Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System.

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

Distribution characteristics and integrated ecological risks evaluation modelling of microplastics and heavy metals in geological high background soil.

The microplastics (MPs), a novel pollutant, and heavy metals (HMs) significantly affect soil ecology. The study investigated HMs and MPs in Qianxi's high geological background soil, established a model for risk evaluation with MPs types and shapes, and proposed a two-dimensional comprehensive index model for MPs-HMs combined pollution and risk evaluation criterion. The results revealed a high soil Cd concentration, with a mean value of 0.38 mg·kg-1. Additionally, soils from soybean-wheat intercropping-potato-corn rotation (SWI-PCR) exhibited significantly higher concentrations of Hg, As, and Pb compared with those from soybean-wheat intercropping-corn rotation (SWI-CR). Moreover, the soil exhibited a high abundance of MPs (8667.66 ± 3864.26 items·kg-1), mainly characterized by PS and fiber. The mean of adjusted ecological risk index (ARI) for MPs in soil was 525.27, indicating a grade 3 risk. The two-dimensional combined index (TPI) was used to assess the ecological risk of MPs-HMs combined pollution, exhibiting an exceedance rate of 56 % with a mean of 445.07. The risk level of the combined pollution was graded as 6, indicating high risk. The microplastic risk evaluation model and the comprehensive evaluation method of combined pollution established in this study provide a reference for the future risk evaluation of multi-pollutant combined pollution.

A potential early-atheroprotective target: Irgm1 mediates lymphangiogenesis through LEC autophagy by Tfeb translocation.

Lymphatic dysfunction is a pivotal pathological mechanism underlying the development of early atherosclerotic plaques. Potential targets of lymphatic function must be identified to realize the early prevention and treatment of atherosclerosis (AS). The immunity-related GTPase Irgm1 is involved in orchestrating cellular autophagy and apoptosis. However, the effect of Irgm1 on early AS progression, particularly through alterations in lymphatic function, remains unclear. In this study, we confirmed the protective effect of lymphangiogenesis on early-AS in vivo. Subsequently, an in vivo model of early AS mice with Irgm1 knockdown shows that Irgm1 reduces early atherosclerotic plaque burden by promoting lymphangiogenesis. Given that lymphatic endothelial cell (LEC) autophagy significantly contributes to lymphangiogenesis, Irgm1 may enhance lymphatic circulation by promoting LEC autophagy. Moreover, Irgm1 orchestrates autophagy in LECs by inhibiting mTOR and facilitating nuclear translocation of Tfeb. Collectively, these processes lead to lymphangiogenesis. Thus, this study establishes a link between Irgm1 and early AS, thus revealing a novel mechanism by which Irgm1 exerts an early protective influence on AS within the context of lymphatic circulation. The insights gained from this study have the potential to revolutionize the approach and management of AS onset.

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil-Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

Scrophularia ningpoensis Hemsl. holds a prominent place among Chinese medicinal herbs. Assessing the soil-plant system of its origin is crucial for ensuring medication safety. Although some trace elements are essential for the normal functioning of living organisms, exposure to higher concentrations is harmful to humans, so in order to assess the possible health risk of trace elements in the soil-plant system of Scrophularia ningpoensis Hemsl. origin for human assessment, we used non-carcinogenic risk (HI) and carcinogenic risk (CR) for their evaluation. In this paper, the following trace elements were studied in the soil-Scrophularia ningpoensis Hemsl. system: manganese (Mn), iron (Fe), cobalt (Co), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As) and lead (Pb). Correlation and structural equation analyses showed that the effect of soil in the root zone on the plant was much greater than the effect of soil in the non-root zone on the plant. The single-factor pollution index (Pi) showed that the soil in the production area of Scrophularia ningpoensis Hemsl. was polluted to a certain extent, notably with Pb showing the highest average Pi values of 0.94 and 0.89 in the non-root and root zones, respectively. Additionally, the Nemerow composite pollution indices (PN) for both zones indicated an alert range. Regarding health risks, exposure to soil in the non-root zone posed higher non-carcinogenic risk (HI) and carcinogenic risk (CR) compared to the root zone, although neither zone presented a significant carcinogenic risk. The potential non-carcinogenic risk (HI) and carcinogenic risk (CR) from consuming Scrophularia ningpoensis Hemsl. leaves and stems were more than ten times higher than that of roots. However, the carcinogenic risk (CR) values for both the soil and plant of interest in the soil- Scrophularia ningpoensis Hemsl. system did not exceed 10-4, and therefore no significant carcinogenic risk existed.

Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy versus Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Disorders: A Meta-Analysis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. METHODS: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. RESULTS: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p<0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p=0.0006) and benign disorder (87.62% vs. 60.00%, p＜0.0001). CONCLUSION: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

Magnetic-assisted preparation and performance control of Fe3O4/PVDF gradient magnetic composites.

In this study, a gradient Fe3O4/PVDF magnetic composite was prepared using magnetic-assisted template filling technology. The purpose of this study was to explore a simple, economical, and scalable method for preparing gradient magnetic composites. The structure and magnetic performance of the composite were studied, and the parameters that influenced the gradient magnetic properties of the material, such as magnetic intensity, magnet spacing, initial content of magnetic particles, and magnet movement speed, were investigated. The results showed that increasing magnetic intensity during the template filling process enhanced the electromagnetic force on the magnetic particles, resulting in a greater magnetic particle content gradient. The variation in magnet spacing affected the spatial magnetic field distribution, and increasing the magnet spacing increased the gradient of the magnetic intensity in the y-direction. The magnetic gradient of the Fe3O4/PVDF composite first decreased and then increased as the magnet spacing increased. Increasing the magnet movement speed enhanced the gradient of the magnetic intensity in the y-component but shortened the duration of the electromagnetic force. By adjusting these parameters, it is possible to regulate the structural and magnetic properties of the Fe3O4/PVDF composite. This work may have implications for research and application in related fields and promote the development and innovation of magnetic materials.

Effects of soil properties and land use patterns on the distribution of microplastics: A case study in southwest China.

Microplastic pollution in the soil environment is of great concern. However, the current research on microplastics (MPs) in Southwest China mainly focuses on their distribution characteristics and sources in soil, making the understanding of the soil properties and land use patterns influencing soil MPs insufficient. In this study, the abundance and distribution characteristics of MPs in the soil of different land use patterns in Guizhou Province were determined. The results revealed that the average abundance of MPs in soils was 2936 items/kg, ranging from 780 to 9420 items/kg. The MPs were mainly small particle size (0-0.5 mm), granular, and black, accounting for 87.5%, 36.6%, and 82.2%, respectively. The most common polymer types of MPs were polypropylene, polyethylene terephthalate, and polyethylene, which accounted for 20.4%, 16.8%, and 16.4%, respectively. As soil bulk density increased, microplastic abundance and small particle size decreased. Soil microplastic abundance slightly decreased with increasing soil porosity. The abundance of MPs increased with the increase in soil pH, but no significant correlation was observed between soil organic matter content and microplastic abundance. pH was the major factor that affected the microplastic distribution, which accounted for 32.5%. This study provides insight into the distribution and influencing factors of soil MPs and also provides a theoretical basis for subsequent research on soil microplastic pollution.

PSTPIP2 ameliorates aristolochic acid nephropathy by suppressing interleukin-19-mediated neutrophil extracellular trap formation.

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by herbal medicines. Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) and neutrophil extracellular traps (NETs) play important roles in kidney injury and immune defense, respectively, but the mechanism underlying AAN regulation by PSTPIP2 and NETs remains unclear. We found that renal tubular epithelial cell (RTEC) apoptosis, neutrophil infiltration, inflammatory factor, and NET production were increased in a mouse model of AAN, while PSTPIP2 expression was low. Conditional knock-in of Pstpip2 in mouse kidneys inhibited cell apoptosis, reduced neutrophil infiltration, suppressed the production of inflammatory factors and NETs, and ameliorated renal dysfunction. Conversely, downregulation of Pstpip2 expression promoted kidney injury. In vivo, the use of Ly6G-neutralizing antibody to remove neutrophils and peptidyl arginine deiminase 4 (PAD4) inhibitors to prevent NET formation reduced apoptosis, alleviating kidney injury. In vitro, damaged RTECs released interleukin-19 (IL-19) via the PSTPIP2/nuclear factor (NF)-κB pathway and induced NET formation via the IL-20Rß receptor. Concurrently, NETs promoted apoptosis of damaged RTECs. PSTPIP2 affected NET formation by regulating IL-19 expression via inhibition of NF-κB pathway activation in RTECs, inhibiting RTEC apoptosis, and reducing kidney damage. Our findings indicated that neutrophils and NETs play a key role in AAN and therapeutic targeting of PSTPIP2/NF-κB/IL-19/IL-20Rß might extend novel strategies to minimize Aristolochic acid I-mediated acute kidney injury and apoptosis.

Aristolochic acid nephropathy (or AAN for short) is a serious condition affecting the kidneys that is caused by certain traditional Chinese medicines containing a compound called aristolochic acid. This compound is known to have harmful effects on kidney tubular epithelial cells, causing increased inflammation and a form of controlled cell death called apoptosis, which can ultimately lead to organ failure. There is currently no effective treatment for AAN, highlighting the need for a deeper understanding of the mechanisms responsible. Previous studies have shown that immune cells called neutrophils infiltrate the kidneys and damage cells in the early stages of AAN. Neutrophils produce web-like structures called neutrophil extracellular traps, which have been identified as potentially contributing to the damage. A protein called PSTPIP2, which regulates inflammation, has also been shown to contribute to other types of kidney injury. To understand how these inflammatory factors might be involved in AAN, Du, Xu et al. genetically engineered mice to produce extra PSTPIP2 protein specifically in their kidneys. When given aristolochic acid, these mice displayed less kidney damage. Further studies of mouse kidney cells showed that PSTPIP2 protects the kidney by suppressing an inflammatory mechanism that leads to the production of neutrophil extracellular traps. By contrast, in models where PSTPIP2 levels were reduced, neutrophil extracellular traps were shown to cause both apoptosis and kidney injury. The findings of Du, Xu et al. show that neutrophil extracellular traps cause cell damage and apoptosis in a mouse model of AAN and that this action can be reduced by increasing the levels of the protein PSTPIP2. This sheds light on the inflammatory mechanisms behind the kidney damage caused by herbal medicines containing aristolochic acid. Additionally, it opens new avenues for studies aiming to find ways to treat AAN, suggesting that targeting PSTPIP2 could be a promising strategy.

Arterial Stiffness and Obesity as Predictors of Diabetes: Longitudinal Cohort Study.

BACKGROUND: Previous studies have confirmed the separate effect of arterial stiffness and obesity on type 2 diabetes; however, the joint effect of arterial stiffness and obesity on diabetes onset remains unclear. OBJECTIVE: This study aimed to propose the concept of arterial stiffness obesity phenotype and explore the risk stratification capacity for diabetes. METHODS: This longitudinal cohort study used baseline data of 12,298 participants from Beijing Xiaotangshan Examination Center between 2008 and 2013 and then annually followed them until incident diabetes or 2019. BMI (waist circumference) and brachial-ankle pulse wave velocity were measured to define arterial stiffness abdominal obesity phenotype. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% CI. RESULTS: Of the 12,298 participants, the mean baseline age was 51.2 (SD 13.6) years, and 8448 (68.7%) were male. After a median follow-up of 5.0 (IQR 2.0-8.0) years, 1240 (10.1%) participants developed diabetes. Compared with the ideal vascular function and nonobese group, the highest risk of diabetes was observed in the elevated arterial stiffness and obese group (HR 1.94, 95% CI 1.60-2.35). Those with exclusive arterial stiffness or obesity exhibited a similar risk of diabetes, and the adjusted HRs were 1.63 (95% CI 1.37-1.94) and 1.64 (95% CI 1.32-2.04), respectively. Consistent results were observed in multiple sensitivity analyses, among subgroups of age and fasting glucose level, and alternatively using arterial stiffness abdominal obesity phenotype. CONCLUSIONS: This study proposed the concept of arterial stiffness abdominal obesity phenotype, which could improve the risk stratification and management of diabetes. The clinical significance of arterial stiffness abdominal obesity phenotype needs further validation for other cardiometabolic disorders.

Electrochemical Radical Retro-Allylation of Homoallylic Alcohols with Sulfonyl Hydrazides.

We report herein the first examples of electrochemical radical retro-allylation of homoallylic alcohols via the cleavage of the C(sp3)-C(sp3) bond. In this reaction, a variety of sulfonyl hydrazides were employed as the environmentally friendly radical sources via an electrochemical dehydrazination with the release of N2 and H2 as the byproducts, leading to sulfonyl allylic compounds in moderate to good yields. The reaction features metal- and base-free reaction conditions, broad functional group tolerance, and a broad substrate scope.

Evaluation of niche, diversity, and risks of microplastics in farmland soils of different rocky desertification areas.

The occurrence, sources, effects, and risks of microplastics (MPs) in farmland soils have attracted considerable attention. However, the pollution and ecological characteristics of MPs in farmland soils at different levels of rocky desertification remain unclear. We collected and analyzed farmland soil samples from rocky desertification areas in Guizhou, China, ranging from no to heavy risks. We explored differences and migration of MPs across these areas, unveiled the relationship between diversity, niche, and risks of MPs, and determined influencing factors. The average abundance of soil MPs was 8721 ± 3938 item/kg, and the abundance and contamination factor (CF) of MPs escalated with the increase in rocky desertification level. Diversity, niche, and risk of soil MPs in different rocky desertification areas were significantly different. Rocky desertification caused both MP community differences and linked MP communities at different sites. Diversity and niche significantly affected MP risk (p < 0.05). Environmental factors with significant correlations (p < 0.05) with the abundance and ecological characteristics of MPs varied significantly in soils of different rocky desertification areas. This study advances our comprehension of MP pollution in farmland soils within rocky desertification areas, offering essential data and theoretical insights for the development of control strategies.

Microplastics in Qinghai-Tibet Plateau and Yunnan-Guizhou Plateau lakes, China.

As an emerging environmental pollutant, microplastics (MPs) have received widespread attention. Recently, studies examining microplastic pollution in plateau lakes have been increasing, but few have examined the distributions, sources, and fates of MPs in different plateau areas. In this work, the abundances and characteristics of MPs in surface waters and sediments in lakes of the Qinghai-Tibet Plateau (QTP) and Yunnan-Guizhou Plateau (YGP) were systematically investigated. The abundances of MPs in the lakes of the QTP ranges within 0.05-1.8 n/L in surface waters and 10-2643.7 n/kg in sediments. In the lakes of the YGP, the abundances of MPs ranged within 1.3-10.1 n/L in surface waters and 171.7-4260 n/kg in sediments. The dominant shape, color, and size class of MPs were fiber, transparent, and 0-0.5 mm in plateau lakes, respectively. MPs were mainly composed of polypropylene, polyethylene, and polyethylene terephthalate polymers. The different sources of MPs in the QTP and YGP lakes were mainly due to differences in human activities. The primary sources of microplastic pollution in the lakes of the QTP were tourism and atmospheric transport, while sewage discharge, agriculture, and fishing activities were the main sources of MPs in urban lakes of the YGP. Although the level of microplastic pollution in plateau lakes was relatively low, the sources should be identified and monitored so that the effects and extent of microplastic pollution in these fragile environments can be fully understood. This study provides a valuable dataset and theoretical basis for subsequent research on microplastic pollution in plateau lakes.

Mitochondria-derived methylmalonic acid aggravates ischemia-reperfusion injury by activating reactive oxygen species-dependent ferroptosis.

Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia-reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation.

Histone deacetylase-mediated silencing of PSTPIP2 expression contributes to aristolochic acid nephropathy-induced PANoptosis.

BACKGROUND AND PURPOSE: Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by using herbal medicines. Currently, no therapies are available to treat or prevent aristolochic acid nephropathy. Histone deacetylase (HDAC) plays a crucial role in the development and progression of renal disease. We tested whether HDAC inhibitors could prevent aristolochic acid nephropathy and determined the underlying mechanism. EXPERIMENTAL APPROACH: HDACs expression in the aristolochic acid nephropathy model was examined. The activation of PANoptosis of mouse kidney and renal tubular epithelial cell were assessed after exposure to HDAC1 and HDAC2 blockade. Kidney-specific knock-in of proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) mice were used to investigate whether PSTPIP2 affected the production of PANoptosome. KEY RESULTS: Aristolochic acid upregulated the expression of HDAC1 and HDAC2 in the kidneys. Notably, the HDAC1 and HDAC2 specific inhibitor, romidepsin (FK228, depsipeptide), suppressed aristolochic acid-induced kidney injury, epithelial cell pyroptosis, apoptosis and necroptosis (PANoptosis). Moreover, romidepsin upregulated PSTPIP2 in renal tubular epithelial cells, which was enhanced by aristolochic acid treatment. Conditional knock-in of PSTPIP2 in the kidney protected against aristolochic acid nephropathy. In contrast, the knockdown of PSTPIP2 expression in PSTPIP2-knock-in mice restored kidney damage and PANoptosis. PSTPIP2 function was determined in vitro using PSTPIP2 knockdown or overexpression in mouse renal tubular epithelial cells (mTECs). Additionally, PSTPIP2 was found to regulate caspase 8 in aristolochic acid nephropathy. CONCLUSION AND IMPLICATIONS: HDAC-mediated silencing of PSTPIP2 may contribute to aristolochic acid nephropathy. Hence, HDAC1 and HDAC2 specific inhibitors or PSTPIP2 could be valuable therapeutic agents for preventing aristolochic acid nephropathy.

Identification and visualization of environmental microplastics by Raman imaging based on hyperspectral unmixing coupled machine learning.

Microplastics (MPs) are ubiquitous contaminants that have become an emerging pollutant of concern, potentially threatening human health and ecosystem environments. Although current detection methods can accurately identify various types of MPs, it remains necessary to develop non-destructive and rapid methods to meet growing demands for detection. Herein, we combine a hyperspectral unmixing method and machine learning to analyse Raman imaging data of environmental MPs. Five MPs types including poly(butylene adipate-co-terephthalate) (PBAT), poly(butylene succinate) (PBS), p-polyethylene (PE), polystyrene (PS) and polypropylene (PP) were visualized and identified. Individual or mixed pure or aged MPs along with environmental samples were analysed by Raman imaging. Alternating volume maximization (AVmax) combined with unconstrained least squares (UCLS) method estimated end members and abundance maps of each of the MPs in the samples. Pearson correlation coefficients (r) were used as the evaluation index; the results showed that there is a high similarity between the raw spectra and the average spectra calculated by AVmax. This indicates that Raman imaging based on machine learning and hyperspectral unmixing is a novel imaging analysis method that can directly identify and visualize MPs in the environment.

Coastal distribution and driving factors for blue carbon fractions in the surface soil of a warm-temperate salt marsh in China.

A better understanding of blue carbon (BC) sequestration can not only contribute to a better elucidation of global carbon cycle processes but can also lay the foundation for the incorporation of BC ecosystems into regional and global carbon offset schemes. In this study, the surface soils of seven plots along a landward to seaward distance gradient were analyzed for the concentrations and stocks of soil organic carbon (SOC), soil inorganic carbon (SIC), dissolved organic carbon (DOC), and dissolved inorganic carbon (DIC), as well as soil physical (bulk density, texture, moisture), chemical (pH, electrical conductivity), and microbiological (phospholipid fatty acid) properties in the coastal wetlands. Correlation, variation partition and random forest (RF) analyses were used to identify key variables correlating with BC fraction distribution patterns. The results suggested that SIC, DIC, and DOC, exhibited similar landward-increasing trends but the driving factors were distinct from each other. Based on correlation and RF analysis, both SIC and DIC were closely related to soil moisture and clay contents, but microbial indicators of arbuscular mycorrhizal fungi and actinomycete, were found to be associated with SIC, and abiotic properties played less important but still substantial roles in predicting DIC dynamics. In contrast with the other three investigated BC fractions, SOC showed a slight tendency toward enrichment in the seaward direction, and SIC was identified as the main driving factor. DOC showed no significant correlations with the other BC fractions, and its variation could not be explained well by the selected edaphic parameters. The soils in the YRD's tidal Suaeda salsa salt marshes showed a significant negative coupled SOC-SIC correlation, which was potentially related to divergent sedimentary processes and potential biotransformation between SOC and SIC. These results highlight the importance of integrating multiple BC fractions and their interactions into attempts to explore key mechanisms of BC cycling.

Diabetes, glycemic control and arterial stiffness: a real-world cohort study in the context of predictive, preventive, and personalized medicine.

Background: Arterial stiffness is a major contributor to morbidity and mortality worldwide. Although several metabolic markers associated with arterial stiffness have been developed, there is limited data regarding whether glycemic control modifies the association between diabetes and arterial stiffness. For these reasons, identification of traits around diabetes will directly contribute to arterial stiffness and atherosclerosis management in the context of predictive, preventive, and personalized medicine (PPPM). Thus, this study aimed to explore the relationship of diabetes and glycemic control status with arterial stiffness in a real-world setting. Methods: Data of participants from Beijing Xiaotangshan Examination Center (BXEC) with at least two surveys between 2008 and 2019 were used. Cumulative hazards were presented by inverse probability of treatment weighted (IPTW) Kaplan-Meier curves. Cox models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s. Results: Of 5837 participants, the mean baseline age was 46.5±9.3 years, including 3791 (64.9%) males. During a median follow-up of 4.0 years, 1928 (33.0%) cases of incident arterial stiffness were observed. People with diabetes at baseline had a 48.4% (HR: 1.484, 95% CI: 1.250-1.761) excessive risk of arterial stiffness. Adherence to good glycemic control attenuated the relationship between diabetes and arterial stiffness (HR: 1.264, 95% CI: 0.950-1.681); while uncontrolled diabetes was associated with the highest risk of arterial stiffness (HR: 1.629, 95% CI: 1.323-2.005). Results were consistent using IPTW algorithm and multiple imputed data. Conclusion: Our study quantified that diabetes status is closely associated with an increased risk of arterial stiffness and supported that adherence to good glycemic control could attenuate the adverse effect of diabetes on arterial stiffness. Therefore, glucose monitoring and control is a cost-effective strategy for the predictive diagnostics, targeted prevention, patient stratification, and personalization of medical services in early vascular damages and arterial stiffness. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00347-z.

Soil Water Deficit Reduced Root Hydraulic Conductivity of Common Reed (Phragmites australis).

Alterations in root hydraulics in response to varying moisture conditions remain a subject of debate. In our investigation, we subjected common reeds (Phragmites australis) to a 45-day treatment with four distinct soil moisture levels. The findings unveiled that, in response to drought stress, the total root length, surface area, volume, and average diameter exhibited varying degrees of reduction. Anatomically, drought caused a reduction in root diameter (RD), cortex thickness (CT), vessel diameter (VD), and root cross-sectional area (RCA). A decrease in soil moisture significantly reduced both whole- and single-root hydraulic conductivity (Lpwr, Lpsr). The total length, surface area, volume, and average diameter of the reed root system were significantly correlated with Lpwr, while RD, CT, and RCA were significantly correlated with Lpsr. A decrease in soil moisture content significantly influenced root morphological and anatomical characteristics, which, in turn, altered Lpr, and the transcriptome results suggest that this may be associated with the variation in the expression of abscisic acid (ABA) and aquaporins (AQPs) genes. Our initial findings address a gap in our understanding of reed hydraulics, offering fresh theoretical insights into how herbaceous plants respond to external stressors.