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Oxidative stress is one of the important factors in the development of alcoholic liver disease. The production of reactive oxygen species and other free radicals is an important feature of alcohol metabolism in the liver and an important substance in liver injury. When large amounts of ROS are produced, the homeostasis of the liver REDOX system will be disrupted and liver injury will be caused. Oxidative stress can damage proteins, nucleic acids and lipids, liver dysfunction. In addition, damaging factors produced by oxidative damage to liver tissue can induce the occurrence of inflammation, thereby aggravating the development of ALD. This article reviews the oxidative damage of alcohol on liver proteins, nucleic acids, and lipids, and provides new insights and summaries of the oxidative stress process. We also discussed the relationship between oxidative stress and inflammation in alcoholic liver disease from different perspectives. Finally, the research status of antioxidant therapy in alcoholic liver disease was summarized, hoping to provide better help for learning and developing the understanding of alcoholic liver disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhengquan Su reports that funding was provided by Guangdong Pharmaceutical University. Zhengquan Su reports a relationship with Guangdong Pharmaceutical University that includes: If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Fufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway., Aim of the Study: To explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway., Materials and Methods: We induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting., Results: FTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner., Conclusion: FTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives., (© 2024 Wiley Periodicals LLC.)

Amelioration of hypercholesterolemia is essential for the treatment of atherosclerotic cardiovascular disease. Sodium sulphate is the effective component of mirabilite, which has been used in traditional Chinese medicine for the treatment of various diseases. In the present study, C57BL/6 mice were fed with a high-cholesterol diet (HCD) for 7 weeks and were treated with sodium sulphate in the last three of those weeks. Sodium sulphate significantly reduced the total cholesterol level and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in the serum of mice fed the HCD. In addition, cytochrome P450 7a1 and 39a1 were significantly upregulated in the livers of mice treated with sodium sulphate. Furthermore, tribbles pseudokinase 3 expression was significantly increased in the livers of mice fed the HCD, but was significantly reduced by sodium sulphate treatment. In terms of the insulin signaling pathway, the ratio of phosphorylated AKT to total AKT in the livers of mice fed the HCD was significantly lower compared with that of control mice fed a normal diet, but was significantly increased by sodium sulphate treatment. Sodium sulphate treatment also reduced the levels of fibroblast growth factor (FGF)15 in the ileum and inhibited the FGF15/FGF receptor 4-Klotho β/c-Jun N-terminal kinase/c-Jun signaling pathway in the livers of mice fed the HCD. In addition, sodium sulphate changed the composition of the gut microbiota of mice fed the HCD. In conclusion, sodium sulphate may mitigate hypercholesterolemia and hepatic insulin resistance in mice fed an HCD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yang et al.)

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 ​N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPC L84N or GPC K88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 ​N ​> ​L107F ​> ​K88E ​> ​H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD., Competing Interests: The authors declare no conflicts of interest.

The pathogenesis of neuropathic pain (NP) is complex, and there are various pathological processes. Previous studies have suggested that lncRNA PCAT19 is abnormally expressed in NP conduction and affects the occurrence and development of pain. The aim of this study is to analyze the role and mechanism of PCAT19 in NP induced by chronic compressive nerve injury (CCI) in mice. In this study, C57BL/6 mice were applied to establish the CCI model. sh-PCAT19 was intrathecally injected once a day for 5 consecutive days from the second day after surgery. We discovered that PCat19 level was gradually up-regulated with the passage of modeling time. Downregulation of Iba-1-positive expression, M1/M2 ratio of microglia, and pro-inflammatory factors in the spinal cords of CCI-mice after PCat19 knock-downed was observed. Mechanically, the expression of miR-378a-3p was negatively correlated with KDM3A and PCat19. Deletion of KDM3A prevented H3K9me2 demethylation of BDNF promoter and suppressed BDNF expression. Further, KDM3A promotes CCI-induced neuroinflammation and microglia activation by mediating Brain-derived neurotrophic factor (BDNF) demethylation. Together, the results suggest that PCat19 may be involved in the development of NP and that PCat19 shRNA injection can attenuate microglia-induced neuroinflammation by blocking KDM3A-mediated demethylation of BDNF and BDNF release., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO 2 ) nanospheres (NPs) (ICG@MnO 2 ), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO 2 @Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO 2 @Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO 2 catalyzes the conversion of H 2 O 2 to O 2 , thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O 2 to produce singlet oxygen ( 1 O 2 ) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H 2 O 2 reduces MnO 2 to Mn 2+ , which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO 2 @Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC., Competing Interests: The authors declare no competing interest., (© 2024 The Authors.)

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34 + hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

Background: Research on the Chinese herbal formula Fufang Zhenzhu Tiaozhi (FTZ) has demonstrated its effectiveness in treating hyperlipidemia and glycolipid metabolic disorders. Additionally, FTZ has shown inhibitory effects on oxidative stress, regulation of lipid metabolism, and reduction of inflammation in these conditions. However, the precise mechanisms through which FTZ modulates macrophage function in atherosclerosis remain incompletely understood. Therefore, this study aims to investigate whether FTZ can effectively stabilize rupture-prone plaques by suppressing macrophage pyroptosis and impeding the development of M1 macrophage polarization in ApoE -/- mice., Methods: To assess the impact of FTZ on macrophage function and atherosclerosis in ApoE -/- mice, we orally administered FTZ at a dosage of 1.2 g/kg body weight daily for 14 weeks. Levels of interleukin-18 and interleukin-1β were quantified using ELISA kits to gauge FTZ's influence on inflammation. Total cholesterol content was measured with a Cholesterol Assay Kit to evaluate FTZ's effect on lipid metabolism. Aortic tissues were stained with Oil Red O, and immunohistochemistry techniques were applied to assess atherosclerotic lesions and plaque stability. To evaluate the effects of FTZ on macrophage pyroptosis and oxidative damage, immunofluorescence staining was utilized. Additionally, we conducted an analysis of protein and mRNA expression levels of NLRP3 inflammasome-related genes and macrophage polarization-related genes using RT-PCR and western blotting techniques., Results: This study illustrates the potential therapeutic effectiveness of FTZ in mitigating the severity of atherosclerosis and improving serum lipid profiles by inhibiting inflammation. The observed enhancements in atherosclerosis severity and inflammation can be attributed to the suppression of NLRP3 inflammasome activity and M1 polarization by FTZ., Conclusion: The current findings indicate that FTZ provides protection against atherosclerosis, positioning it as a promising candidate for novel therapies targeting atherosclerosis and related cardiovascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The electrolytes with high lithium-ion transference number (t Li+ ) can reduce the formation of concentration polarization during charge/discharge process and improve the electrochemical performance of lithium-ion batteries (LIBs). Herein, we report triblock copolymer electrolytes (PBOEE) containing borate. The sp 2 hybridized boron atoms acting as Lewis acids can anchor the anions of lithium salts, enabling PBOEE to achieve high t Li+ of up to 0.53. Also, the borate groups can promote the formation of stable organic-rich solid electrolyte interphase (SEI) film, which enables the Li symmetric cell to cycle stably at 0.1 mA cm -2 /0.1 mAh cm -2 for more than 3100 h with a low overpotential of 0.08 V under 50 °C. The optimized PBOEE_24 has an ionic conductivity of 1.41 × 10 -4 S cm -1 and electrochemical stability window of 4.8 V vs. Li + /Li at 50 °C. Combining these advantages, the LiFePO 4 /PBOEE_24/Li cell exhibits an initial discharge specific capacity of 157.3 mA h g -1 at 0.5C with a capacity retention of 85 % after 600 cycles under 50 °C. At a higher current density of 1C, the discharge capacity maintains at 128.0 mA h g -1 after 400 cycles with a capacity retention of 84.88 %. These results suggest that block copolymer containing sp 2 hybridized boron atoms is a promising all-solid-state polymer electrolyte., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.

Photocatalytic selective oxidation of alcohols into aldehydes and H 2 is a green strategy for obtaining both value-added chemicals and clean energy. Herein, a dual-purpose ZnIn 2 S 4 @CdS photocatalyst was designed and constructed for efficient catalyzing benzyl alcohol (BA) into benzaldehyde (BAD) with coupled H 2 evolution. To address the deep-rooted problems of pure CdS, such as high recombination of photogenerated carriers and severe photo-corrosion, while also preserving its superiority in H 2 production, ZnIn 2 S 4 with a suitable band structure and adequate oxidizing capability was chosen to match CdS by constructing a coupled reaction. As designed, the photoexcited holes (electrons) in the CdS (ZnIn 2 S 4 ) were spatially separated and transferred to the ZnIn 2 S 4 (CdS) by electrostatic pull from the built-in electric field, leading to expected BAD production (12.1 mmol g -1 h -1 ) at the ZnIn 2 S 4 site and H 2 generation (12.2 mmol g -1  h -1 ) at the CdS site. This composite photocatalyst also exhibited high photostability due to the reasonable hole transfer from CdS to ZnIn 2 S 4 . The experimental results suggest that the photocatalytic transform of BA into BAD on ZnIn 2 S 4 @CdS is via a carbon-centered radical mechanism. This work may extend the design of advanced photocatalysts for more chemicals by replacing H 2 evolution with N 2 fixation or CO 2 reduction in the coupled reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC 50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The functional performance of immune cells relies on a complex transcriptional regulatory network. The three-dimensional structure of chromatin can affect chromatin status and gene expression patterns, and plays an important regulatory role in gene transcription. Currently available techniques for studying chromatin spatial structure include chromatin conformation capture techniques and their derivatives, chromatin accessibility sequencing techniques, and others. Additionally, the recently emerged deep learning technology can be utilized as a tool to enhance the analysis of data. In this review, we elucidate the definition and significance of the three-dimensional chromatin structure, summarize the technologies available for studying it, and describe the research progress on the chromatin spatial structure of dendritic cells, macrophages, T cells, B cells, and neutrophils., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Xu, Yan, Li, Jia, Sun, Sheng, Wang, Zhang, Guo, Xin, Li and Guo.)

Chitosan oligosaccharides are the degradation products of chitin obtained from the shell extracts of shrimps and crabs. Compared with chitosan, chitosan oligosaccharides have better solubility and a wider application range. In this study, high-molecular-weight chitosan oligosaccharides (COST, chitosan oligosaccharides, MW ≤ 1000) were isolated and purified by a GPC gel column, and the molecular weight range was further reduced to obtain high-purity and low-molecular-weight chitosan (COS46). Compared with COST, COS46 is better at inhibiting CCl 4 -induced cell death, improving cell morphology, reducing ALT content, and improving cell antioxidant capacity. The effects of COST and COS46 on CCl 4 -induced acute liver injury were further verified in mice. Both COS46 and COST improved the appearance of the liver induced by CCl 4 , decreased the levels of ALT and AST in serum, and decreased the oxidation/antioxidant index in the liver. From the liver pathological section, the effect of COS46 was better. In addition, some indicators of COS46 showed a dose-dependent effect. In conclusion, compared with COST, low-molecular-weight COS46 has better antioxidant capacity and a better therapeutic effect on CCl 4 -induced acute liver injury.

Cardiovascular disease (CVD) stands as the foremost cause of patient mortality, and the lack of early diagnosis and defined treatment targets significantly contributes to the suboptimal prevention and management of CVD. Myocardial fibrosis (MF) is not only a complex pathogenic process with no effective treatment currently available but also exerts detrimental effects on the progression of various cardiovascular diseases, thereby escalating their mortality rates. Exosomes are nanoscale biocommunication vehicles that facilitate intercellular communication by transporting bioactive substances, such as nucleic acids and proteins, from specific cell types. Numerous studies have firmly established that microRNAs (miRNAs), as non-coding RNAs, wield post-transcriptional regulatory mechanisms and exhibit close associations with various CVDs, including coronary heart disease (CHD), atrial fibrillation (AF), and heart failure (HF). MiRNAs hold significant promise in the diagnosis and treatment of cardiovascular diseases. In this review, we provide a concise introduction to the biological attributes of exosomes and exosomal miRNAs. We also explore the roles and mechanisms of distinct cell-derived exosomal miRNAs in the context of myocardial fibrosis. These findings underscore the pivotal role of exosomes in the diagnosis and treatment of cardiac fibrosis and emphasize their potential as biotherapies and drug delivery vectors for cardiac fibrosis treatment.

Ethnopharmacological Relevance: In the progression of chronic liver diseases, liver fibrosis is a reversible pathophysiologic event for liver diseases prognosis and risk of cirrhosis. Liver injury factors of different etiologies mediate this process. There is still a lack of effective medications for treating liver fibrosis. Additionally, the ameliorative effects of traditional herbs on liver fibrosis have been commonly reported. Tianhuang formula (THF) is a drug combination consisting of 2 traditional Chinese herbs, which has been showing significant improvement in metabolic liver diseases. However, the hepatoprotective effect and mechanism of THF in ameliorating liver fibrosis are still unclear., Aim of the Study: This study aimed to investigate the effects of THF on carbon tetrachloride (CCl 4 )-induced and methionine-choline-deficient (MCD) diet-induced liver fibrosis model and to reveal the potential mechanisms. It can provide experimental evidence for THF as a therapeutic candidate for liver fibrosis., Materials and Methods: In this study, CCl 4 -induced mice were treated with THF (80 mg/kg, 160 mg/kg) or Fuzheng Huayu (FZHY) capsules (4.8 g/kg) for 6 weeks. MCD-induced mice received the same doses of THF or FZHY for 4 weeks. FZHY is used as a comparative study in these two models. Following that, using kit reagents detected changes in relevant serum and liver biochemical indicators. Histological changes in mouse liver were measured by staining of H&E and Sirius Red. The markers expression of liver fibrosis and inflammation were detected using qRT-PCR, western blotting and immunohistochemical staining analysis. The potential regulatory mechanism of THF to ameliorate liver fibrosis was performed by RNA-sequencing analysis. Finally, the analysis results were verified by immunofluorescence co-staining, qRT-PCR and western blotting., Results: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic triglyceride (TG) levels in CCl 4 and MCD-induced liver fibrosis mice were significantly improved after THF treatment. Meanwhile, the expression of fibrosis and inflammation markers were significantly suppressed. Furthermore, THF downregulated the expression of the macrophage marker CD68. According to RNA-sequencing analysis, we found the CCL2-CCR2 axis and MAPK/NF-κB as the potential signaling pathway for THF against liver fibrosis., Conclusion: This study revealed that THF ameliorated liver injury, inflammation and fibrotic process by inhibiting CCL2-CCR2 axis and its downstream MAPK/NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates ( P  < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

Zinc oxide nanoparticles (ZnO NPs) have emerged as a novel solution to combat Zn deficiency in agriculture. However, challenges persist regarding their Zn utilization efficiency and environmental impact. Fulvic acid (FA), as a relatively mature modified material, is a promising candidate to enhance the environmental stability of ZnO NPs. This study investigates modifying ZnO NPs with FA to improve their stability and increase Zn content in mung bean fruit and explores their effect on plants and the soil ecosystem. We combined FA and ZnO NPs (FZ-50) at mass ratios of 1: 5, 1: 2, and 4: 5, denoted as 20 % FZ, 50 % FZ, and 80 % FZ, respectively. Initial germination tests revealed that the 50 % FZ treatment improved sprout growth and Zn content and minimized agglomeration the most. A subsequent pot experiment compared FZ-50 with ZnO, ZnO NPs, and F + Z (1: 1 FA: ZnO NPs). Notably, the FZ-50 treatment (50 % FZ applied to the soil) demonstrated superior results, exhibiting a 30.25 % increase in yield, 121 % improvement in root nodule quality, and 56.38 % increase in Zn content, with no significant changes in enzyme activities (catalase and peroxidase). Furthermore, FZ-50 increased soil available Zn content and promoted soil microorganism diversity, outperforming ZnO and ZnO NPs. This study underscores the potential of FA as a relatively mature material for modifying ZnO NPs to increase grain Zn content, presenting a novel approach to addressing Zn deficiency in agriculture., Competing Interests: Declaration of competing interest The article has no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very important role in the synthesis of human and animal cartilage. GLC is commonly used in the treatment of mild to moderate osteoarthritis and has good anti-inflammatory and antioxidant properties. In this study, alcoholic injury models were constructed in mice and human normal hepatocyte L02 cells to explore the protective effect and mechanism of GLC on ALD. Mice were given GLC by gavage for 30 days. Liver injury models of both mice and L02 cells were produced by ethanol. Detecting the levels of liver injury biomarkers, lipid metabolism, oxidative stress biomarkers, and inflammatory factors through different reagent kits. Exploring oxidative and inflammatory pathways in mouse liver tissue through Western blot and RT-PCR. The results showed that GLC can significantly inhibit the abnormal increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), and can significantly improve the level of high-density lipoprotein cholesterol (HDL-C). In addition, GLC intervention significantly improved alcohol induced hepatic oxidative stress by reducing the levels of malondialdehyde (MDA) and, increasing the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the liver. Further mechanisms suggest that GLC can inhibit the expression of ethanol metabolism enzyme cytochrome P4502E1 (CYP2E1), activate the antioxidant pathway Keap1/Nrf2/HO-1, down-regulate the phosphorylation of MAPK and NF-κB signaling pathways, and thus reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Therefore, GLC may be a significant candidate functional food for attenuating alcohol induced acute liver injury., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Weiwen Lai reports financial support was provided by 10.13039/501100008366Guangdong Pharmaceutical University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

TGF-β is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-β pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-β inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-β inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-β blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-β pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity., (© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Lanostane-type triterpenoids are the main characteristic constituents in Ganoderma mushrooms. Phytochemical analysis on the ethanol extract of the fruiting bodies of Ganoderma amboinense led to isolation and identification of twelve previously undescribed lanostane triterpenoids (1-12). Their chemical structures were determined by HR-ESI-MS, IR, and NMR spectroscopic analysis, NMR calculation, as well as X-ray crystallography. All isolates were evaluated for the α-glucosidase inhibitory and anti-inflammatory activities. Compounds 1, 5, 6, and 11 showed significant α-glucosidase inhibitory activity with IC 50 values ranging from 33.5 μM to 96.0 μM. Moreover, compound 12 showed anti-inflammatory activity with IC 50 value of 21.7 ± 2.1 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Japanese encephalitis virus (JEV) belongs to the Flaviviridae family and is a representative mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. Despite the availability of vaccines, JEV remains a major public health threat with the potential to spread globally. According to the World Health Organization (WHO), there are an estimated 69,000 cases of JE each year, and this figure is probably an underestimate. The majority of JE victims are children in endemic areas, and almost half of the surviving patients have motor or cognitive sequelae. Thus, the absence of a clinically approved drug for the treatment of JE defines an urgent medical need. Recently, several promising and potential drug candidates were reported through drug repurposing studies, high-throughput drug library screening, and de novo design. This review focuses on the historical aspects of JEV, the biology of JEV replication, targets for therapeutic strategies, a target product profile, and drug development initiatives.

Background: The role of mitochondrial dynamics, encompassing fission, fusion, and mitophagy, in cancer progression has been extensively studied. However, the specific impact of mitochondrial dynamics on hepatocellular carcinoma (HCC) is still under investigation., Methods: In this study, mitochondrial dynamic genes were obtained from the MitoCarta 3.0 database, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Based on the expression of these dynamic genes and differentially expressed genes (DEGs), patients were stratified into two clusters. Subsequently, a prognostic model was constructed using univariate COX regression and the least absolute shrinkage and selection operator (LASSO) regression, and the prognostic signature was evaluated. We analyzed the interaction between these model genes and dynamic genes to identify hub genes and reveal mitochondrial status. Furthermore, we assessed immune infiltration, tumor mutational burden (TMB), tumor stemness indices (TSI), and the response to immune checkpoint block (ICB) therapy using the TIDE algorithm and risk scores. Additionally, transmission electron microscopy (TEM), hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), western blotting (WB), and immunofluorescence (IF) were conducted to afford detailed visualization of the morphology of the mitochondria and the expression patterns of fission-associated proteins., Results: Patients in Cluster 2 exhibited heightened mitochondrial fission and had a worse prognosis. The up-regulated dynamic genes in Cluster 2 were identified as fission genes. GO/KEGG analyses reconfirmed the connection of Cluster 2 to augmented mitochondrial fission activities. Subsequently, a ten-gene prognostic signature based on the differentially expressed genes between the two clusters was generated, with all ten genes being up-regulated in the high-risk group. Moreover, the potential links between these ten signature genes and mitochondrial dynamics were explored, suggesting their involvement in mediating mitochondrial fission through interaction with MTFR2. Further investigation revealed that the high-risk group had an unfavorable prognosis, with a higher mutation frequency of TP53, increased immune checkpoint expression, a higher TIS score, and a lower TIDE score. The mitochondrial imbalance characterized by increased fission and upregulated MTFR2 and DNM1L expression was substantiated in both HCC specimens and cell lines., Conclusions: In conclusion, we developed a novel MTFR2-related prognostic signature comprising ten mitochondrial dynamics genes. These genes play crucial roles in mitochondrial fission and have the potential to serve as important predictors and therapeutic targets for HCC., (© 2024. The Author(s).)

Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development. Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a "camouflage cloak" to mimic the "don't eat me" mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading. Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively. Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Previous studies showed that physical activity (PA) is concerned with hypertension (HTN). However, the mediation and interaction role of the obesity index: body mass index (BMI), waist-hip ratio (WHR), body fat rate (BFR) and visceral fat index (VFI) between PA and HTN has never been studied. Therefore, the purpose of this study was to assess the mediation and interaction of the obesity index between moderate-vigorous recreational physical activity (MVRPA) and HTN. We conducted a cross-sectional study of 4710 individuals aged 41 or older in Torch Development Zone, Zhongshan City. The mediation and interaction of the obesity index were evaluated by a four-way decomposition. 48.07% of participants had HTN among these groups. In the adjusted linear regression model, MVRPA was significantly correlated with WHR (β±SE = -0.005±0.002; P<0.05). Compared to sufficient MVRPA (odds ratio (OR) = 1.35), 95% (confidence interval (CI) = 1.17-1.56), insufficient MVRPA increased the risk of developing HTN. Furthermore, there were associations between BMI, WHR, BFR, VFI and HTN where the adjusted ORs and 95% CIs were 1.11 (1.09-1.13), 6.23 (2.61-14.90), 1.04 (1.03-1.06), 1.07 (1.06-1.09), respectively. The mediation analyses suggested that the impact of MVRPA on HTN risk may partly be explained by changes in obesity index, with a pure indirect mediation of WHR between MVRPA and HTN (P<0.05). Therefore, weight control, especially reducing abdominal obesity and maintaining adequate MVRPA, may lead to more proper control of HTN., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ethnopharmacological Relevance: Fufang Zhenzhu TiaoZhi (FTZ), a Chinese medicinal decoction, has continuously been used to treat metabolic syndrome. Atherosclerosis is the main pathological basis of cardiovascular disease. The N6 methyladenosine (m 6 A) modification is a highly dynamic and reversible process involving a variety of important biological processes., Aim of the Study: Here, we investigated the therapeutic effects and mechanism of FTZ in diabetes-accelerated atherosclerosis., Materials and Methods: Doppler ultrasonography was used to examine the carotid intima-media thickness and plaque area in diabetic atherosclerosis patients. HFD mice were injected with streptozotocin to induce diabetes. HE and Oil red O staining were used to assess the effect of FTZ on lipid deposition. HUVECs were induced with HG/ox-LDL as a model of diabetic atherosclerosis. Furthermore, application of m 6 A methylation level kit, qRT-PCR, Western blot, tunel staining, reactive oxygen species staining and mPTP staining were performed to analyze the detailed mechanism., Results: Clinical trials of FTZ have shown obvious effect of lowering blood glucose and blood lipids. These effects were reversed after FTZ intervention. Compared with the control, lipid deposition decreased significantly after FTZ administration. FTZ reduced endothelial cell apoptosis. At the same time, we found that FTZ reversed the increase of methylation reader YTHDF2 caused by ox-LDL treatment. Subsequently, we discovered that YTHDF2 degraded SIRT3 mRNA, leading to endothelial cell apoptosis and oxidative stress., Conclusion: FTZ attenuated diabetes-accelerated atherosclerosis by decreasing blood glucose and serum lipids levels, and increased endothelial cell antioxidant capacity, inhibited endothelial cell apoptosis via inhibiting YTHDF2-mediated m6A modification of SIRT3 mRNA, which reduced mRNA degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Eight previously undescribed indole-diterpenoids named penerpenes O-V (1-8), together with seven known analogues (9-14), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Their structures including the absolute configurations of these compounds were assigned on the basis of spectroscopic data and ECD analysis along with quantum ECD and NMR calculations. Compounds 4 and 5 bear rare indolin-2-one units in their structures and 6 bears a reconstructed novel skeleton in which the indole ring and the terpenoid substructure are cleaved before they are reconnected through the nitrogen atom. Compounds 1, 2, 7, and 10 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activities comparable to that of the positive control NaVO 3 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Previous studies have found that chitosan oligosaccharide (COST) can alleviate the clinical symptoms in non-alcoholic fatty liver disease (NAFLD) patients. We intend to intervene with different concentrations of COST in mice with NAFLD induced by a high fat diet. The basic effect of COST on NAFLD model mice was observed using physiological and biochemical indexes. 16S rRNA sequencing technology was used to analyze the gut microbiota and further analyze the content of short-chain fatty acids (SCFAs). Western blot and RT-PCR were used to detect the effects of COST on the PI3K/AKT/mTOR signaling pathway in the livers of NAFLD mice. It was found that the COST-high-dose group could reduce the weight of NAFLD mice, improve dyslipidemia, and alleviate liver lesions, and COST has a therapeutic effect on NAFLD mice. 16S rRNA sequencing analysis showed that COST could increase the diversity of the gut microbiota in NAFLD mice. The downregulation of SCFAs in NAFLD mice was reversed. WB and RT-PCR results showed that the PI3K/AKT/mTOR signaling pathway was involved in the development of NAFLD mice. COST improved liver lipid metabolism in NAFLD mice by inhibiting liver DNL. COST could increase the expression of thermogenic protein and UCP1 and PGC-1α genes; the PI3K/AKT/mTOR signaling pathway is inhibited at the protein and gene levels. This study revealed that COST regulates the expression of related inflammatory factors caused by lipid toxicity through the gut microbiota and SCFAs, and improves the liver lipid metabolism of HFD-induced NAFLD mice, laying a foundation for the development of effective and low toxicity drugs for the treatment of NAFLD.

Aim: To investigate the changes in corneal biomechanics and posterior corneal surface elevation after femtosecond laser-assisted in situ keratomileusis (FS-LASIK)., Methods: Totally 197 eyes of 100 patients who underwent the FS-LASIK from April 2022 to November 2022 were included. They were divided into three groups according to the ratio of residual corneal stroma thickness/corneal thickness (RCST/CT): Group I (50%≤RCST/CT<55%, 63 eyes of 32 patients), Group II (55%≤RCST/CT<60%, 67 eyes of 34 patients), and Group III (RCST/CT≥60%, 67 eyes of 34 patients). The intraocular pressure (IOP), corneal compensated IOP (IOPcc), corneal hysteresis (CH) and corneal resistance factor (CRF) were measured immediately, 1, and 3mo postoperatively by ocular response analyzer (ORA) and the posterior elevation difference (PED) was measured by Pentacam., Results: After operation, IOP, CH, CRF, and PED were statistically different among the three groups ( F =12.99, 31.148, 23.998, all P <0.0001). There was no statistically significant difference in IOPcc among the three groups ( F =0.603, P >0.05). The IOP, IOPcc, CH, and CRF were statistical changed after surgery ( F =699.635, 104.125, 308.474, 640.145, all P <0.0001). The PED of Group I was significantly higher than that of Group II ( P <0.05), and Group II was significantly higher than that of Group III ( P <0.05). The PED value of 3mo after surgery decreased in each group compared with 1mo after surgery, but there was no statistical difference (Group I: t =0.82, P =0.41; Group II: t =0.17, P =0.87; Group III: t =1.35, P =0.18). The correlation analysis of corneal biomechanical parameter changes with PED at 1mo and 3mo after surgery showed that ΔIOP, ΔIOPcc, ΔCH, and ΔCRF were not correlated with PED value in three groups ( P >0.05)., Conclusion: The smaller the RCST/CT, the greater effect on corneal biomechanics and posterior surface elevation. There is no correlation between changes in corneal biomechanics and posterior corneal surface elevation in the range of RCST/CT≥50%., (International Journal of Ophthalmology Press.)

Fufang Zhenzhu Tiaozhi (FTZ) capsules have been prescribed for treating glucose and lipid metabolism disorders such as type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unknown. In this study, network pharmacology and experimental verification were combined to investigate the mechanisms of FTZ in treating T2DM. A total of 176 active ingredients and 1169 corresponding targets were screened using biological databases. 598 potential targets of T2DM were retrieved from GeneCards, PharmGKB, OMIM, Drugbank, and TTD. The Venn diagram was employed to identify the 194 intersection targets, which were employed to construct the "Herb-Compound-Target" interacting networks. These common targets were also used to prepare a protein-protein interaction (PPI) network to uncover potential targets. The four core targets were docked to their corresponding targets for binding analysis. Additionally, the top-ranked poses of ingredients and the positive compounds from each protein were evaluated for stability using molecular dynamics. Our results suggest that core active ingredients such as kaempferol, luteolin, and baicalein have high binding affinity and stability with AKT1, PTGS2 (also known as COX-2), DPP4, and PAPRG. GO and KEGG analyses indicated that the treatment T2DM by FTZ might be related to different pathway like AMPK and EGFR pathways. The experimental validation results proved that kaempferol, luteolin, and baicalein could significantly inhibit the activity of DPP4 and COX-2, kaempferol and luteolin were also able to activate AKT and AMPK signaling pathway. This study further validated previous findings and enhanced our understanding of the potential effects of FTZ on T2DM.Communicated by Ramaswamy H. Sarma.

Objective: To reveal the core mechanism of berberine (BBR) in the treatment of diabetic retinopathy (DR), by using Four-dimensional independent data acquisition (4D-DIA) proteomics combined bioinformatics analysis with experimental validation., Methods: DR injury model was established by injecting streptozotocin intraperitoneally. At 8 weeks after BBR administration, optical coherence tomography (OTC) photos and Hematoxylin-eosin staining from retina in each group were performed, then the retina was collected for 4D-DIA quantitative proteomics detection. Moreover, difference protein analysis, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI) network, as well as molecular docking was performed, respectively. In the part of experiment, Western blot (WB) and immunofluorescent staining was used to confirm the change and distribution of carbonic anhydrase 1 (CA1), one of the most important molecules from quantitative PCR detection. Lastly, RNA knockdown was used to determine the crucial role of CA1 in retinal pigment epithelial cells (RPEs) administrated with berberine., Results: OCT detection showed that the outer nucleus, inner layer and outer accessory layer of RPEs were thinned in DR group, compared with in sham one, while they were thickened after berberine administration, when compared with in DR group. 10 proteins were screened out by using proteomic analysis and Venny cross plot, in which, denn domain containing 1A (DENND1A) and UTP6 small subunit processome component (UTP6) was down-regulated, while ATPase copper transporting alpha (ATP7A), periplakin (PPL), osteoglycin (OGN), nse1 Homolog (NSMCE1), membrane metalloendopeptidase (MME), lim domain only 4 (LMO4), CA1 and fibronectin 1 (FN1) was up-regulated in DR group, and the BBR treatment can effectively reverse their expressions. PPI results showed that 10 proteins shared interactions with each other, but only ATP7A, FN1 and OGN exhibited directly associated with each other. Moreover, we enlarged the linked relation up to 15 genes in network, based on 10 proteins found from proteomics detection, so as to perform deep GO and KEGG analysis. As a result, the most important biological process is involving rRNA processing; the most important cell component is small subunit processor; the most important molecular function is Phospholipid binding; the KEGG pathway was Ribosome biogenesis in eukaryotes. Moreover, molecular docking showed that LMO4, ATP7A, PPL, NSMCE1, MME, CA1 could form a stable molecular binding pattern with BBR. Of these, the mRNA expression of CA1, PPL and ATP7A and the protein level of CA1 was increased in DR, and decreased in BBR group. Lastly, CA1 RNA knockdown confirmed the crucial role of CA1 in RPE administered with BBR., Conclusion: The present findings confirmed the role of BBR in DR treatment and explained associated molecular network mechanism, in which, CA1 could be considered as a crucial candidate in the protection of RPEs with berberine treatment., Competing Interests: Declaration of competing interest There is no conflict interest in this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Understanding the spatial and temporal variations of CO 2 column concentration (CO 2 -CCs) is crucial for tackling climate change and promoting sustainable human development. This study provides an in-depth analysis of CO 2 dynamics in the Yellow River Basin, an area significantly affected by both natural and anthropogenic factors. Using data from the Orbiting Carbon Observatory 2 (OCO-2) and the Fourier transformation spectrometer (FTS) of the GOSAT satellite remote sensing sensors, supplemented with ground station data from the Waliguan station, we scrutinized the CO 2 levels in the region from 2013 to 2022. The regional CO 2 -CC displayed a 12-month cyclical variation and a continuous upward trend, escalating by approximately 4.26% over the 10-year period. Spatiotemporal differences were evident in the monthly variation of CO 2 -CC, with peak and minimum values occurring in May and August respectively. Geographically, the highest CO 2 -CC was found in the central part of the basin, while the lowest was in the northern part of Inner Mongolia. This study underscores the increased significance of the region's CO 2 -CC, which showed an increase from 17.0 ppm at the start of the period to 21.0 ppm by the end, representing an overall growth of between 4.35 and 5.25%. The findings highlight the urgency of targeted measures to mitigate CO 2 emissions and adapt to their consequences in the Yellow River Basin, contributing to the global efforts against climate change and towards sustainable development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC 50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 μM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC 50 values of 30.2 ± 0.13 μM and 120.6 ± 0.14 μM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Disorders in glucose and lipid metabolism have been shown to exert an influence on bone metabolism. The TyG index, which combines measures of glucose and triglycerides, provides insights into the overall metabolic status. However, the investigation of concurrent disturbances in glucose and lipid metabolism and their specific implications for bone metabolism remains limited in the existing research literature. This study aimed to explore the correlation between the TyG index and bone mineral density (BMD) in US adults., Methods: In the National Health and Nutrition Examination Survey (NHANES), subjects were classified based on the TyG index into four groups (< 7.97, 7.97-8.39, 8.39-8.85, > 8.86). Linear regression analysis was conducted to determine the β value and 95% confidence interval (CI). Four multivariable models were constructed. Restricted cubic spline analyses and piecewise linear regression were employed to identify the association between the BMD and TyG index. An analysis of subgroups was also conducted in this study., Results: Significant variations in related characteristics were found among the US adult population, who were distributed into four groups based on the quartiles of the TyG index. A negative correlation between the TyG index and lumbar spine BMD was observed. In the multi-adjusted models, compared to Q1 of the TyG index, the β for Q4 of the TyG index for lumbar spine BMD was [β = - 0.008, 95% CI (- 0.017, 0)] in US adults. The association between the TyG index and lumbar spine BMD was found to be nonlinear (all nonlinear p < 0.001), with a threshold value based on restricted cubic spline analyses. Above the threshold point, the β for lumbar spine BMD was - 0.042 (95% CI, - 0.059, - 0.024). Below the threshold points, no significant difference was observed (p > 0.05). No significant interactions were observed among subgroups based on age, gender, presence of diabetes, BMI, and use of antidiabetic and antihyperlipidemic agents. Similar patterns of association were observed in total and subtotal bone density., Conclusions: This study identified a nonlinear association between the TyG index and BMD in the US population. Furthermore, an increased level of the TyG index may indicate a higher risk of osteoporosis among US adults. These findings highlight the importance of considering glucose and lipid metabolism disturbances in understanding bone health and the potential for developing preventive strategies for osteoporosis., (© 2023. The Author(s).)

Ethnopharmacological Relevance: Fufang-Zhenzhu-Tiaozhi capsule (FTZ), a Traditional Chinese Medicine (TCM) patent prescription commonly used in clinical practice, has a significant curative effect on hyperglycemia and hyperlipidemia. Previous studies have shown that FTZ can treat diabetes, but the effect of FTZ on β-cell regeneration needs to be further explored in T1DM mice., Aim of the Study: The aim is to investigate the role of FTZ in promoting β-cell regeneration in T1DM mice, and to further explore its mechanism., Materials and Methods: C57BL/6 mice were used as control. NOD/LtJ mice were divided into the Model group and FTZ group. Oral glucose tolerance, fasting blood glucose, and fasting insulin level were measured. Immunofluorescence staining was used to detect the level of β-cell regeneration and the composition of α-cells and β-cells in islets. Hematoxylin and eosin staining was used to detect the infiltration degree of inflammatory cells. The apoptosis of islet cells was detected by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Western blotting was used to detect the expression levels of Pancreas/duodenum homeobox protein 1 (PDX-1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA), and Neurogenin-3 (NGN3)., Results: FTZ could increase insulin levels and reduce the glucose level of T1DM mice and promote β-cell regeneration. FTZ also inhibited the invasion of inflammatory cells and the islet cell apoptosis, and maintained the normal composition of islet cells, thus preserving the quantity and quality of β-cells. Furthermore, FTZ promoting β-cell regeneration was accompanied by increasing the expression of PDX-1, MAFA, and NGN3., Conclusion: FTZ can restore the insulin-secreting function of the impaired pancreatic islet, improve blood glucose level, possibly via the enhancing β cell regeneration via upregulation of PDX-1, MAFA, and NGN3 in T1DM mice, and may be a potential therapeutic drug for T1DM., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is a liver disease syndrome. The prevalence of NAFLD has continued to increase globally, and NAFLD has become a worldwide public health problem. Glucosamine (GLC) is an amino monosaccharide derivative of glucose. GLC has been proven to not only be effective in anti-inflammation applications, but also to modulate the gut microbiota effectively. Therefore, in this study, the therapeutic effect of GLC in the NAFLD context and the mechanisms underlying these effects were explored. Specifically, an NAFLD model was established by feeding mice a high-fat and high-sugar diet (HFHSD), and the HFHSD-fed NAFLD mice were treated with GLC. First, we investigated the effect of treating NAFLD mice with GLC by analyzing serum- and liver-related indicator levels. We found that GLC attenuated insulin resistance and inflammation, increased antioxidant function, and attenuated serum and liver lipid metabolism in the mice. Then, we investigated the mechanism underlying liver lipid metabolism, inflammation, and intestinal barrier function in these mice. We found that GLC can improve liver lipid metabolism and relieve insulin resistance and oxidative stress levels. In addition, GLC treatment increased intestinal barrier function, reduced LPS translocation, and reduced liver inflammation by inhibiting the activation of the LPS/TLR4/NF-κB pathway, thereby effectively ameliorating liver lesions in NAFLD mice.

We aim to explore the pharmacological efficacy and molecular network mechanism of Shexiang Huayu Xingnao granules (SX granules) in the treatment of intracerebral hemorrhage (ICH) based on experiments and network pharmacology. After the ICH model establishment, the behavioral functions of rats were assessed by the modified neurological severity score (mNSS), the wire suspension test, and the rotarod test. Brain histomorphological changes were observed using 2,3,5-triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), Nissl, and TdT-mediated dUTP nick end labeling (TUNEL) combined with neuronal nuclear (NEUN) immunofluorescence staining. The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug-disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. In conclusion, SX granules improved behavioral dysfunction, abnormal alterations in brain tissue, and cell morphology in ICH rats, and potential molecular mechanism was linked with the expression of multiple genes., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)

Background: The Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora., Purpose: This study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis., Study Design and Methods: The DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300 mg/kg daily. Renal histological changes were measured by H&E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles., Results: Treatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage., Conclusion: These results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Silica nanoparticles (SiNPs) are being explored as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics. To translate laboratory innovation into clinical application, their potential toxicity has been of great concern. This review attempts to comprehensively summarize the existing literature on the toxicity assessment of SiNPs. The current data suggest that the composition of SiNPs, their physicochemical properties, their administration route, their frequency and duration of administration, and the sex of animal models are related to their tissue and blood toxicity, immunotoxicity, and genotoxicity. However, the correlation between in vitro and in vivo toxicity has not been well established, mainly because both the in vitro and the in vivo-dosed quantities are unrealistic. This article also discusses important factors to consider in the toxicology of SiNPs and current approaches to reducing their toxicity. The aim is to give readers a better understanding of the toxicology of silica nanoparticles and to help identify key gaps in knowledge and techniques., (© 2023. Controlled Release Society.)

Aim: To evaluate the effectiveness, safety, predictability, precision and changes of higher-order aberrations (HOAs) on corneal front surface of selective corneal wavefront aberration-guided femtosecond laser-assisted in situ keratomileusis (CW-FS-LASIK) in patients with high myopia 1-year postoperatively., Methods: Totally 74 eyes of 37 patients with high myopia or myopic astigmatism in both the eyes who underwent the CW-FS-LASIK procedure in Xi'an Gaoxin Hospital from January 2021 to June 2021 were included. The changes of uncorrected distance visual acuity (UDVA), best corrected visual acuity (BCVA), spherical equivalent refraction (SER), astigmatism, HOAs and Strehl ratio (SR) on the anterior surface of the cornea after 1y of the surgery were analyzed., Results: At postoperative 1y, the UDVA (logMAR) of 74 eyes (100%) reached 0 or better, including 0 in 8 eyes (10.81%), -0.1 in 45 eyes (60.81%), and -0.2 in 21 eyes (28.38%). The effectiveness index was 1.29±0.134. There was no decrease in postoperative BCVA compared with preoperative BCVA in all patients. Postoperative BCVA was the same in 44 eyes (59.46%) as preoperative BCVA, increased by 1 line in 23 eyes (31.08%) and increased by 2 lines in 7 eyes (9.46%) compared with preoperative BCVA. The safety index was 1.11±0.159. The estimated corrected SER before surgery was (-7.76±1.21) D, and the actual corrected SER was (-7.83±1.25) D ( Y =0.9811X+0.2156, R 2 =0.9084). There was a high correlation between the estimated corrected SER and the actual corrected SER. The postoperative SER in 74 eyes (100%) was within ±0.75 D. The postoperative astigmatism of all was within -0.75 D to 0. Root mean square (RMS) HOAs of spherical aberration and SR within 5 mm of the corneal front surface were all increased compared with those before operation ( P <0.01). The total coma, horizontal coma and vertical coma were all decreased compared with those before operation ( P <0.01). There was no statistically significant difference in horizontal trefoil and vertical trefoil compared with preoperative ones ( P >0.05)., Conclusion: Selective CW-FS-LASIK for correction of high myopia is effective, safe, predictive, and accurate. For patients with preoperative RMS HOAs over 0.25 defocus equivalent, postoperative coma aberration can be significantly reduced, and SR value can be increased, thus corneal imaging quality can be improved., (International Journal of Ophthalmology Press.)

Introduction: Polysaccharides, key components present in Grifola frondosa , can be divided into those derived from fruiting bodies, mycelium, and fermentation broth based on their source. The structure of G. frondosa fruiting body-derived polysaccharides has been fully characterized. However, the structure of G. frondosa mycelium-derived polysaccharides remains to be elucidated. Methods: In this study, we obtained mycelia from G. frondosa by liquid fermentation and extracted them with water and alkaline solution. Then, the mycelia were isolated and purified to obtain homogeneity and systematically characterized by methylation and FT infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. Results and discussion: Structural analysis showed that two neutral fractions (WGFP-N-a and AGFP-N-a 1 ) have a common backbone composed of α-1,6-D-Me-Gal p and α-1,6-D-Gal p that were substituted at O-2 by 1,2-Man p , α-1,3-L-Fuc p , and α-T-D-Man p and thus are identified as fucomannogalactans. WGFP-A-a, AGFP-A-b, and AGFP-A-c are β-1,6-glucans with different molecular weights and are branched with β-1,3-D-Glc p and T-D-Glc p at the O-3 of Glc. Our results provide important structural information about G. frondosa mycelium-derived polysaccharides and provide the basis for their further development and application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Geng, Wang, Guo, Han, Qu, Zhou, Tai, Sun and Cheng.)

Herein, an integrated structure of single Fe atom doped core-shell carbon nanoboxes wrapped by self-growing carbon nanotubes (CNTs) is designed. Within the nanoboxes, the single Fe atom doped hollow cores are bonded to the shells via the carbon needles, which act as the highways for the electron transport between cores and shells. Moreover, the single Fe atom doped nanobox shells is further wrapped and connected by self-growing carbon nanotubes. Simultaneously, the needles and carbon nanotubes act as the highways for electron transport, which can improve the overall electron conductivity and electron density within the nanoboxes. Finite element analysis verifies the unique structure including both internal and external connections realize the integration of active sites in nano scale, and results in significant increase in electron transfer and the catalytic performance of Fe-N 4 sites in both Li 2 S n lithiation and Li 2 S delithiation. The Li-S batteries with the double-shelled single atom catalyst delivered the specific capacity of 702.2 mAh g -1 after 550 cycles at 1.0 C. The regional structure design and evaluation method provide a new strategy for the further development of single atom catalysts for more electrochemical processes., (© 2023 Wiley-VCH GmbH.)

Diabetic cardiomyopathy (DCM) is an important complication leading to the death of patients with diabetes, but there is no effective strategy for clinical treatments. Fufang Zhenzhu Tiaozhi (FTZ) is a patent medicine that is a traditional Chinese medicine compound preparation with comprehensive effects for the prevention and treatment of glycolipid metabolic diseases under the guidance of "modulating liver, starting pivot and cleaning turbidity". FTZ was proposed by Professor Guo Jiao and is used for the clinical treatment of hyperlipidemia. This study was designed to explore the regulatory mechanisms of FTZ on heart lipid metabolism dysfunction and mitochondrial dynamics disorder in mice with DCM, and it provides a theoretical basis for the myocardial protective effect of FTZ in diabetes. In this study, we demonstrated that FTZ protected heart function in DCM mice and downregulated the overexpression of free fatty acids (FFAs) uptake-related proteins cluster of differentiation 36 (CD36), fatty acid binding protein 3 (FABP3) and carnitine palmitoyl transferase 1 (CPT1). Moreover, FTZ treatment showed a regulatory effect on mitochondrial dynamics by inhibiting mitochondrial fission and promoting mitochondrial fusion. We also identified in vitro that FTZ could restore lipid metabolism-related proteins, mitochondrial dynamics-related proteins and mitochondrial energy metabolism in PA-treated cardiomyocytes. Our study indicated that FTZ improves the cardiac function of diabetic mice by attenuating the increase in fasting blood glucose levels, inhibiting the decrease in body weight, alleviating disordered lipid metabolism, and restoring mitochondrial dynamics and myocardial apoptosis in diabetic mouse hearts., Competing Interests: Declaration of Competing Interest Authors declared that there were no known conflicts of interest associated with this publication., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a rapidly growing epidemic that results in increased morbidity, mortality, and soaring medical costs. Prostaglandin E 2 (PGE 2 ), a vital lipid mediator, has been reported to protect against hepatic steatosis, inflammation, endoplasmic reticulum (ER) stress, and insulin resistance, indicating its potential therapeutic role in T2DM. PGE 2 can be degraded by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). SW033291, an inhibitor of 15-PGDH, has been reported to increase PGE 2 levels, however, the effect of SW033291 in T2DM remains to be explored. This study aims to evaluate whether SW033291 protects against T2DM and explore its potential mechanisms. A T2DM mouse model was established through high-fat diet/streptozotocin injection, while palmitic acid-treated mouse primary hepatocytes were used as insulin-resistant cell models. SW033291 treatment reduced body weight, fat weight, fasting blood glucose, and improved impaired glucose tolerance and insulin resistance in T2DM mice. More importantly, SW033291 alleviated steatosis, inflammation, and ER stress in the liver of T2DM mice. Mechanistically, SW033291 decreased the expressions of SREBP-1c and ACC1, and increased the expression of PPARα in T2DM mice. Additionally, SW033291 inhibited NF-κB and eIF2α/CHOP signaling in T2DM mice. Further, we showed that the protective effects of SW033291 on the above-mentioned pathophysiological processes could be hindered by inhibition of the PGE 2 receptor EP4. Overall, our study reveals a novel role of SW033291 in alleviating T2DM and suggests its potential as a new therapeutic strategy for T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Identifying the thresholds for the positive responses of total net primary productivity (NPP) to nitrogen (N) enrichment is an essential prerequisite for predicting the benefits of N deposition on ecosystem carbon sequestration. However, the responses of below-ground NPP (BNPP) to N enrichment are unknown in many ecosystems, which limits our ability to understand the carbon cycling under the scenario of increasing N availability. We examined the changes in above-ground NPP (ANPP), BNPP, and NPP of a temperate meadow steppe across a wide-ranging N addition gradient (0, 2, 5, 10, 20, and 50 g N m -2  year -1 ) during 5 years. Both ANPP and NPP increased nonlinearly with N addition rates. The N saturation threshold for ANPP (T A ) and NPP (T N ) was at the rate of 13.11 and 6.70 g N m -2  year -1 , respectively. BNPP decreased with increasing N addition when N addition rates ˃5 g N m -2  year -1 , resulting in much lower T N than T A . Soil N enrichment played a key role in driving the negative impacts of high N addition rates on BNPP, and consequently on the earlier occurrence of N saturation threshold for NPP. Our results highlight the negative effects of soil N enrichment on NPP in natural grasslands super-saturated with N. Furthermore, by considering ANPP and BNPP simultaneously, our results indicate that previous findings from above-ground might have over-estimated the positive effects of N deposition on primary productivity., (© 2023 John Wiley & Sons Ltd.)

Chitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers.