Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11ß-HSD1.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear. AIM OF STUDY: This study aimed to identify the bioactive components of HXZQ responsible for its therapeutic effects on UC and to elucidate their underlying mechanisms. MATERIALS AND METHODS: The effect of HXZQ against dextran sodium sulfate (DSS) -induced colitis was investigated. Ingredients in HXZQ were characterized and analyzed in colitic mice using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). In vitro, biological activity of compounds was assessed using lipopolysaccharide (LPS)-induced Ana-1 cells and bone marrow-derived macrophages (BMDMs), tumor necrosis factor-alpha-induced Caco-2 cells, and isolated intestinal crypts from colitic mice. These results were confirmed in vivo. The targets of the components were identified through bioinformatics analysis and validated via molecular docking, enzyme inhibition assays, and in vivo experiments. Hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time polymerase chain reaction (qPCR) were employed to confirm the pharmaceutical effects. RESULTS: A clinical equivalent dose of HXZQ (2.5 mL/kg) effectively treated DSS-induced colitis. 113 compounds were identified in HXZQ, with 35 compounds detected in colitic mice. Glycyrrhizic acid (GA) and patchouli alcohol (PA) emerged as key contributors to the anti-colitic effects of HXZQ. Further investigation revealed that HXZQ and its active components decreased the levels of pro-inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in colon, likely by inhibiting nuclear factor kappa-B (NF-κB) signaling pathway. This inhibition indirectly activated the intestinal farnesoid X receptor (FXR) signaling pathway, correcting bile acid imbalances caused by colitis. Additionally, these components significantly enhanced the expression of tight junction proteins ZO-1 and Occludin, as well as the adhesion protein E-cadherin, and reduced goblet cell loss, thereby repairing intestinal barrier injury. Mechanistically, GA and PA were found to inhibit 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) activity, leading to increased local active corticosterone levels in the intestine to exert anti-inflammatory effects. Notably, the inhibition of 11ß-HSD1 with the selective inhibitor BVT ameliorated colitis in mice. CONCLUSIONS: HXZQ exhibits therapeutic effects on UC, primarily through GA and PA inhibiting 11ß-HSD1. This suggests new natural therapy approaches for UC and positions 11ß-HSD1 as a potential target for colitis treatment.

Prognostic implications of CK19 positivity in patients with early recurrent hepatocellular carcinoma after hepatic resection undergoing transarterial chemoembolization.

BACKGROUND: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression. METHODS: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS. RESULTS: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed. CONCLUSION: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals.

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Aryl Ketones Involving Free Phenolic Hydroxyl Group(s).

A straightforward asymmetric transfer hydrogenation for accessing enantiomerically enriched secondary benzyl alcohols involving free phenolic hydroxyl group(s) under mild conditions was developed. Various of optical pure aryl alcohols with a remarkable functional group compatibility were achieved with 78 %-97 % yields, 84 %->99 % ee's and up to 10 000 TON. This rhodium-catalyzed reaction could be performed in a gram-scale without loss of the efficiency. Furthermore, the synthetic utility has also been demonstrated in the asymmetric synthesis of (S)-adrenaline and (S)-phenylephrine.

Transjugular intrahepatic portosystemic shunt combined with dual-access thrombolysis for acute severe non-cirrhotic portal-mesenteric vein thrombosis.

OBJECTIVE: Non-cirrhotic porto-mesenteric vein thrombosis (NC-PMVT) is a rare but severe clinical condition. The study aims to assess the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) coupled with dual-access thrombolysis in patients with acute severe NC-PMVT. METHODS: From January 2018 to February 2023, a total of 25 patients with acute severe NC-PMVT who were treated with TIPS in conjunction with mechanical thrombectomy and dual-access thrombolysis. The period of thrombolysis was determined by the improvement of clinical symptoms and vascular recanalization. The technical success, recanalization rate, clinical success, and procedure-related complications were analyzed. RESULTS: The technical success rate was 100 %. The median duration for thrombolytic catheter removal was 5 (IQR 3.5 - 7) days. Full and partial recanalization were accomplished in 10 (40 %) and 15 (60 %) patients respectively before discharge. No significant procedure-related complications were reported. The clinical success rate was 88 %, with a mortality rate of 12 %. Over a median follow-up of 8 months, 3/22 (13.64 %) patients had a recurrence of thrombosis; 1/22 (4.54 %) patients underwent partial intestinal resection one and a half months post-discharge; the remaining patients did not experience any portal hypertensive complications. CONCLUSION: The combination of TIPS and dual-access thrombolysis appears to be safe and effective for patients with acute severe NC-PMVT.

DRA-UNet for Coal Mining Ground Surface Crack Delineation with UAV High-Resolution Images.

Coal mining in the Loess Plateau can very easily generate ground cracks, and these cracks can immediately result in ventilation trouble under the mine shaft, runoff disturbance, and vegetation destruction. Advanced UAV (Unmanned Aerial Vehicle) high-resolution mapping and DL (Deep Learning) are introduced as the key methods to quickly delineate coal mining ground surface cracks for disaster prevention. Firstly, the dataset named the Ground Cracks of Coal Mining Area Unmanned Aerial Vehicle (GCCMA-UAV) is built, with a ground resolution of 3 cm, which is suitable to make a 1:500 thematic map of the ground crack. This GCCMA-UAV dataset includes 6280 images of ground cracks, and the size of the imagery is 256 × 256 pixels. Secondly, the DRA-UNet model is built effectively for coal mining ground surface crack delineation. This DRA-UNet model is an improved UNet DL model, which mainly includes the DAM (Dual Dttention Dechanism) module, the RN (residual network) module, and the ASPP (Atrous Spatial Pyramid Pooling) module. The DRA-UNet model shows the highest recall rate of 77.29% when the DRA-UNet was compared with other similar DL models, such as DeepLabV3+, SegNet, PSPNet, and so on. DRA-UNet also has other relatively reliable indicators; the precision rate is 84.92% and the F1 score is 78.87%. Finally, DRA-UNet is applied to delineate cracks on a DOM (Digital Orthophoto Map) of 3 km2 in the mining workface area, with a ground resolution of 3 cm. There were 4903 cracks that were delineated from the DOM in the Huojitu Coal Mine Shaft. This DRA-UNet model effectively improves the efficiency of crack delineation.

Molecular basis of camphor repellency in Hyphantria cunea.

The plant-derived camphor has been used as a natural insect repellent against various insects for >500 years. However, the repellency mechanism behind camphor remains less understood. In this study, we aimed to identify the camphor receptor in Hyphantria cunea by deorphanizing 7 odorant receptors (ORs). The results showed that HcunOR46 is narrowly tuned to Camphor and is only conserved within the family Noctuidae. Further analysis through behavioral and electroantennograms (EAG) assays indicated that H. cunea adults are more sensitive to camphor than larvae, both behaviorally and electrophysiologically. This difference may be due to the lower expression of HcunOR46 at the larval stage. Additionally, a feeding assay indicated that camphor repellency could be related to camphor toxicity to larvae, with the lethal concentration 50 (LC50) value of 69.713 µg/µL. These results suggest that H. cunea may detect camphor through a distinct olfactory pathway from Culicinae mosquitos, providing a novel camphor-based pest management strategy for H. cunea.

Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-ß bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Residual and bidirectional LSTM for epileptic seizure detection.

Electroencephalogram (EEG) plays a pivotal role in the detection and analysis of epileptic seizures, which affects over 70 million people in the world. Nonetheless, the visual interpretation of EEG signals for epilepsy detection is laborious and time-consuming. To tackle this open challenge, we introduce a straightforward yet efficient hybrid deep learning approach, named ResBiLSTM, for detecting epileptic seizures using EEG signals. Firstly, a one-dimensional residual neural network (ResNet) is tailored to adeptly extract the local spatial features of EEG signals. Subsequently, the acquired features are input into a bidirectional long short-term memory (BiLSTM) layer to model temporal dependencies. These output features are further processed through two fully connected layers to achieve the final epileptic seizure detection. The performance of ResBiLSTM is assessed on the epileptic seizure datasets provided by the University of Bonn and Temple University Hospital (TUH). The ResBiLSTM model achieves epileptic seizure detection accuracy rates of 98.88-100% in binary and ternary classifications on the Bonn dataset. Experimental outcomes for seizure recognition across seven epilepsy seizure types on the TUH seizure corpus (TUSZ) dataset indicate that the ResBiLSTM model attains a classification accuracy of 95.03% and a weighted F1 score of 95.03% with 10-fold cross-validation. These findings illustrate that ResBiLSTM outperforms several recent deep learning state-of-the-art approaches.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

AST/ALT ratio is an independent risk factor for diabetic retinopathy: A cross-sectional study.

The aspartate to alanine transaminase (AST/ALT) ratio indicates oxidative stress and inflammatory reactions related to the occurrence of diabetic retinopathy (DR). Currently, there are no reports on the correlation between AST/ALT ratio and DR. Hence, this study aimed to explore the relationship between AST/ALT ratio and DR. This cross-sectional study utilized data from the Metabolic Management Center of the First People's Hospital in City. In total, 1365 patients with type 2 diabetes mellitus (T2DM) participated in the study, including 244 patients with DR and 1121 patients without DR. We collected the results of fundus photography, liver function, and other research data and grouped them according to tertiles of AST/ALT ratios. DR prevalence was the highest in the group with the highest AST/ALT ratio (22.12%, P = .004). Both univariate (OR = 2.25, 95% CI: 1.51-3.34, P < .001) and multivariable logistic regression analyses (adjusted for confounding factors) showed that the risk of DR increased by 36% when the AST/ALT ratio increased by 1 standard deviation (SD) (OR = 1.36, 95% CI: 1.16-1.59, P < .001), and 29.3% was mediated by the duration of diabetes. A sensitivity analysis confirmed the stability of the results. This study showed that an increase in AST/ALT ratio is an independent risk factor for DR.

Visceral fat area is more strongly associated with arterial stiffness than abdominal subcutaneous fat area in Chinese patients with type 2 diabetes.

BACKGROUND: Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. METHODS: In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. RESULTS: The baPWV was linked with VFA, waist circumference, and women's SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men's SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05). CONCLUSIONS: Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

Extracellular vesicles as modifiers of epigenomic profiles.

Extracellular vesicles (EVs), emerging as novel mediators between intercellular communication, encapsulate distinct bioactive cargoes to modulate multiple biological events, such as epigenetic remodeling. In essence, EVs and epigenomic profiles are tightly linked and reciprocally regulated. Epigenetic factors, including histone and DNA modifications, noncoding RNAs, and protein post-translational modifications (PTMs) dynamically regulate EV biogenesis to contribute to EV heterogeneity. Alternatively, EVs actively modify DNA, RNA, and histone profiles in recipient cells by delivering RNA and protein cargoes for downstream epigenetic enzyme regulation. Moreover, EVs display great potential as diagnostic markers and drug-delivery vehicles for therapeutic applications. The combination of parental cell epigenomic modification with single EV characterization would be a promising strategy for EV engineering to enhance the epidrug loading efficacy and accuracy.

Linearly Polarized Broadband Emission and Multiwavelength Lasing in Solution-Processed Quantum Dots.

A miniature laser with linear polarization is a long sought-after component of photonic integrated circuits. In particular, for multiwavelength polarization lasers, it supports simultaneous access to multiple, widely varying laser wavelengths in a small spatial region, which is of great significance for advancing applications such as optical computing, optical storage, and optical sensing. However, there is a trade-off between the size of small-scale lasers and laser performance, and multiwavelength co-gain of laser media and multicavity micromachining in the process of laser miniaturization remain as significant challenges. Herein, room-temperature linearly polarized multiwavelength lasers in the visible and near-infrared wavelength ranges are demonstrated, by fabricating random cavities scattered with silica in an Er-doped Cs2Ag0.4Na0.6In0.98Bi0.02Cl6 double-perovskite quantum dots gain membrane. By regulating the local symmetry and enabling effective energy transfer in nanocrystals, multiwavelength lasers with ultralow thresholds are achieved at room temperature. The maximum degree of polarization reaches 0.89. With their advantages in terms of miniaturization, ultralow power consumption, and adaptability for integration, these lasers offer a prospective light source for future photonic integrated circuits aimed at high-capacity optical applications.

Evaluation of Antioxidant Activity and Treatment of Eczema by Berberine Hydrochloride-Loaded Liposomes-in-Gel.

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 µg/cm2. BBH-L-Gel had a good scavenging capacity on DPPH and H2O2, and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4-2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment.

Selective adsorption of Cr(VI) by nitrogen-doped hydrothermal carbon in binary system.

Selective adsorption of heavy metal ions from industrial effluent is important for healthy ecosystem development. However, the selective adsorption of heavy metal pollutants by biochar using lignin as raw material is still a challenge. In this paper, the lignin carbon material (N-BLC) was synthesized by a one-step hydrothermal carbonization method using paper black liquor (BL) as raw material and triethylene diamine (TEDA) as nitrogen source. N-BLC (2:1) showed excellent selectivity for Cr(VI) in the binary system, and the adsorption amounts of Cr(VI) in the binary system were all greater than 150 mg/g, but the adsorption amounts of Ca(II), Mg(II), and Zn(II) were only 19.3, 25.5, and 6.3 mg/g, respectively. The separation factor (SF) for Cr(VI) adsorption was as high as 120.0. Meanwhile, FTIR, elemental analysis and XPS proved that the surface of N-BLC (2:1) contained many N- and O- containing groups which were favorable for the removal of Cr(VI). The adsorption of N-BLC (2:1) followed the Langmuir model and its maximum theoretical adsorption amount was 618.4 mg/g. After 5th recycling, the adsorption amount of Cr(VI) by N-BLC (2:1) decreased about 15%, showing a good regeneration ability. Therefore, N-BLC (2:1) is a highly efficient, selective and reusable Cr(VI) adsorbent with wide application prospects.

Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

An Environment-Tolerant Ion-Conducting Double-Network Composite Hydrogel for High-Performance Flexible Electronic Devices.

High-performance ion-conducting hydrogels (ICHs) are vital for developing flexible electronic devices. However, the robustness and ion-conducting behavior of ICHs deteriorate at extreme temperatures, hampering their use in soft electronics. To resolve these issues, a method involving freeze-thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network (DN) ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol) (PMP DN ICH) system. The well-designed ICH exhibits outstanding ionic conductivity (63.89 mS cm-1 at 25 °C), excellent temperature resistance (- 60-80 °C), prolonged stability (30 d at ambient temperature), high oxidation resistance, remarkable antibacterial activity, decent mechanical performance, and adhesion. Additionally, the ICH performs effectively in a flexible wireless strain sensor, thermal sensor, all-solid-state supercapacitor, and single-electrode triboelectric nanogenerator, thereby highlighting its viability in constructing soft electronic devices. The highly integrated gel structure endows these flexible electronic devices with stable, reliable signal output performance. In particular, the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm-2 (current density, 1 mA cm-2) and excellent environmental adaptability. This study paves the way for the design and fabrication of high-performance multifunctional/flexible ICHs for wearable sensing, energy-storage, and energy-harvesting applications.

1,2,4-Triazole benzamide derivative TPB against Gaeumannomyces graminis var. tritici as a novel dual-target fungicide inhibiting ergosterol synthesis and adenine nucleotide transferase function.

BACKGROUND: Isopropyl 4-(2-chloro-6-(1H-1,2,4-triazol-1-yl)benzamido)benzoate (TPB) was a 1,2,4-triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA-seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA-seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti-oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual-target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take-all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry.

Dietary shifts drive the slowdown of declining methylmercury related health risk in China.

Chinese population suffers severe health risk from dietary methylmercury (MeHg) exposure. However, the temporal change of such risk and socioeconomic driving factors remain unknown. This study investigates this issue by compiling time-series inventory of China's MeHg-related health risk at the provincial scale and revealing critical socioeconomic influencing factors through structural decomposition analysis. Results show that the per-fetus IQ decrements from dietary MeHg exposure have declined by 60% nationally during 2004-2019. Such decline results from the joint effects of dietary shifts (contributing 44%) and the decrease of MeHg concentrations in foods consumed (contributing 56%). However, the declining trend has slowed down since 2014 and even leveled off after 2016, which is mainly affected by dietary pattern changes. Especially, the increased intake level and proportion of fishes in underdeveloped provinces of China have dominated the slowdown of declining trend after 2016. Moreover, the affluence and education levels have significantly negative associations with per-fetus IQ decrements. Rich and well-educated people have higher ability of risk perception, which indicates the importance of rational consumption patterns. Our findings can help develop socioeconomic regulatory policies on reducing per-fetus IQ decrements from dietary MeHg exposure in China.

Positive correlation between lipid accumulation product index and arterial stiffness in Chinese patients with type 2 diabetes.

Background: Many studies have confirmed that lipid accumulation products (LAP) predict arterial stiffness (AS) in hypertensive patients. But there is little research on the use of LAP in identifying early atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to determine the relationship between the LAP index and brachial-ankle pulse wave velocity (baPWV) in Chinese patients with T2DM. Methods: A total of 1471 Chinese participants with T2DM, ranging in age from 18 to 80, were included in this cross-sectional study. BaPWV measurements were used to calculate the AS. A baPWV greater than the 75th percentile (1700 cm/s) was defined as indicating increased AS. The LAP index was calculated from the combination of waist circumference (WC) and triglycerides (TG). Results: According to the quartiles of the LAP index, baPWV tended to increase after adjusting for sex and age. Multiple linear regression analysis showed that the beta coefficient (ß) of baPWV increased by 31.0 cm/s for each unit of lnLAP that was increased, and the 95% confidence interval (CI) was (6.5, 55.5) cm/s. In multivariate logistic regression analyses, after fully adjusting for confounders, the risk of elevated baPWV increased with each unit increase in lnLAP, with an odds ratio (OR) of 1.3 (95% CI: 1.0, 1.8). According to the generalized additive model (GAM), we found that lnLAP was positively correlated with baPWV and baPWV elevation. The results were the same for males and females. Subgroup analyses showed that the positive correlation between lnLAP and elevated baPWV did not interact across all subgroups. Conclusions: In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.