WenTongGanPi Decoction Alleviates Diarrhea-predominant Irritable Bowel Syndrome by Improving Intestinal Barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: WenTongGanPi Decoction (WTGPD) is a representative medical practice of the Fuyang School of Traditional Chinese Medicine (TCM), which originated from the classical Lu's Guizhi method. WTGPD places emphasis on the balance and functionality of yang qi, and is effective in treating TCM symptoms related to liver qi stagnation and spleen yang deficiency. In TCM, diarrhea-predominant irritable bowel syndrome (IBS-D) is often diagnosed as liver depression and spleen deficiency, and the use of WTGPD has shown significant therapeutic effect. However, the underlying mechanism of WTGPD treating IBS-D remains unclear. AIM OF THE STUDY: To explore the effect and mechanism of WTGPD in the treatment of IBS-D. MATERIALS AND METHODS: An IBS-D model with liver depression and spleen deficiency was constructed by chronic immobilization stress stimulation and sennae folium aqueous lavage. The impact of WTGPD on IBS-D rats was evaluated through measurements of body weight, fecal water content, and abdominal withdrawal reflex (AWR). Intestinal permeability was assessed using hematoxylin-eosin (HE), alcian blue-periodic acid Schiff (AB-PAS), immunofluorescence (IF) staining, and quantitative real-time PCR (qRT-PCR). The components of WTGPD were analyzed using UPLC-Q-TOF-MS. The underlying mechanisms were investigated through network pharmacology, transcriptomics sequencing, Western blot (WB), molecular docking, and 16S rRNA sequencing. RESULTS: WTGPD treatment effectively alleviated diarrhea and abnormal pain in IBS-D rats (P<0.05). It enhanced the intestinal barrier function by improving colonic structure and increasing the expression of tight junction proteins (P<0.05). A total of 155 components were identified in WTGPD. Both network pharmacology and transcriptomics sequencing analysis highlighted MAPK as the key signaling pathway in WTGPD's anti-IBS-D effect. The WB results showed a significant decrease in p-p38, p-ERK and p-JNK expression after WTGPD treatment (P<0.0001). Guanosine, adenosine and hesperetin in WTGPD may be involved in regulating the phosphorylation of p38, ERK and JNK. Additionally, WTGPD significantly enhanced microbial diversity and increased the production of colonic valeric acid in IBS-D rats (P<0.01). CONCLUSION: In conclusion, our findings suggest that WTGPD can effectively alleviate IBS-D and improve intestinal barrier likely via inhibiting MAPK signal pathway and improving micobial dysbiosis.

Effects of Jasmonic Acid on Stress Response and Quality Formation in Vegetable Crops and Their Underlying Molecular Mechanisms.

The plant hormone jasmonic acid plays an important role in plant growth and development, participating in many physiological processes, such as plant disease resistance, stress resistance, organ development, root growth, and flowering. With the improvement in living standards, people have higher requirements regarding the quality of vegetables. However, during the growth process of vegetables, they are often attacked by pests and diseases and undergo abiotic stresses, resulting in their growth restriction and decreases in their yield and quality. Therefore, people have found many ways to regulate the growth and quality of vegetable crops. In recent years, in addition to the role that JA plays in stress response and resistance, it has been found to have a regulatory effect on crop quality. Therefore, this study aims to review the jasmonic acid accumulation patterns during various physiological processes and its potential role in vegetable development and quality formation, as well as the underlying molecular mechanisms. The information provided in this manuscript sheds new light on the improvements in vegetable yield and quality.

Directional regulation of reactive oxygen species in titanium dioxide boosting the photocatalytic degradation performance of azo dyes.

It has been widely accepted that the generation of reactive oxygen species such as superoxide radical, hydroxyl radical, and hydrogen peroxide during photocatalysis is responsible for the degradation of azo dyes. However, it is unclear which reactive oxygen species primarily contributes to the degradation efficiency of azo dyes. Here, we demonstrate that the directional regulation of reactive oxygen species in titanium dioxide (TiO2) to form superoxide radicals by ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) can significantly improve the degradation performance of methyl orange. The optimized addition of EDTA-2Na can completely degrade azo dyes such as methyl orange, acid orange and alkaline orange at a concentration of 10 mg/L in about 20 min, which is not only higher than that achieved by pristine TiO2 under Xe lamp light but also far superior to the reported degradation efficiency of modified TiO2. Even under natural sunlight, this strategy can also effectively decompose azo dyes, demonstrating the great potential for practical water treatment using low-cost TiO2 photocatalysts.

Recent developments and new directions in the use of natural products for the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) represents a significant global health challenge, and there is an urgent need to explore novel therapeutic interventions. Natural products have demonstrated highly promising effectiveness in the treatment of IBD. PURPOSE: This study systematically reviews the latest research advancements in leveraging natural products for IBD treatment. METHODS: This manuscript strictly adheres to the PRISMA guidelines. Relevant literature on the effects of natural products on IBD was retrieved from the PubMed, Web of Science and Cochrane Library databases using the search terms "natural product," "inflammatory bowel disease," "colitis," "metagenomics", "target identification", "drug delivery systems", "polyphenols," "alkaloids," "terpenoids," and so on. The retrieved data were then systematically summarized and reviewed. RESULTS: This review assessed the different effects of various natural products, such as polyphenols, alkaloids, terpenoids, quinones, and others, in the treatment of IBD. While these natural products offer promising avenues for IBD management, they also face challenges in terms of clinical translation and drug discovery. The advent of metagenomics, single-cell sequencing, target identification techniques, drug delivery systems, and other cutting-edge technologies heralds a new era in overcoming these challenges. CONCLUSION: This paper provides an overview of current research progress in utilizing natural products for the treatment of IBD, exploring how contemporary technological innovations can aid in discovering and harnessing bioactive natural products for the treatment of IBD.

MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.

Bone cancer pain (BCP), due to cancer bone metastasis and bone destruction, is a common symptom of tumors, including breast, prostate, and lung tumors. Patients often experience severe pain without effective treatment. Here, using a mouse model of bone cancer, we report that MOTS-c, a novel mitochondrial-derived peptide, confers remarkable protection against cancer pain and bone destruction. Briefly, we find that the plasma level of endogenous MOTS-c is significantly lower in the BCP group than in the sham group. Accordingly, intraperitoneal administration of MOTS-c robustly attenuates bone cancer-induced pain. These effects are blocked by compound C, an AMPK inhibitor. Furthermore, MOTS-c treatment significantly enhances AMPKα 1/2 phosphorylation. Interestingly, mechanical studies indicate that at the spinal cord level, MOTS-c relieves pain by restoring mitochondrial biogenesis, suppressing microglial activation, and decreasing the production of inflammatory factors, which directly contribute to neuronal modulation. However, in the periphery, MOTS-c protects against local bone destruction by modulating osteoclast and immune cell function in the tumor microenvironment, providing long-term relief from cancer pain. Additionally, we find that chronic administration of MOTS-c has little effect on liver, renal, lipid or cardiac function in mice. In conclusion, MOTS-c improves BCP through peripheral and central synergistic effects on nociceptors, immune cells, and osteoclasts, providing a pharmacological and biological rationale for the development of mitochondrial peptide-based therapeutic agents for cancer-induced pain.

Tough, Freeze-Resistant, Pressure-Response Gel Polymer Electrolytes with Redox Pairs for Flexible Supercapacitors.

Gel polymer electrolytes are an indispensable part of flexible supercapacitors, since their various characteristics determine the device performance. Here, a composite gel electrolyte (FLPS) mainly consisting of polyvinyl alcohol (PVA), sodium alginate (SA), K3Fe(CN)6/K4Fe(CN)6, and LiCl is rationally designed, in which PVA and SA form a robust three-dimensional network, the redox pair of K3Fe(CN)6/K4Fe(CN)6 serves as a cross-linking agent with SA and even donates the oxidation-reduction reaction from the Fe3+/Fe2+ couple with additional capacitance for the device, and LiCl functions as an ion carrier and a water-retaining salt to improve the long-term stability of FLPS. Thus, the FLPS-based supercapacitor exhibits superior electrochemical characteristics, displaying impressive pseudocapacitance across all current densities and excellent cycling stability (∼99.07% of capacitance retention after 10,000 cycles). Moreover, the FLPS-based supercapacitor demonstrates great low-temperature working ability and pressure responsiveness, suggesting its freeze-resistance, flexibility, and pressure sensing potential. This work provides a promising strategy for preparing tough gel polymer electrolytes with both ion transfer and charge storage ability.

Implementing a soil ammonium N fertilizer management for synchronizing potato N demands.

Potatoes, as a high-nitrogen (N)-demand crop, are strongly influenced by both the quantity and form of N supply. Previous studies have demonstrated that applying nitrate N prior to tuber formation and ammonium N post-tuber formation can substantially enhance potato yields and improve N fertilizer use efficiency. However, the ammonium N introduced into the soil undergoes nitrification, creating challenges in aligning the N supply form with the needs of potatoes. This study explored novel N regulation strategies aimed at augmenting potato yields and improving N fertilizer use efficiency. Two field experiments were conducted from 2020 to 2022. Experiment 1 involved four N gradients, namely no N, 150 kg N ha-1, 300 kg N ha-1, and 450 kg N ha-1. Soil samples were collected regularly to determine the transformation patterns of soil ammonium N during potato growth. Experiment 2 included three N management practices: farmer practice (Con), "nitrate followed by ammonium" with nitrification inhibitor (N-NI), and optimization (the soil ammonium N transformation-based split application of N fertilizer, Opt). The potato yield and N fertilizer use efficiency were compared to assess the performance of the optimized strategy. The results showed that 90 % of the ammonium N transformed 20 days after the basal dressing of N. When N fertilizer was applied as top dressing during the tuber formation and bulking stages, more than 90 % of ammonium N was transformed after 10 days. The optimized strategy resulted in a 20 % increase in potato yield, a 20 % increase in N fertilizer partial factor productivity, and a 12-20 % reduction in residual inorganic N in the 0-60 cm soil layer. This suggests that ammonium N applied as base fertilizer exhibits a relatively slow transformation rate, while applying ammonium N as top dressing during the tuber formation and bulking stages accelerates the transformation rate. The split application of ammonium N based on soil ammonium N transformation patterns can improve the alignment between the N supply form with the specific demands of potatoes.

Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase.

As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.

Multi-scale revealing how real catalyst layer interfaces dominate the local oxygen transport resistance in ultra-low platinum PEMFC.

In view of a catalyst layer (CL) with low-Pt causing higher local transport resistance of O2 (Rlocal), we propose a multi-study methodology that combines CO poisoning, the limiting current density method, and electrochemical impedance spectroscopy to reveal how real CL interfaces dominate Rlocal. Experimental results indicate that the ionomer is not evenly distributed on the catalyst surface, and the uniformity of ionomer distribution does not show a positive correlation with the ionomer content. When the ionomer coverage on the supported catalyst surface is below 20 %, the ECSA is only 10 m2·g-1, and the ionomer coverage on the supported catalyst surface reaches 60 %, the ECSA is close to 40 m2·g-1. The ECSA has a positive correlation with ionomer coverage. Because the ECSA is measured by CO poisoning, it can be inferred that the platinum contacted with ionomer can generate effective active sites. Furthermore, a more uniform distribution of ionomer can create additional proton transport channels and reduce the distance for oxygen transport from the catalyst layer bulk to the active sites. A higher ECSA and a shorter distance for oxygen transport will reduce the Rlocal, leading to better performance.

Description of a pathogenic strain of Aeromonas dhakensis isolated from Ancherythroculter nigrocauda in an inland region of China.

Aeromonas dhakensis is reported as an emerging pathogenic species within the genus Aeromonas and is widely distributed in tropical coastal areas. This study provided a detailed description and characterization of a strain of A. dhakensis (202108B1) isolated from diseased Ancherythroculter nigrocauda in an inland region of China. Biochemical tests identified the isolate at the genus level, and the further molecular analysis of concatenated housekeeping gene sequences revealed that the strain belonged to the species A. dhakensis. The isolated A. dhakensis strain was resistant to five antibiotics, namely, penicillin, ampicillin, clindamycin, cephalexin, and imipenem, while it was susceptible to or showed intermediate resistance to most of the other 15 tested antibiotics. The isolated strain of A. dhakensis caused acute hemorrhagic septicemia and tissue damage in artificially infected A. nigrocauda, with a median lethal dose of 7.76 × 104 CFU/fish. The genome size of strain 202108B1 was 5 043 286 bp, including 1 chromosome and 4 plasmids. This is the first detailed report of the occurrence of infection caused by an A. dhakensis strain causing infection in an aquaculture system in inland China, providing important epidemiological data on this potential pathogenic species.

Weighted gene co-expression network analysis reveals key biomarkers and immune infiltration characteristics for bronchial epithelial cells from asthmatic patients.

BACKGROUND: Asthma ranks among the most prevalent non-communicable diseases worldwide. Previous studies have elucidated the significant role of the immune system in its pathophysiology. Nevertheless, the immune-related mechanisms underlying asthma are complex and still inadequately understood. Thus, our objective was to investigate novel key biomarkers and immune infiltration characteristics associated with asthma by employing integrated bioinformatics tools. METHODS: In this study, we conducted a weighted gene co-expression network analysis (WGCNA) to identify key modules and genes potentially implicated in asthma. Functional annotation of these key modules and genes was carried out through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, we constructed a protein-protein interaction (PPI) network using the STRING database to identify 10 hub genes. Furthermore, we evaluated the relative proportion of immune cells in bronchial epithelial cell samples from 20 healthy individuals and 88 asthmatic patients using CIBERSORT. Finally, we validated the hub genes and explored their correlation with immune infiltration. RESULTS: Furthermore, 20 gene expression modules and 10 hub genes were identified herein. Among them, complement component 3 (C3), prostaglandin I2 receptor (PTGIR), parathyroid hormone-like hormone (PTHLH), and C-X3-C motif chemokine ligand 1 (CX3CL1) were closely correlated with the infiltration of immune cells. They may be novel candidate biomarkers or therapeutic targets for asthma. Furthermore, B cells memory, and plasma cells might play an important role in immune cell infiltration after asthma. CONCLUSIONS: C3, PTGIR, CX3CL1, and PTHLH have important clinical diagnostic values and are correlated with infiltration of multiple immune cell types in asthma. These hub genes, B cells memory, and plasma cells may become important biological targets for therapeutic asthma drug screening and drug design.

A Dielectric MXene-Induced Self-Built Electric Field in Polymer Electrolyte Triggering Fast Lithium-Ion Transport and High-Voltage Cycling Stability.

Quasi-solid polymer electrolyte (QPE) lithium (Li)-metal battery holds significant promise in the application of high-energy-density batteries, yet it suffers from low ionic conductivity and poor oxidation stability. Herein, a novel self-built electric field (SBEF) strategy is proposed to enhance Li+ transportation and accelerate the degradation dynamics of carbon-fluorine bond cleavage in LiTFSI by optimizing the termination of MXene. Among them, the SBEF induced by dielectric Nb4C3F2 MXene effectively constructs highly conductive LiF-enriched SEI and CEI stable interfaces, moreover, enhances the electrochemical performance of the QPE. The related Li-ion transfer mechanism and dual-reinforced stable interface are thoroughly investigated using ab initio molecular dynamics, COMSOL, XPS depth profiling, and ToF-SIMS. This comprehensive approach results in a high conductivity of 1.34 mS cm-1, leading to a small polarization of approximately 25 mV for Li//Li symmetric cell after 6000 h. Furthermore, it enables a prolonged cycle life at a high voltage of up to 4.6 V. Overall, this work not only broadens the application of MXene for QPE but also inspires the great potential of the self-built electric field in QPE-based high-voltage batteries.

The loss of plant functional groups increased arthropod diversity in an alpine meadow on the Tibetan Plateau.

Plant species loss, driven by global changes and human activities, can have cascading effects on other trophic levels, such as arthropods, and alter the multitrophic structure of ecosystems. While the relationship between plant diversity and arthropod communities has been well-documented, few studies have explored the effects of species composition variation or plant functional groups. In this study, we conducted a long-term plant removal experiment to investigate the impact of plant functional group loss (specifically targeting tall grasses and sedges, as well as tall or short forbs) on arthropod diversity and their functional groups. Our findings revealed that the removal of plant functional groups resulted in increased arthropod richness, abundance and the exponential of Shannon entropy, contrary to the commonly observed positive correlation between plant diversity and consumer diversity. Furthermore, the removal of different plant groups had varying impacts on arthropod trophic levels. The removal of forbs had a more pronounced impact on herbivores compared to graminoids, but this impact did not consistently cascade to higher-trophic arthropods. Notably, the removal of short forbs had a more significant impact on predators, as evidenced by the increased richness, abundance, the exponential of Shannon entropy, inverse Simpson index and inverse Berger-Parker index of carnivores and abundance of omnivores, likely attributable to distinct underlying mechanisms. Our results highlight the importance of plant species identity in shaping arthropod communities in alpine grasslands. This study emphasizes the crucial role of high plant species diversity in controlling arthropods in natural grasslands, particularly in the context of plant diversity loss caused by global changes and human activities.

Learning Stiffness Tensors in Self-Activated Solids via a Local Rule.

Mechanical metamaterials are often designed with particular properties for specific load-bearing functions. Alternatively, this study aims to create a class of active lattice metamaterials, dubbed self-activated solids, that can learn desired stiffness tensors from the elastic deformations they experienced, a crucial feature to improve the performance, efficiency, and functionality of materials. Artificial adaptive matters that combine sensory, control, and actuation elements can offer appealing solutions. However, challenges still remain: The designs will rely on accurate off-line and global computations, as well as intricate coordination among individual elements. Here, a simple online and local learning strategy is initiated based on contrastive Hebbian learning to gradually guide self-activated solids to possess sought-after stiffness tensors autonomously and reversibly. During learning, the bond stiffness of the active lattice varies depending only on its local strain. The numerical tests show that the self-activated solid can not only achieve the desired bulk, shear, and coupling moduli but also manifest uni-mode and bi-mode extremal materials by itself after experiencing the corresponding elastic deformations. Further, the self-activated solid can also achieve the desired time-varying moduli when exposed to temporally different loads. The design is applicable to any lattice geometries and is resistant to damage and instabilities. The material design approach and the physical learning strategy suggested can benefit the design of autonomous materials, physical learning machines, and adaptive robots.

The roles of autophagy in the treatment of diabetic nephropathy with rapamycin.

BACKGROUND: Rapamycin is known to induce autophagy, promote cell survival and inhibit the progression of diabetic nephropathy (DN). OBJECTIVES: The aim of this study was to examine the role of autophagy in the treatment of DN with rapamycin to provide the basis for the DN treatment with rapamycin. MATERIAL AND METHODS: Human mesangial cells (HMC) were cultured in a constant temperature incubator with 5% CO2, at 37°C and saturated humidity. Cells were divided into 5 groups and the 5-ethynyl-2-deoxyuridine (EdU) cell proliferation assay was used to determine cell proliferation. Flow cytometry was used to determine cell apoptosis, while GFP-RFP-LC3 showed autophagy flow. Western blot was employed to detect the expression of autophagy-related proteins LC3-II/LC3-I and P62. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of type IV collagen fiber (Col4), hyaluronic acid (HA) and laminin (LA) in the extracellular matrix (ECM). RESULTS: Cell proliferation was the lowest in the hyperglycemic group. Additionally, the hyperglycemic group displayed the lowest number of autolysosomes compared to other groups. In contrast, the rapamycin group exhibited the highest number of autolysosomes. The LC3-II/LC3-I ratio was also the lowest in the hyperglycemic group, measuring 0.53 (0.50-0.58), while the expression level of P62 was significantly higher in that group at 0.98 (0.95-1.01) compared to other groups. Upon the introduction of rapamycin, the LC3-II/LC3-I ratio was significantly increased at 2.21 (1.95-2.21), and P62 was significantly decreased 0.38 (0.38-0.39) compared to the hyperglycemic group. Both changes were statistically significant, with p-values of 0.034 and 0.010, respectively. Enzyme-linked immunosorbent assay was employed to detect Col4, HA and LA content. The study findings demonstrated significantly higher levels of glucose in the hyperglycemic group in comparison to other groups. In contrast, the rapamycin group exhibited significantly lower levels of glucose than the hyperglycemic group, yet the difference was not statistically significant. CONCLUSIONS: Hyperglycemic can inhibit the autophagic activity of HMC, promote cell apoptosis, enhance ECM accumulation, and facilitate the DN progression. In contrast, rapamycin can elicit autophagy, decrease mesangial matrix proliferation, and therefore impede DN progression.

Contiguous identity between entire coding regions of transgenic and native genes rather than special regions is essential for a strong co-suppression.

The discovery of co-suppression in plants has greatly boosted the study of gene silencing mechanisms, but its triggering mechanism has remained a mystery. In this study, we explored its possible trigger mechanism by using Fatty acid desaturase 2 (FAD2) and Fatty acid elongase 1 (FAE1) strong co-suppression systems. Analysis of small RNAs in FAD2 co-suppression lines showed that siRNAs distributed throughout the coding region of FAD2 with an accumulated peak. However, mutations of the peak siRNA-matched site and siRNA derived site had not alleviated the co-suppression of its transgenic lines. Synthetic FAD2 (AtFAD2sm), which has synonymous mutations in the entire coding region, failed to trigger any co-suppression. Furthermore, 5' and 3' portions of AtFAD2 and AtFAD2sm were swapped to form two hybrid genes, AtFAD2-3sm and AtFAD2-5sm. 80 % and 92 % of their transgenic lines exhibited co-suppression, respectively. Finally, FAE1s with different degrees of the continuous sequence identity compared with AtFAE1 were tested in their Arabidopsis transgenic lines, and the results showed the co-suppression frequency was reduced as their continuous sequence identity stepped down. This work suggests that contiguous identity between the entire coding regions of transgenic and native genes rather than a special region is essential for a strong co-suppression.

Biodiversity conservation and management of lake wetlands based on the spatiotemporal evolution patterns of crane habitats.

The typical lake wetlands in the middle and lower reaches of the Yangtze River are important wintering sites of cranes in China. The spatiotemporal evolution of crane populations and their habitats has great value in clarifying the pivotal role of regional lake wetlands in biodiversity conservation. Therefore, 2562 data points of four crane species were selected in this study. The data reflected the distributional position of the cranes over the period 2000-2020. Twelve surrounding environmental factors were selected to investigate the spatiotemporal evolution in the study area by using the MaxEnt model. The Jackknife method was used to identify the main environmental factors affecting the choice of crane habitats. The results indicated that: (1) Developed land in the study area increased by 42,795.81 hm2. The crane populations were mainly distributed in the farmland and mudflat, and their number decreased yearly. (2) From 2000 to 2020, the area of suitable crane habitat experienced an overall decrease. Specifically, the mid-suitable area dwindled by 6234.23 hm2, marking a substantial reduction of 52.05 %. Similarly, the most suitable area saw a decline of 786.41 hm2, representing a noteworthy decrease of 71.09 %. (3) The findings from the analysis of influencing factors revealed a dynamic pattern over the years. Habitat type, water density, and distance to water were the main influencing factors in the study area from 2000 to 2020. This study provides a new perspective on the conservation and structural habitat restoration of crane populations in the middle and lower reaches of the Yangtze River.

Kongensin a attenuates intervertebral disc degeneration by inhibiting TAK1-mediated PANoptosis of nucleus pulposus cells.

Low back pain (LBP) is most commonly caused by intervertebral disc degeneration (IVDD). Pyroptosis, apoptosis, and necroptosis are crucial in IVDD pathogenesis; however, possible simultaneous occurrence in IVDD and co-regulation between the pathways and the regulatory mechanisms have not been investigated. PANoptosis is a regulated cell death (RCD) pathway with the key characteristics of pyroptosis, apoptosis, and necroptosis. This study revealed that tert-butyl hydroperoxide (TBHP) altered the expression of key proteins involved in PANoptosis in nucleus pulposus cells (NPCs). Furthermore, the natural product Kongensin A (KA), which has potential anti-necrotic and anti-inflammatory properties, inhibited PANoptosis. TAK1, often referred to as mitogen-activated protein kinase kinase kinase 7 (Map3k7), is a key regulator of innate immunity, cell death, inflammation, and cellular homeostasis; however, the physiological roles and regulatory mechanisms underlying IVDD remain unclear. In this study, we discovered that KA can upregulate TAK1 expression in NPCs, -which inhibits PANoptosis by suppressing oxidative stress. In conclusion, our results suggest that KA inhibits PANoptosis and delays IVDD progression in NPCs by upregulating TAK1 expression to maintain mitochondrial redox balance. Consequently, targeting TAK1 may be a promising therapeutic approach for IVDD therapy.

TMEM63B channel is the osmosensor required for thirst drive of interoceptive neurons.

Thirst plays a vital role in the regulation of body fluid homeostasis and if deregulated can be life-threatening. Interoceptive neurons in the subfornical organ (SFO) are intrinsically osmosensitive and their activation by hyperosmolarity is necessary and sufficient for generating thirst. However, the primary molecules sensing systemic osmolarity in these neurons remain elusive. Here we show that the mechanosensitive TMEM63B cation channel is the osmosensor required for the interoceptive neurons to drive thirst. TMEM63B channel is highly expressed in the excitatory SFO thirst neurons. TMEM63B deletion in these neurons impaired hyperosmolarity-induced drinking behavior, while re-expressing TMEM63B in SFO restored water appetite in TMEM63B-deficient mice. Remarkably, hyperosmolarity activates TMEM63B channels, leading to depolarization and increased firing rate of the interoceptive neurons, which drives drinking behavior. Furthermore, TMEM63B deletion did not affect sensitivities of the SFO neurons to angiotensin II or hypoosmolarity, suggesting that TMEM63B plays a specialized role in detecting hyperosmolarity in SFO neurons. Thus, our results reveal a critical osmosensor molecule for the generation of thirst perception.

An evaluation of the impact of China's green credit policy on different pathways using a CGE model.

The objective of the study was to quantitatively analyze the heterogeneous effects of different green credit implementation methods on energy, environmental, and economic systems by developing a computable general equilibrium model. The specific green credit implementation methods are divided into interest-penalty policy for energy-intensive industries and interest preferential policy for green industries. Various approaches to implementing green credit can lead to distinct impacts on energy consumption, environmental outcomes, and economic performance. Green credit policy experiments are carried out utilizing short-, medium-, and long-term scenarios to investigate how the consequences of green credit policies evolve. The findings demonstrate that (1) implementing a penalty interest policy for energy-intensive industries can have substantial short-term environmental effects, cutting total demand for fossil energy and lowering carbon dioxide emissions significantly. As the cycle progresses, this effect will progressively fade and have a negative economic impact. (2) The interest preferential policy for the green industry has a significant promoting effect on green technology, and its energy and environmental effects will be reflected in the long term, and the effect will continue to increase, which has a positive promoting effect on the economy. (3) There are significant differences in the policy effects brought about by the different implementation methods of green credit policies. Both policies can positively affect social energy and the environment, but the effect cycles are different. When two types of interest policies are implemented in the economy, the negative economic effect of the penalty interest policy is greater than the positive effect of the preferential interest policy, which harms the macroeconomy. These conclusions will provide theoretical and practical references for the government and banks to choose a better green credit implementation path.