On the basis of previous studies, the low-polar part of Achyranthes aspera L. (A. aspera) had strong anti-inflammatory activity. Three compounds were isolated from the low polarity fraction of A. aspera, and their structures were identified as α-spinasterol (1), 7,8-dihydrospinasterol (2), 22,23-dihydrospinasterol (3). Among them, the content of α-spinasterol (1) in A. aspera was higher in the spring and winter seasons through HPLC methods, ranging from 0.0085 to 0.0157%. Futhermore, in the LPS-induced RAW264.7 cells inflammation model, α-spinasterol significantly reduced the levels of cytokines such as IL-6, PGE2 and TNF-α, inhibited the expression of COX-2, 5-LOX, p-IKKβ, p-NFκB and p-IkBα proteins, and promoted the expression of Nrf2, HO-1 and NQO1 proteins. Therefore, this study showed that α-spinasterol can inhibit LPS-induced RAW264.7 cells inflammation, and its mechanism may be related to the inhibition of NF-κB pathway, activation of Nrf2 pathway, and reduction of excessive release of inflammatory factors.

Chronic inflammation poses a significant threat to physical health. The increasing prevalence of skin disorders is attributed to external factors such as environmental pollution and UV-induced stress. To address damaged skin, the cosmetic market increasingly favors the development of effective products containing natural active compounds. This study constitutes the initial examination of the anti-inflammatory properties of polyphenols extracted from Sargassum pallidum. The experimental results demonstrated that SPP significantly reduced intracellular levels of nitric oxide (NO), reactive oxygen species (ROS), and multiple inflammatory mediators. Furthermore, SPP exhibited an inhibitory effect on the mRNA expression of inflammation-related genes: compared to the control group, the mRNA levels of IL-1β, IL-6, TNF-α, iNOS, and COX-2 decreased by 4.94 ± 0.72-fold, 113.64 ± 27.46-fold, 1.40 ± 0.21-fold, 11.68 ± 3.90-fold, and 0.47 ± 0.11-fold, respectively (data presented as mean ± SD, * p < 0.05). SPP was incorporated into cosmetic formulations as a natural active ingredient to create emulsions and creams. Upon assessment of various skin parameters, these formulations demonstrated significant skincare benefits. In conclusion, SPP exhibits promising anti-inflammatory properties, making it a potential natural active ingredient for applications in cosmetics.

Extracellular vesicles (EVs) play a pivotal role in intercellular communication and are closely linked to cancer progression and metastasis. Our previous studies have shown that gastric cancer cell-derived EVs can promote tumor metastasis by increasing the permeability of the endothelial barrier. However, it remains unclear which effector molecule in the EV structure is the key factor of EV-mediated tumor metastasis and the underlying molecular mechanism. In this study, we found that CD147 is a key molecule highly expressed in gastric cancer-derived EVs and confirmed the role of CD147-high EVs from gastric cancer cells in promoting endothelial dysfunction and tumor metastasis. Our results showed that CD147-high EVs activated the VEGF/AKT/eNOS/NO and AKT/mTOR/p70S6K signaling pathways, leading to endothelial cytoskeletal reorganization and internalization of VE-cadherin, which significantly compromised endothelial barrier integrity, increased vascular leakage, enhanced transendothelial migration of tumor cell, and promoted the formation of metastatic tumors. Furthermore, detection of CD147 levels in gastric cancer tissues and plasma EVs indicated that high CD147 expression was associated with advanced tumor stage, poor prognosis, and reduced survival. Our findings suggest that CD147-high EVs are critical mediators of tumor-endothelial interactions and potential diagnostic and prognostic biomarkers for gastric cancer. Their potential as therapeutic targets for gastric cancer is underscored. This figure illustrates the proposed mechanism by which CD147-high gcEVs promote tumor metastasis. CD147-high EVs are released from gastric cancer cells and interact with endothelial cells in the tumor microenvironment. Upon uptake by endothelial cells, CD147-high gcEVs activate the key signaling pathways, including the VEGF/AKT/eNOS/NO and AKT/mTOR/p70S6K pathway, which collectively facilitate the metastatic potential of gastric cancer cells by promoting endothelial cell dysfunction and increasing vascular permeability.

α-ketoglutaric acid (AKG), a tricarboxylic acid cycle metabolite central to aerobic metabolism and longevity, retains unresolved anti-aging protein targets. Here, we demonstrate that reduced isocitrate dehydrogenase 1 (IDH1) expression during senescence lowers AKG production, accelerating the aging of mesenchymal stem cells (MSCs). Exogenous AKG or IDH1 overexpression restores AKG levels, enabling 2-oxoglutarate and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1)-catalyzed hydroxylation of ribosomal protein S23 (RPS23) at proline 62. Mechanistically, AKG stabilizes the OGFOD1-RPS23 complex, enhancing translation accuracy to limit misfolded protein accumulation while sustaining synthesis rates, thereby balancing proteostasis. The natural flavonoid scutellarin (Scu), identified as an IDH1 agonist, elevates AKG to delay MSC senescence. In aged mice, Scu improves cognitive function, reduces osteoporosis and skin aging, and suppresses senescence-associated secretory phenotype. Our findings identify the AKG-IDH1-RPS23 axis as a regulator of stem cell senescence and we propose metabolic reprogramming strategies for anti-aging therapies.

Baicalin is a flavonoid of Scutellaria baicalensis Georgi. It possesses antipyretic, analgesic, and anti-inflammatory effects. It has great potential to treat gout. A network pharmacology approach, molecular docking and experimental validation were applied to investigate the pharmacological mechanisms of baicalin in treating gout.

The Gastrin/CCKBR axis is essential for inhibiting intestinal sodium absorption, but its effects on intestinal glucose metabolism remain elusive. This study aims to determine the role of intestinal Gastrin/CCKBR on glucose absorption in the development of type 2 diabetes (T2D). Intestinal epithelial cell-specific Cckbr knockout mice and control wild-type mice are fed normal diet (ND, 10% fat) or high fat diet (HFD, 60% fat) to study the effect of intestinal Gastrin/CCKBR on blood glucose levels. Gastrin-SiO2 microspheres (20 mg kg-1 d-1) are designed so that gastrin specifically stimulates intestinal CCKBR, without its absorption into the circulation. Mice with silenced intestinal Cckbr has pre-diabetes mellitus (Pre-DM) that rapidly progressed into T2D when fed HFD. Moreover, Gastrin-SiO2 microspheres markedly reduce glucose absorption in duodenum obtained from patients with T2D. In mice with HFD-induced T2D, Gastrin-SiO2 microspheres reduce intestinal glucose absorption by down-regulating intestinal SGLT1 and GLUT2 expressions and stimulating incretin secretion. This study shows the important role of intestinal Gastrin/CCKBR in intestinal glucose absorption. Gastrin-SiO2 microspheres may be a promising strategy for the treatment of patients with T2D.

The vesicular stomatitis virus (VSV)-vectored African swine fever virus (ASFV) vaccine can induce efficient immune response, but the potential mechanism remains unsolved. In order to investigate the efficacy of recombinant viruses (VSV-p35, VSV-p72)-mediated dendritic cells (DCs) maturation and the mechanism of inducing T-cell immune response, the functional effects of recombinant viruses on DC activation and target antigens presentation were explored in this study. The results showed that surface-marked molecules (CD80, CD86, CD40, and MHC-II) and secreted cytokines (IL-4, TNF-α, IFN-γ) were highly expressed in the recombinant virus-infected DCs. In addition, the co-culture results of recombinant virus-treated DCs with naive T cells showed that the Th1- and Th17-type responses were effectively activated. Taken together, the study indicated that the VSV-vectored ASFV vaccine activated the maturation of DCs and the Th1- and Th17-type immune response, which provided a theoretical basis for the development of novel ASF vaccines.

Despite growing interest in circadian disturbances as potential triggers for dementia, the specific impact of circadian syndrome (CircS) on dementia incidence remains poorly understood. Moreover, the role of genetic susceptibility modulating these effects remains to be explored.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Addressing global warming is one of the most pressing environmental challenges and a crucial agenda for humanity. In this literature study, we employed bibliometrics to reproduce nearly two decades of research on carbon emission reduction in China, the largest carbon emitter worldwide. The scientometrics analysis was conducted on 1570 academic works published between 2001 and 2021 concerning China's carbon emission reduction to characterize the knowledge landscape. Using CiteSpace and VOSviewer, the basic characteristics, research forces, knowledge base, research topic evolution, and research hotspots were identified and revealed. The analysis results show that the attention to and research on China's carbon emissions have increased in recent years, giving rise to leading institutions and relatively stable core journal groups in this field. The research disciplines are relatively concentrated, but the research collaboration needs strengthening. The research hotspots are mainly carbon emission causes, impacts, and countermeasures in China, and the research frontiers have been constantly advanced and expanded. In the future, research on countermeasures needs more effort, and research cooperation needs to strengthen. The changing landscape of hotspot clusters reveals China's transition towards a low-carbon economy. Through comprehensive analysis of the potential and obstacles to China's transition to low-carbon development, we identified three promising areas of action (low-carbon cities, low-carbon technologies and industries, and transforming China's energy system) and proposed research directions to address remaining gaps systematically.

Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders.

Disease activity evaluation is important in Crohn's disease (CD). We aimed to establish new disease activity indices for CD based on noninvasive parameters. The data of 110 patients with CD were retrospectively analyzed. Parameters from bowel ultrasound and biomarkers were measured to select the variables included in the models by univariate analysis. Logistic regression analysis was performed to predict mucosal and transmural activities defined by ileocolonoscopy or computed tomography enterography, respectively. The models' performance was measured by the area under the receiver operating characteristic (ROC) curve (AUC). Leave-one-out cross validation (LOOCV) was applied to adjust for overconfidence in the newly established score models. To predict mucosal activity, erythrocyte sedimentation rate (ESR) and (LimG × BWT)-SUM (the sum of the product of Limberg grade [LimG] and bowel wall thickness [BWT] of each bowel segment) were selected for model A, and the equation was A = 2 × ESR + 9.3 × (LimG × BWT)-SUM. The AUC of ROC, sensitivity, and specificity were 0.927%, 89.8%, and 86.4%, respectively. The AUC of the ROC curve verified by LOOCV was 0.913. To predict transmural activity, albumin (ALB) and LimG-SUM (the sum of the LimG of all the bowel segments) were selected for model B, which was established as B = -1.3 × ALB +1.7 × LimG-SUM. The AUC of ROC, sensitivity, and specificity were 0.851%, 78.0%, and 84.2%, respectively. The AUC of the ROC curve verified by LOOCV was 0.833. Nomograms were developed for two score models. New score models based on noninvasive parameters established in this study showed good abilities in detecting active disease and performed well in the validation phase.

The paper aimed to investigate the effect of miR186-5p on invasion and migration of breast cancer cells and its molecular mechanism. MicroRNA-186-5p was found to be low expressed in breast cancer and highly expressed in SBEM by bioinformatics analysis. After transfecting MDA-MB-231 cells with miR-186-5p inhibitor NC, miR-186-5p inhibitor, miR-186-5p mimic NC and miR-186-5p mimic, respectively. The migration and invasive ability of breast cancer cells were detected by cell scratch test and Transwell test. Moreover, after adding 740 Y-P to the miR-186-5p mimic NC group and miR-186-5p mimic group cells, SBEM and PI3K pathway-related proteins were detected by Western blotting and proliferation of the cancer cells was evaluated by monoclonal cell experiment. Meanwhile, exogenous miR-186-5p mimic in MDA-MB-231 cells significantly inhibited the expression of SBEM, p-PI3K, p-AKT and their downstream pathways, MMP1, MMP3, MMP9, CyclinD1, PCNA and CyclinB1 proteins and reduced proliferation of breast cancer cells. Furthermore, the expression of SBEM protein in the miR-186-5p mimic + 740Y-P group was significantly lower than the miR-186-5p mimic NC + 740Y-P group after adding 740 Y-P. However, there were no significant changes in the protein's levels associated with PI3K pathway and the cancer cells proliferation. These results suggest that low expression of miR-186-5p in breast cancer results in an abnormally high expression of SBEM, activation of PI3K/AKT signaling pathway, promoting migration and invasion of human breast cancer cells.

Renal fibrosis (RF) is a common pathological feature of chronic kidney disease (CKD), which remains a major public health problem. As now, there is still lack of chemical or biological drugs to reverse RF. Shen-shuai-yi Recipe (SSYR) is a classical Chinese herbal formula for the treatment of CKD. However, the effects and mechanisms of SSYR in treating RF are still not clear. In this study, the active constituents SSYR for treating RF were explored by UHPLC-Q-Orbitrap HRMS. Bioinformatics analyses were employed to analyze the key pharmacological targets and the core active constituents of SSYR in the treatment of RF. In experimental validation, vehicle or SSYR at doses of 2.12 g/kg/d and 4.25 g/kg/d were given by orally to unilateral ureteric obstruction (UUO) mice. 13 days after treatment, we detected the severity of renal fibrosis, extracellular collagen deposition and pre-fibrotic signaling pathways. Bioinformatics analysis suggested that signal transducer and activator of transcription 3 (STAT3) was the core target and lenticin, luteolin-7-O-rutinoside, hesperidin, kaempferol-3-O-rutinoside, and 3,5,6,7,8,3',4'-heptamethoxyflavone were the key constituents in SSYR for treating RF. SSYR significantly reduced the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), collagen-I and alleviated renal interstitial collagen deposition in UUO kidneys. In mechanism, SSYR potently blocked the phosphorylation of STAT3 and Smad3 and suppressed the expression of connective tissue growth factor (CTGF). Collectively, SSYR can ameliorate RF via inhibiting the phosphorylation of STAT3 and its downstream and reducing the collagen deposition, suggesting that SSYR can be developed as a novel medicine for treating RF.

Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of matched esophageal squamous cell carcinoma (ESCC) and normal tissue samples as well as two cell lines were analyzed. AS events with significant differences were identified between ESCC and matched normal tissues, which were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events were found. Of these, 6019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues, as well in the two cell lines were found. Four pathways and 20 biological processes related to pro-metastasis cell junction and migration were significantly enriched for the differentially spliced genes. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Differentially spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1 are shown with a sashimi plot. These results suggest that cell junction- and migration-related biological processes are influenced by AS abnormalities, and aberrant splicing events can be affected by splicing factor expression changes. The involved splicing factor SF3B4 was found to be a survival-related gene in ESCC and is presumed to regulate AS in multiple cancers. In summary, we identified significant differentially expressed AS events which may be related to the development of ESCC.

Lung cancer, a major contributor to cancer-related fatalities worldwide, involves a complex pathogenesis. Cathepsins, lysosomal cysteine proteases, play roles in various physiological and pathological processes, including tumorigenesis. Observational studies have suggested an association between cathepsins and lung cancer. However, the causal link between the cathepsin family and lung cancer remains undetermined. This study employed Mendelian randomization analyses to investigate this causal association. The univariable Mendelian randomization analysis results indicate that elevated cathepsin H levels increase the overall risk of lung cancer, adenocarcinoma, and lung cancer among smokers. Conversely, reverse Mendelian randomization analyses suggest that squamous carcinoma may lead to increased cathepsin B levels. A multivariable analysis using nine cathepsins as covariates reveals that elevated cathepsin H levels lead to an increased overall risk of lung cancer, adenocarcinoma, and lung cancer in smokers. In conclusion, cathepsin H may serve as a marker for lung cancer, potentially inspiring directions in lung cancer diagnosis and treatment.

Rationale: Liver resection and transplantation surgeries are accompanied by hepatic ischemia-reperfusion (HIR) injury that hampers the subsequent liver recovery. Given that the liver is the main organ for metabolism and detoxification, ischemia-reperfusion in essence bestows metabolic stress upon the liver and disrupts local metabolic and immune homeostasis. Most of the recent and current research works concerning HIR have been focusing on addressing HIR-induced hepatic injury and inflammation, instead of dealing with the metabolic reprogramming and restoration of redox homeostasis. As our previous work uncovers the importance of 5-aminolevulinate (5-ALA) synthesis during stress adaptation, here we evaluate the effects of supplementing 5-ALA to mitigate HIR injury. Methods: 5-ALA was supplemented into the mice or cultured cells during the ischemic or oxygen-glucose deprivation (OGD) phase. Following reperfusion or reoxygenation, cellular metabolism and energy homeostasis, mitochondrial production of reactive oxygen species (ROS) and transcriptomic changes were evaluated in HIR mouse models or cultured hepatocytes and macrophages. Liver injury, hepatocytic functional tests, and macrophagic M1/M2 polarization were assessed. Results: Dynamic changes in the expression of key enzymes in 5-ALA metabolism were first confirmed in donor and mouse liver samples following HIR. Supplemented 5-ALA modulated mouse hepatic lipid metabolism and reduced ATP production in macrophages following HIR, resulting in elevation of anti-inflammatory M2 polarization. Mechanistically, 5-ALA down-regulates macrophagic chemokine receptor CX3CR1 via the repression of RelA following OGD and reoxygenation (OGD/R). Cx3cr1 KO mice demonstrated milder liver injuries and more macrophage M2 polarization after HIR. M2 macrophage-secreted chitinase-like protein 3 (CHIL3; CHI3L1 in human) is an important HIR-induced effector downstream of CX3CR1 deficiency. Addition of CHIL3/CHI3L1 alone improved hepatocellular metabolism and reduced OGD/R-inflicted injuries in cultured mouse and human hepatocytes. Combined treatment with 5-ALA and CHIL3 during the ischemic phase facilitated lipid metabolism and ATP production in the mouse liver following HIR. Conclusion: Our results reveal that supplementing 5-ALA promotes macrophagic M2 polarization via downregulation of RelA and CX3CR1 in mice following HIR, while M2 macrophage-produced CHIL3/CHI3L1 also manifests beneficial effects to the recovery of hepatic metabolism. 5-ALA and CHIL3/CHI3L1 together mitigate HIR-induced mitochondrial dysfunction and hepatocellular injuries, which may be developed into safe and effective clinical treatments to attenuate HIR injuries.

Angelica Yinzi (AYZ) is a Chinese traditional herbal formula reported to attenuate itches and inflammation caused by atopic dermatitis (AD). However, the underlying mechanism of AYZ in the attenuation of itchiness and inflammation remains unknown.

Hormographiella aspergillata is a rare and emerging cause of invasive mould infections in patients with haematological malignancies, with a mortality rate of approximately 70%. Here, we present the first reported case of suspected disseminated H. aspergillata infection in China. The patient experienced a second relapse of acute myeloid leukaemia and developed neutropenia, fever, discrepant blood pressure between limbs, and cutaneous lesions limited to the left upper extremity. Since lung tissue biopsy was not feasible, metagenomic next-generation sequencing (mNGS) and panfungal polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid and blood samples were performed, which indicated probable H. aspergillata pulmonary infection. Histopathology of cutaneous lesions revealed numerous fungal hyphae within dermal blood vessels. mNGS of a skin biopsy sample identified H. aspergillata sequences, and the fungi was subsequently recovered from fungal culture, proving cutaneous H. aspergillata infection. Despite combined antifungal therapy, the patient died owing to disease progression. Additionally, 22 previously reported cases of invasive H. aspergillata infection were reviewed in patients with haematological malignancies. Thus, mNGS is a powerful diagnostic tool for the early and effective detection of invasive H. aspergillata infections, with the advantage of sequencing all potential pathogens, and providing results within 24 h.

The present study aimed to investigate the regulation of miR-25-3p on macrophage autophagy and its effect on macrophage clearance of intracellular Mycobacterium bovis Bacillus Calmette-Guerin (BCG) retention based on the previous findings on the differential expression of exosomal miRNA in macrophages infected with BCG.