tailcyclized, and samylocyclicin. CONCLUSION: The strain TA-1 had a significant biological control effect against peanut early leaf spot disease in-vitro and in greenhouse assays. Whole genome analysis revealed that, TA-1 strain belongs to B. amyloliquefaciens and could produce the antifungal secondary metabolites.

Residential greenness mitigates mortality risk from short-term airborne particulate exposure: An individual-level case-crossover study.

BACKGROUND: Studies suggested that greenness could reduce death risks related to ambient exposure to particulate matter (PM), while the available evidence was mixed across the globe and substantially exiguous in low- and middle-income countries. By conceiving an individual-level case-crossover study in central China, this analysis primarily aimed to quantify PM-mortality associations and examined the modification effect of greenness on the relationship. METHODS: We investigated a total of 177,058 nonaccidental death cases from 12 counties in central China, 2008-2012. Daily residential exposures to PM2.5 (aerodynamic diameter <2.5 µm), PMc (aerodynamic diameter between 2.5 and 10 µm), and PM10 (aerodynamic diameter <10 µm) were assessed at a 1 × 1-km resolution through satellite-derived machine-learning models. Residential surrounding greenness was assessed using satellite-derived enhanced vegetation index (EVI) and normalized difference vegetation index (NDVI) at multiple buffer sizes (250, 500, and 1000 m). To quantify the acute mortality risks associated with short-term exposure to PM2.5, PMc, and PM10, a time-stratified case-crossover design was utilized in conjunction with a conditional logistic regression model in our main analyses. To investigate the effect modification of greenness on PM-mortality associations, we grouped death cases into low, medium, and high greenness levels using cutoffs of 25th and 75th percentiles of NDVI or EVI exposure, and examined potential effect heterogeneity in PM-related mortality risks among these groups. RESULTS: Mean concentrations (standard deviation) on the day of death were 73.8 (33.4) µg/m3 for PM2.5, 43.9 (17.3) µg/m3 for PMc, and 117.5 (44.9) µg/m3 for PM10. Size-fractional PM exposures were consistently exhibited significant associations with elevated risks of nonaccidental and circulatory mortality. For every increase of 10-µg/m3 in PM exposure, percent excess risks of nonaccidental and circulatory mortality were 0.271 (95% confidence interval [CI]: 0.010, 0.533) and 0.487 (95% CI: 0.125, 0.851) for PM2.5 at lag-01 day, 0.731 (95% CI: 0.108, 1.359) and 1.140 (95% CI: 0.267, 2.019) for PMc at lag-02 day, and 0.271 (95% CI: 0.010, 0.533) and 0.386 (95% CI: 0.111, 0.662) for PM10 at lag-01 day, respectively. Compared to participants in the low-level greenness areas, those being exposed to higher greenness were found to be at lower PM-associated risks of nonaccidental and circulatory mortality. Consistent evidence for alleviated risks in medium or high greenness group was observed in subpopulations of female and younger groups (age <75). CONCLUSIONS: Short-term exposure to particulate air pollution was associated with elevated risks of nonaccidental and circulatory death, and individuals residing in higher neighborhood greenness possessed lower risk of PM-related mortality. These findings emphasized the potential public health advantages through incorporating green spaces into urban design and planning.

Tomato Aphid (Aphis gossypii) Secreted Saliva Can Enhance Aphid Resistance by Upregulating Signaling Molecules in Tomato (Solanum lycopersicum).

This study investigated the impact of Aphis gossypii watery saliva on the induction of tomato (Solanum lycopersicum) plant resistance. To examine the role of A. gossypii saliva, we collected watery saliva from A. gossypii after a 48 h feeding period on an artificial diet. SDS-PAGE resolving gel 12% was used to separate the salivary proteins. Relative expression of gene analysis revealed that the intrusion of A. gossypii saliva dripping onto S. lycopersicum leaves triggered robust defense responses mediated by a signaling molecule, i.e., salicylic acid, while the signaling molecule's jasmonic acid-dependent defense responses were moderately activated. Aphid saliva infiltrated S. lycopersicum leaves slowed the intrinsic rate of population growth of A. gossypii and significantly reduced the number of nymphs produced daily, compared to untreated leaves. During a choice test with untreated S. lycopersicum, aphids showed a repellent response towards saliva-infiltrated S. lycopersicum. Moreover, the (EPG) electrical penetration graph analysis demonstrated that the eating pattern of A. gossypii compared to untreated S. lycopersicum, that had been exposed to saliva was negatively impacted. These results provide compelling evidence for the involvement of salivary components of A. gossypii in inducing resistance against aphids in S. lycopersicum plants. Furthermore, the study underscores the crucial role of watery saliva in the intricate interactions between aphids and plants. The activation of pathways was also part of the defensive response (jasmonic acid (JA), salicylic acid (SA) signaling molecules). The findings of this research deliver valuable insights into the potential of watery aphid saliva as a natural defense mechanism against aphid infestations in S. lycopersicum crops.

N-benzyl-2-methoxy-5-propargyloxybenzoamides, a new type of bleaching herbicides targeting the biosynthesis pathway of plastoquinone.

BACKGROUND: Previously, the herbicidal activity of N-benzyl-2-methoxybenzamides was discovered during a random screening program in our laboratory. The chemicals resulted in bleaching effect of newly grown leaves by interfering with the biosynthesis of ß-carotene in plant. RESULTS: A total of 28 benzamides were synthesized and subjected for the evaluation of herbicidal activity. Structure-activity relationship (SAR) showed that introducing propargyloxy group at 5-position of benzoyl-benzene ring and fluorine or methyl group at 3- or 4-position of benzyl-benzene ring is beneficial for the activity. Post-emergence herbicidal activities of compounds 406 and 412 were comparable to those of mesotrione and diflufenican. Studies on MOA showed that 406 decreased the level of both ß-carotene and plastoquinone (PQ) in treated plants. The bleaching effect in green alga caused by 406 could be reversed by supplying exogenous homogentisic acid (HGA), the precursor of plastoquinone. CONCLUSION: N-benzyl-2-methoxy-5-propargyloxybenzoamides were discovered as new candidates for bleaching herbicides. Preliminary investigation on mechanism of action (MOA) showed that the title compounds might indirectly interfere with carotenoid biosynthesis by blocking the production of PQ. © 2023 Society of Chemical Industry.

Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN. METHODS: DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein-protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes. RESULTS: A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes. CONCLUSION: We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.

Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment.

By the year 2035 more than 4 billion people might be affected by obesity and being overweight. Adipocyte-derived Extracellular Vesicles (ADEVs/ADEV-singular) are essential for communication between the tumor microenvironment (TME) and obesity, emerging as a prominent mechanism of tumor progression. Adipose tissue (AT) becomes hypertrophic and hyperplastic in an obese state resulting in insulin resistance in the body. This modifies the energy supply to tumor cells and simultaneously stimulates the production of pro-inflammatory adipokines. In addition, obese AT has a dysregulated cargo content of discharged ADEVs, leading to elevated amounts of pro-inflammatory proteins, fatty acids, and carcinogenic microRNAs. ADEVs are strongly associated with hallmarks of cancer (proliferation and resistance to cell death, angiogenesis, invasion, metastasis, immunological response) and may be useful as biomarkers and antitumor therapy strategy. Given the present developments in obesity and cancer-related research, we conclude by outlining significant challenges and significant advances that must be addressed expeditiously to promote ADEVs research and clinical applications.

Label-free plasmonic metasensing of PSA and exosomes in serum for rapid high-sensitivity diagnosis of early prostate cancer.

Prostate-specific antigen (PSA) test is widely used to diagnose early prostate cancer (PCa). Its low sensitivity, especially in the gray zone, usually incurs overtreatment or missed diagnosis. As an emerging tumor marker, exosomes have attracted great interest in non-invasive diagnosis of PCa. However, the quick direct detection of exosomes in serum is still a big challenge for convenient screening of early PCa due to their high-degree heterogeneity and complexity. Here we develop the label-free biosensors based on wafer-scale plasmonic metasurfaces, and establish a flexible spectral methodology of exosomes profiling, which facilitates their identification and quantification in serum. We combine the metasurfaces functionalized by anti-PSA and anti-CD63, respectively, and build a portable immunoassay system to detect serum PSA and exosomes simultaneously within 20 min. Our scheme can discriminate early PCa from benign prostatic hyperplasia with a diagnostic sensitivity of 92.3%, which is much higher that of 58.3% for conventional PSA tests. The receiver operating characteristic analysis in clinical trials demonstrates significant PCa distinguishing capability with an area under the curve up to 99.4%. Our work provides a rapid and powerful approach for precise diagnosis of early PCa, and will inspire more exosomes metasensing studies for other early cancer screening.