Counterion docking: a general approach to reducing energetic disorder in doped polymeric semiconductors.

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.

N-type semiconducting hydrogel.

Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.

Optimized therapeutic potential of Yinchenhao decoction for cholestatic hepatitis by combined network meta-analysis and network pharmacology.

BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.

Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.

Continuous production of ultratough semiconducting polymer fibers with high electronic performance.

Conjugated polymers have demonstrated promising optoelectronic properties, but their brittleness and poor mechanical characteristics have hindered their fabrication into durable fibers and textiles. Here, we report a universal approach to continuously producing highly strong, ultratough conjugated polymer fibers using a flow-enhanced crystallization (FLEX) method. These fibers exhibit one order of magnitude higher tensile strength (>200 megapascals) and toughness (>80 megajoules per cubic meter) than traditional semiconducting polymer fibers and films, outperforming many synthetic fibers, ready for scalable production. These fibers also exhibit unique strain-enhanced electronic properties and exceptional performance when used as stretchable conductors, thermoelectrics, transistors, and sensors. This work not only highlights the influence of fluid mechanical effects on the crystallization and mechanical properties of conjugated polymers but also opens up exciting possibilities for integrating these functional fibers into wearable electronics.

The occurrence of asthma in an extensive-stage small-cell lung cancer patient after combination therapy with atezolizumab and anlotinib: a case report.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events. Case presentation: A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade. Conclusions: This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.

Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

BACKGROUND: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. METHODS: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. RESULTS: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'­adenosine monophosphate­activated protein kinase (p­AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). CONCLUSIONS: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis.

Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence. Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators. Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1ß, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-ß/Smad3. Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD-LF-HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation.

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives.

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/ß-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.

Azonia-Naphthalene: A Cationic Hydrophilic Building Block for Stable N-Type Organic Mixed Ionic-Electronic Conductors.

Conjugated polymers that can efficiently transport both ionic and electronic charges have broad applications in next-generation optoelectronic, bioelectronic, and energy storage devices. To date, almost all the conjugated polymers have hydrophobic backbones, which impedes efficient ion diffusion/transport in aqueous media. Here, we design and synthesize a novel hydrophilic polymer building block, 4a-azonia-naphthalene (AN), drawing inspiration from biological systems. Because of the strong electron-withdrawing ability of AN, the AN-based polymers show typical n-type charge transport behaviors. We find that cationic aromatics exhibit strong cation-π interactions, leading to smaller π-π stacking distance, interesting ion diffusion behavior, and good morphology stability. Additionally, AN enhances the hydrophilicity and ionic-electronic coupling of the polymer, which can help to improve ion diffusion/injection speed, and operational stability of organic electrochemical transistors (OECTs). The integration of cationic building blocks will undoubtedly enrich the material library for high-performance n-type conjugated polymers.

Deciphering the toxicity-effect relationship and action patterns of traditional Chinese medicines from a smart data perspective: a comprehensive review.

In Chinese medicine, the primary considerations revolve around toxicity and effect. The clinical goal is to achieve maximize effect while minimizing toxicity. Nevertheless, both clinical and experimental research has revealed a distinct relationship between these two patterns of action in toxic Traditional Chinese Medicines (TCM). These TCM often exhibit characteristic "double-sided" or "multi-faceted" features under varying pathological conditions, transitioning between effective and toxic roles. This complexity adds a layer of challenge to unraveling the ultimate objectives of Traditional Chinese medicine. To address this complexity, various hypotheses have been proposed to explain the toxicity and effect of Traditional Chinese Medicines. These hypotheses encompass the magic shrapnel theory for effect, the adverse outcome pathway framework, and the indirect toxic theory for toxicity. This review primarily focuses on high-, medium-, and low-toxicity Traditional Chinese Medicines as listed in Chinese Pharmacopoeia. It aims to elucidate the essential intrinsic mechanisms and elements contributing to their toxicity and effectiveness. The critical factors influencing the mechanisms of toxicity and effect are the optimal dosage and duration of TCM administration. However, unraveling the toxic-effect relationships in TCM presents a formidable challenge due to its multi-target and multi-pathway mechanisms of action. We propose the integration of multi-omics technology to comprehensively analyze the fundamental metabolites, mechanisms of action, and toxic effects of TCM. This comprehensive approach can provide valuable insights into the intricate relationship between the effect and toxicity of these TCM.

Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses.

Background: Resveratrol, a polyphenol found in various plants, is known for its diverse bioactivities and has been explored in relation to nonalcoholic fatty liver disease (NAFLD). However, no high-quality evidence exists regarding its efficacy. Objective: a meta-analysis was conducted to evaluate the potential efficacy of resveratrol in treating nonalcoholic fatty liver disease by analyzing both preclinical studies and clinical trials. Method: PubMed, Embase and Web of Science were searched for the included literature with the criteria for screening. Quantitative synthesis and meta-analyses were performed by STATA 16.0. Results: Twenty-seven studies were included, and the results indicated that resveratrol effectively improved liver function, reduced fatty liver indicators, and affected other indices in preclinical studies. The effective dosage ranged from 50 mg/kg-200 mg/kg, administered over a period of 4-8 weeks. While there were inconsistencies between clinical trials and preclinical research, both study types revealed that resveratrol significantly reduced tumor necrosis factor-α levels, further supporting its protective effect against nonalcoholic fatty liver disease. Additionally, resveratrol alleviated nonalcoholic fatty liver disease primarily via AMPK/Sirt1 and anti-inflammatory signaling pathways. Conclusion: Current meta-analysis could not consistently verify the efficacy of resveratrol in treating nonalcoholic fatty liver disease, but demonstrated the liver-protective effects on nonalcoholic fatty liver disease. The large-sample scale and single region RCTs were further needed to investigate the efficacy.

Staged or simultaneous operations for ventriculoperitoneal shunt and cranioplasty: Evidence from a meta-analysis.

OBJECTIVE: To date, there is no consensus on the surgery strategies of cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. This meta-analysis aimed to investigate the safety of staged and simultaneous operation in patients with comorbid cranial defects with hydrocephalus to inform future surgery protocols. METHODS: A meta-analysis of PubMed, Ovid, Web of Science, and Cochrane Library databases from the inception dates to February 8, 2023 adherent to PRISMA guidelines was conducted. The pooled analyses were conducted using RevMan 5.3 software. The outcomes included postoperative infection, reoperation, shunt obstruction, hematoma, and subdural effusion. RESULTS: Of the 956 studies initially retrieved, 10 articles encompassing 515 patients were included. Among the total patients, 193 (37.48%) and 322 (62.52%), respectively, underwent simultaneous and staged surgeries. The finding of pooled analysis indicated that staged surgery was associated with lower rate of subdural effusion (14% in the simultaneous groups vs. 5.4% in the staged groups; OR = 2.39, 95% CI: 1.04-5.49, p = 0.04). However, there were no significant differences in overall infection (OR = 1.92, 95% CI: 0.74-4.97, p = 0.18), central nervous system infection (OR = 1.50, 95% CI: 0.68-3.31, p = 0.31), cranioplasty infection (OR = 1.58, 95% CI: 0.50-5.00, p = 0.44), shunt infection (OR = 1.30, 95% CI: 0.38-4.52, p = 0.67), reoperation (OR = 1.51, 95% CI: 0.38-6.00, p = 0.55), shunt obstruction (OR = 0.73, 95% CI: 0.25-2.16, p = 0.57), epidural hematoma (OR = 2.20, 95% CI: 0.62-7.86, p = 0.22), subdural hematoma (OR = 1.20, 95% CI: 0.10-14.19, p = 0.88), and intracranial hematoma (OR = 1.31, 95% CI: 0.42-4.07, p = 0.64). Moreover, subgroup analysis failed to yield new insights. CONCLUSIONS: Staged surgery is associated with a lower rate of postoperative subdural effusion. However, from the evidence of sensitivity analysis, this result is not stable. Therefore, our conclusion should be viewed with caution, and neurosurgeons in practice should make individualized decisions based on each patient's condition and cerebrospinal fluid tap test.

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives.

Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.

Lung microbiome and cytokine profiles in different disease states of COPD: a cohort study.

Increasing evidence indicates that respiratory tract microecological disorders may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Understanding the composition of the respiratory microbiome in COPD and its relevance to respiratory immunity will help develop microbiome-based diagnostic and therapeutic approaches. One hundred longitudinal sputum samples from 35 subjects with acute exacerbation of COPD (AECOPD) were analysed for respiratory bacterial microbiome using 16S ribosomal RNA amplicon sequencing technology, and the sputum supernatant was analysed for 12 cytokines using a Luminex liquid suspension chip. Unsupervised hierarchical clustering was employed to evaluate the existence of distinct microbial clusters. In AECOPD, the respiratory microbial diversity decreased, and the community composition changed significantly. The abundances of Haemophilus, Moraxella, Klebsiella, and Pseudomonas increased significantly. Significant positive correlations between the abundance of Pseudomonas and TNF-α, abundance of Klebsiella and the percentage of eosinophils were observed. Furthermore, COPD can be divided into four clusters based on the respiratory microbiome. AECOPD-related cluster was characterized by the enrichment of Pseudomonas and Haemophilus and a high level of TNF-α. Lactobacillus and Veillonella are enriched in therapy-related phenotypes and may play potential probiotic roles. There are two inflammatory endotypes in the stable state: Gemella is associated with the Th2 inflammatory endotypes, whereas Prevotella is associated with the Th17 inflammatory endotypes. Nevertheless, no differences in clinical manifestations were found between these two endotypes. The sputum microbiome is associated with the disease status of COPD, allowing us to distinguish different inflammatory endotypes. Targeted anti-inflammatory and anti-infective therapies may improve the long-term prognosis of COPD.

14, 15-EET alleviates neurological impairment through maintaining mitochondrial dynamics equilibrium via AMPK/SIRT1/FoxO1 signal pathways in mice with cerebral ischemia reperfusion.

AIM: To explore whether 14, 15-EET regulates mitochondrial dynamics to exert neuroprotective effects after cerebral ischemia-reperfusion and its underlying mechanisms. METHODS: The mouse middle cerebral artery occlusion reperfusion model was used to observe brain infarct volume and neuronal apoptosis by TTC staining and Tunel assay, modified neurological severity score to detect neurological impairment, HE staining and Nissl staining to observe neuron damage, western blot and immunofluorescence methods to detect the expression of mitochondrial dynamics-related proteins, transmission electron microscopy, and Golgi-Cox staining to detect mitochondrial morphology and neuronal dendritic spines. RESULTS: 14, 15-EET reduced the neuronal apoptosis and cerebral infarction volume induced by middle cerebral artery occlusion reperfusion (MCAO/R), inhibited the degradation of dendritic spines, maintained the structural integrity of neurons, and alleviated neurological impairment. Cerebral ischemia-reperfusion induces mitochondrial dynamics disorders, upregulates the expression of the mitochondrial division protein Fis 1, and inhibits the expression of mitochondrial fusion proteins MFN1, MFN2, and OPA1, while 14, 15-EET treatment reverses this process. Mechanistic studies have shown that 14, 15-EET promotes the phosphorylation of AMPK, upregulates the expression of SIRT1 and phosphorylation of FoxO1, thereby inhibiting mitochondrial division and promoting mitochondrial fusion, preserving mitochondrial dynamics, maintaining neuronal morphological and structural integrity, and alleviating neurological impairment induced by middle cerebral artery occlusion reperfusion. Compound C treatment diminishes the neuroprotective effect of 14, 15-EET following MCAO/R in mice. CONCLUSION: This study elucidates the novel neuroprotective mechanism of 14, 15-EET, providing a novel approach for the development of drugs based on mitochondrial dynamics.

Preclinical and clinical evidence for the treatment of non-alcoholic fatty liver disease with soybean: A systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD), a prevalent public health issue, involves the accumulation of triglycerides in hepatocytes, which is generally considered to be an early lesion of liver fibrosis and cirrhosis. Thus, the development of treatments for NAFLD is urgently needed. This study explored the preclinical and clinical evidence of soybeans to alleviate NAFLD. Studies indexed in three relevant databases-Web of Science, PubMed, and Embase-between January 2002 and August 2022 were retrieved. A total of 13 preclinical studies and five RCTs that included 212 animals and 260 patients were included in the present analysis. The preclinical analysis showed that liver function indices (AST, SMD = -1.41, p < 0.0001 and ALT, SMD = -1.47, p < 0.0001) were significantly improved in the soybean group compared to the model group, and fatty liver indicators (TG, SMD = -0.78, p < 0.0001; TC, SMD = -1.38, p < 0.0001) and that oxidative stress indices (MDA, SMD = -1.09, p < 0.0001; SOD, SMD = 1.74, p = 0.022) were improved in the soybean group. However, the five RCTs were not entirely consistent with the preclinical results; however, the results confirmed the protective effect on the liver. The results of the clinical RCTs showed that soybean significantly affected liver function, fatty liver, and oxidative stress indicators (ALT, SMD = -0.42, p = 0.006; TG, SMD = -0.31, p = 0.039; MDA, SMD = -0.76, p = 0.007). The current meta-analysis combined preclinical and clinical studies and verified that soybean could protect the liver in NAFLD by regulating lipid metabolism and oxidative stress factors via the Akt/AMPK/PPARα signaling pathway. Soybean might be a promising therapeutic agent for treating non-alcoholic fatty liver disease. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#myprospero), identifier (CRD42022335822).

Diabetic nephropathy: Focusing on pathological signals, clinical treatment, and dietary regulation.

Diabetic nephropathy (DN) is one of the most severe complications of diabetes. However, due to its complex pathological mechanisms, no effective therapeutic methods (other than ACEIs and ARBs) have been applied, which have been used for many years in clinical practice. Recent studies have shown that emerging therapeutics, including novel target-based pharmacotherapy, cell therapies, and dietary regulation, are leading to new hopes for DN management. This review aims to shed new light on the treatment of DN by describing the important pathological mechanisms of DN and by analysing recent advances in clinical treatment, including drug therapy, cell therapy, and dietary regulation. In pathological mechanisms, RAAS activation, AGE accumulation, and EMT are involved in inflammation, cellular stress, apoptosis, pyroptosis, and autophagy. In pharmacotherapy, several new therapeutics, including SGLT2 inhibitors, GLP-1 agonists, and MRAs, are receiving public attention. In addition, stem cell therapies and dietary regulation are also being emphasized. Herein, we highlight the importance of combining therapy and dietary regulation in the treatment of DN and anticipate more basic research or clinical trials to verify novel strategies.

Using POI and time series Landsat data to identify and rebuilt surface mining, vegetation disturbance and land reclamation process based on Google Earth Engine.

The development of coal resources is necessary, but it has a huge negative impact on land, ecology, and the environment. With the increasing awareness of environmental protection and the requirements of related regulations, the design and practice of reclamation projects run through the mining life cycle and continue for a long time after the coal production. High-precision monitoring of mining disturbance and reclamation, quantifying the degree and time of vegetation disturbance and restoration, is of great significance to minimize the environmental effect of mining. Remote sensing, widely used as efficient monitoring tool, but there is not enough research on disturbance and reclamation monitoring taking into account large-scale areas and high temporal and spatial accuracy. Especially when mining sites remain unknown, how to distinguish the disturbance of coal mining and other human activities affecting the surface land cover has become a challenge. Therefore, this paper proposed a method to reconstruct the time series of mining disturbance and reclamation in a large area by using the POI (point of interest) and Landsat time series images using multiple buffer analysis methods. The process includes: (1) Retrieval of POI in the study area based on the public mining list using Python crawler, and buffering 100 km for preliminary extraction of potential mining areas; (2) Using spectral index mask and random forest algorithm to accurately extract the exposed coal on the Google Earth Engine (GEE) platform; (3) Buffering 10 km to identify the occurrence of disturbance and reclamation, using pixel-based temporal trajectory identification of LandTrendr algorithm under GEE. The method successful detect the change points of surface coal mining disturbance and reclamation in eastern Inner Mongolia of China. The results show that: (1) The method can effectively identify the extent of surface coal mining disturbance and reclamation, and the overall extraction accuracy is 81%. (2) Surface coal mining disturbance in eastern Inner Mongolia was concentrated in 2006-2011. By 2020, the total disturbed area is 627.8 km2, with an average annual disturbance of 18.5 km2, and the annual maximum disturbance to the ground reached 64.6 km2 in 2008. With the total reclaimed area being 236.3 km2, the reclamation rate is about 37.6%. This study provides a systematic solution and process for monitoring the disturbance and reclamation of surface coal mining in a large range with little known about the mines' location. It can effectively identify the mining disturbance and reclamation process which can also be extended to other areas, providing a quantitative assessment of mining disturbance and reclamation, which can support further ecological restoration decision-making.

Omadacycline for the treatment of severe pneumonia caused by Chlamydia psittaci complicated with acute respiratory distress syndrome during the COVID-19 pandemic.

Introduction: Chlamydia psittaci infection in humans is a rare cause that mainly present as community-acquired pneumonia. Severe Chlamydia psittaci pneumonia can lead to acute respiratory distress syndrome (ARDS), septic shock, or multiple organ dysfunction with a mortality rate of 15%-20% before accurate diagnosis and targeted treatment. Metagenomic next-generation sequencing (mNGS) has an advantage in achieving early diagnosis. In the study, omadacycline implementation was described to provide a better understanding of effectiveness in severe psittacosis pneumonia with ARDS. Methods: Sixteen patients with severe psittacosis pneumonia with ARDS were selected between September 2021 and October 2022. They were diagnosed using mNGS and treated with omadacycline. Retrospective analysis of clinical manifestations, laboratory data, disease progression, diagnostic tool, treatment, and prognosis was summarized. Results: Common symptoms included fever, dyspnea, and cough. All patients developed ARDS, accompanied by septic shock (43.7%) and pulmonary embolism (43.7%). Laboratory data showed normal leucocytes, increased creatine kinase isoenzyme, and decreased albumin with liver dysfunction in most patients. All patients had increased neutrophils, C-reactive protein, procalcitonin, and D-dimer with decreased lymphocytes. Airspace consolidation, ground glass opacity, and pleural effusion were found on chest CT. mNGS results were obtained in 24-48 h to identify the diagnosis of Chlamydia psittacosis. All patients received mechanical ventilation with omadacycline treatment. Fourteen patients experienced complete recovery, while the other two patients died from multidrug-resistant bacterial infection and renal failure. Conclusion: mNGS has a significant value in the diagnosis of Chlamydia psittaci infection. Timely treatment of omadacycline can improve prognosis and provide a promising new option for the treatment of severe Chlamydia psittaci pneumonia with ARDS.