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ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.

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Structural Fe in phyllosilicates represents a crucial and potentially renewable reservoir of electron equivalents for contaminants reduction in aquatic and soil systems. However, it remains unclear how in-situ modification of Fe redox states within Fe-bearing phyllosilicates, induced by electron shuttles such as naturally occurring organics, influences the fate of contaminants. Herein, this study investigated the processes and mechanism of Cr(VI) reduction on two typical Fe(II/III)-bearing phyllosilicates, biotite and chlorite, in the presence of cysteine (Cys) at circumneutral pH. The experimental results demonstrated that Cys markedly enhanced the rate and extent of Cr(VI) reduction by biotite/chlorite, likely because of the formation of Cr(V)-organic complexes and consequent electron transfer from Cys to Cr(V). The concomitant production of non-structural Fe(II) (including aqueous Fe(II), surface bound Fe(II), and Cys-Fe(II) complex) cascaded transferring electrons from Cys to surface Fe(III), which further contributed to Cr(VI) reduction. Notably, structural Fe(II) in phyllosilicates also facilitated Cr(VI) reduction by mediating electron transfer from Cys to structural Fe(III) and then to edge-sorbed Cr(VI). 57Fe Mössbauer analysis revealed that cis-coordinated Fe(II) in biotite and chlorite exhibits higher reductivity compared to trans-coordinated Fe(II). The Cr end-products were insoluble Cr(III)-organic complex and sub-nanometer Cr2O3/Cr(OH)3, associated with residual minerals as micro-aggregates. These findings highlight the significance of in-situ produced Fe(II) from Fe(II/III)-bearing phyllosilicates in the cycling of redox-sensitive contaminants in the environment.

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Essential oil of Acorus tatarinowii Schott (ATEO) have significant biological activity, but their physical and chemical properties are unstable and susceptible to interference by external factors, resulting in oxidation, decomposition, and isomerization of essential oils (EOs), ultimately diminishing the quality of EOs and escalating clinical risks. In this research, based on the concept of " combination of medicine and adjuvant, " the unsuitable stabilizer Cinnabaris in Lingzhu powder prescription was modified with a SiO2 surface to become a stabilizer suitable for Pickering emulsion. The modified Cinnabaris was synthesized, with a focus on exploring the surface modification of Cinnabaris to facilitate its role as a stabilizer in Pickering emulsion. Thermal stability studies showed that modified Cinnabaris-stabilized emulsion had higher EOs retention and lower peroxide value and hydrogen peroxide content. GC-MS analysis showed that the volatile components in the emulsion were more stable than the EOs. In vitro dissolution experiments showed that in the dissolution medium of artificial gastric juice and artificial intestinal juice, compared with the ATEO, the release in Pickering emulsion was faster within 48 h, indicating that the ATEO had been encapsulated in Pickering emulsion, which could improve the in vitro dissolution rate of EOs. This study convincingly demonstrates the potential of modified Cinnabaris-stabilized Pickering emulsion to improve the thermal stability and in vitro dissolution rate of EOs.

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In recent years, there has been a surge in the popularity of fasting as a method to enhance one's health and overall well-being. Fasting is a customary practice characterized by voluntary refraining from consuming food and beverages for a specified duration, ranging from a few hours to several days. The potential advantages of fasting, including enhanced insulin sensitivity, decreased inflammation, and better cellular repair mechanisms, have been well documented. However, the effects of fasting on cancer therapy have been the focus of recent scholarly investigations. Doxorubicin (Dox) is one of the most widely used chemotherapy medications for cancer treatment. Unfortunately, cardiotoxicity, which may lead to heart failure and other cardiovascular issues, has been linked to Dox usage. This study aims to comprehensively examine the possible advantages and disadvantages of fasting concerning Dox-induced cardiotoxicity. Researchers have investigated the potential benefits of fasting in lowering the risk of Dox-induced cardiac damage to solve this problem. Nevertheless, new studies indicate that prolonged alternate-day fasting may adversely affect the heart's capacity to manage the cardiotoxic properties of Dox. Though fasting may benefit overall health, it is essential to proceed cautiously and consider the potential risks in certain circumstances.

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Severe fever with thrombocytopenia syndrome (SFTS) is a widespread infectious disease with high mortality. Hence, identifying valuable biomarkers for detecting the early changes in SFTS is crucial. In this study, we investigated the relationship between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT-ALB) and the prognosis of patients with SFTS virus infection. After excluding the patients who did not meet the SFTS diagnostic criteria, those with SFTS from the First Affiliated Hospital of Wannan Medical College were divided into a fatal and Nonfatal group based on their disease prognosis. A dynamic analysis of the daily laboratory data was conducted for 14 days following SFTS onset. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HCT-ALB. Another sample of patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University was utilized to verify the study conclusions. A total of 158 patients with SFTS were included. Among them, 126 patients were categorized in the Nonfatal group and 32 in the fatal group, leading to a mortality rate of 20.25% (32/158). Univariate analysis of the laboratory test findings and ROC curve analysis showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCT-ALB, and lactate dehydrogenase (LDH) had a relatively better ability to discriminate the disease condition of the patients with SFTS. Moreover, HCT-ALB served as a predictor of SFTS prognosis. Additionally, an area under the ROC curve (AUC) of 0.777 and a critical HCT-ALB value of 4.75 on day 7 were associated with a sensitivity of 83.3% and a specificity of 73.9%. On day 8 (AUC = 0.882), the critical value of HCT-ALB was 9.25, while the sensitivity was 100% and specificity was 76.5%. Further verification based on the data of 91 patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University demonstrated a mortality rate of 51% (24/47) among those with HCT-ALB values >4.75 on day 7 of the disease course, highlighting the potential of the HCT-ALB value of >4.75 for predicting SFTS prognosis. High HCT-ALB values are closely related to the mortality of patients with SFTS. HCT-ALB is a sensitive and independent predictor of early disease in patients with SFTS.

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Background: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear. Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry. Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1ß and ROS, inhibiting COX-2 and iNOS protein expression in cells(p<0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p<0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting. Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway.

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BACKGROUND: Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk and all-cause mortality in patients with CRC remain unclear. METHODS: We analyzed the association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. RESULTS: Compared to the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% CI: 36.16-42.32) of CRC incident cases. Meanwhile, a significant association between the AL and all-cause mortality in patients with CRC was found, with a HR of 1.71 (95% CI: 1.16-2.50) for the fourth quartile compared to the AL score in the first quartile, demonstrating a positive dose-response relationship. CONCLUSION: High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.

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Coronary heart disease is a prevalent cardiovascular ailment globally, with myocardial infarction (MI) being one of its most severe manifestations. The morbidity and mortality of MI are escalating, showing an increasing trend among younger, highly educated individuals, thereby posing a serious threat to public health. Currently, thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting are the primary clinical treatments for MI. Although these methods significantly reduce patient mortality, complications often result in poor prognoses. Due to limitations in chemical synthetic drug research, the focus has shifted towards developing herbs based on natural substances. Natural medicines represent a novel approach for safer and more effective MI management and treatment. They can control multiple pathogenic variables by targeting various pathways and systems. This paper investigates the molecular mechanisms of MI and evaluates the application of natural products and medicinal plants in MI treatment over the past 5 years, demonstrating their specific good therapeutic potential and superior tolerance. These natural therapies have been shown to mitigate myocardial cell damage caused by MI through mechanisms such as oxidative stress, inflammation, apoptosis, angiogenesis, myocardial fibrosis, autophagy, endoplasmic reticulum stress, mitophagy, and pyroptosis. This review offers the latest insights into the application of natural products and medicinal plants in MI treatment, elucidating their mechanisms of action and serving as an important reference for MI prevention.

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Mass cytometry is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level, advancing clinical research in immune monitoring. Nevertheless, the vast data generated by cytometry by time-of-flight (CyTOF) poses a significant analytical challenge. To address this, we describe ImmCellTyper (https://github.com/JingAnyaSun/ImmCellTyper), a novel toolkit for CyTOF data analysis. This framework incorporates BinaryClust, an in-house developed semi-supervised clustering tool that automatically identifies main cell types. BinaryClust outperforms existing clustering tools in accuracy and speed, as shown in benchmarks with two datasets of approximately 4 million cells, matching the precision of manual gating by human experts. Furthermore, ImmCellTyper offers various visualisation and analytical tools, spanning from quality control to differential analysis, tailored to users' specific needs for a comprehensive CyTOF data analysis solution. The workflow includes five key steps: (1) batch effect evaluation and correction, (2) data quality control and pre-processing, (3) main cell lineage characterisation and quantification, (4) in-depth investigation of specific cell types; and (5) differential analysis of cell abundance and functional marker expression across study groups. Overall, ImmCellTyper combines expert biological knowledge in a semi-supervised approach to accurately deconvolute well-defined main cell lineages, while maintaining the potential of unsupervised methods to discover novel cell subsets, thus facilitating high-dimensional immune profiling.

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BACKGROUND: An increased risk of diabetes mellitus (DM) after COVID-19 has been reported in the United States, Europe, and Asia. The burden of COVID-related DM has yet to be described in Africa, where the overall risk of DM has been increasing rapidly. Our objective was to compare the prevalence of pre-DM and DM in Nigerian individuals with a history of COVID-19 to individuals without known COVID-19 infection. METHODS: We undertook a retrospective cohort study with 256 individuals with a past medical history of COVID-19 with no history of pre-DM or DM and 256 individuals without a history of COVID-19 or pre-DM/DM. Participants were categorized as pre-DM (fasting capillary glucose 100-125 mg/dL) or DM (fasting capillary glucose ≥ 126 mg/dL). We employed univariate and multivariable logistic regression to identify key predictors and adjust for confounders related to hyperglycaemia risk factors. Additionally, we used multinomial logistic regression to analyze the relationship between COVID-19 history and diabetes status, distinguishing between normal, pre-diabetic, and diabetic glucose levels. All models were adjusted for age, gender, hypertension, physical activity, central adiposity, and family history of DM. RESULTS: Compared to the control group, those with a history of COVID-19 had a similar median age (38 vs. 40 years, p = 0.84), had a higher proportion of men (63% vs. 49%), and had a lower prevalence of central adiposity (waist: hip ratio ≥ 0.90 for males and WHR ≥ 0.85 for females) (48% vs. 56.3%, p = 0.06). Of the 256 with a history of COVID-19, 44 (17%) required in-patient care. The median (interquartile range) time interval between COVID-19 diagnosis and the glycaemic assessment was 19 (IQR: 14, 24) months. Pre-DM prevalence was 27% in the post-COVID-19 group and 4% in the control group, whereas the prevalence of DM was 7% in the post-COVID-19 group and 2% in the control group. After multivariable adjustment, the odds of pre-DM were 8.12 (95% confidence interval (CI): 3.98, 16.58; p < 0.001) higher, and the odds of DM were 3.97 (95% CI: 1.16, 13.63) higher in those with a history of COVID-19 compared to controls. In the adjusted multinomial logistic regression analysis, individuals with a history of COVID-19 exhibited significantly elevated risks for pre-diabetes (RRR = 7.55, 95% CI: 3.76-15.17) and diabetes (RRR = 3.44, 95% CI: 1.01-11.71) compared to those without COVID-19. CONCLUSION: Previous COVID-19 was found to be a risk factor for prevalent pre-diabetes and diabetes mellitus in Nigeria. More intensive screening for DM in those with a history of COVID-19 should be considered.

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The unavoidable residual tumor tissue from surgery and the strong aggressiveness of tumor cells pose challenges to the postoperative treatment of tumor patients, accompanied by in situ tumor recurrence and decreased quality of life. Therefore, there is an urgent need to explore appropriate postoperative therapeutic strategies to remove residual tumor cells after surgery to inhibit tumor recurrence and metastasis after surgery. In recent years, with the rapid development of biomedical materials, the study of local delivery systems as postoperative delivery of therapeutic agents has gradually attracted the attention of researchers. Injectable in situ-forming hydrogel is a locally administered agent injected in situ as a solution that can be loaded with various therapeutic agents and rapidly gels to form a semi-solid gel at the treatment site. This type of hydrogel tightly fills the surgical site and covers irregular excision surfaces. In this paper, we review the recent advances in the application of injectable in situ-forming hydrogels in postoperative therapy, focusing on the matrix materials of this type of hydrogel and its application in the postoperative treatment of different types of tumors, as well as discussing the challenges and prospects of its clinical application.

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Schisandra chinensis (Turcz) Baill (S. chinensis) is the key traditional Chinese medicine for the treatment of asthma used by ancient and modern medical practitioners. However, the material basis and the main mechanism of its antiasthmatic effect remain unclear. Our preliminary results showed that schisandrol A (SCA), a representative monomer of Schisandra lignans, had the best relaxation effect on tracheal rings in isolated rats. In this research, a mouse asthma model was prepared by combining ovalbumin (OVA) with Al (OH)3 for exploring the antiasthmatic action and the underlying mechanism of SCA. The study results demonstrated that SCA improved the behavior of mice with asthma and pathological changes in their lung tissues and airways, decreased serum immunoglobulin E (IgE) and OVA-IgE levels, interleukin-4 (IL-4), IL-5, IL-13, and eotaxin contents, and leukocytes number in bronchoalveolar lavage fluid. SCA downregulated the gene expressions of keratinocyte-derived protein chemokines and ILs and reduced the expressions of phosphorylated IκB kinase α (p-IKKα) and p-nuclear factor kappa-B (NF-κB) proteins in lung tissues. In addition, it was found that SCA could significantly increase T-superoxide dismutase and catalase activities, decrease malondialdehyde content, and elevate p-IκBα, NF-E2-related-factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expressions. In summary, SCA treatment resulted in a significant improvement in the allergic bronchial asthma in mice, and its mechanisms may involve the regulation of the NF-κB/IκBα pathway to reduce inflammatory response and the Nrf2/HO-1 pathway to improve the body's antioxidant capacity. These results suggest that SCA is a key component of S. chinensis in exerting antiasthmatic effects.

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Point-of-care (POC) nanosensors with high screening efficiency show promise for user-friendly manipulation in the ever-increasing on-site analysis demand for illness diagnosis, environmental monitoring, and food safety. Currently, inspired by the merits of integrating advanced nanomaterials, molecular biology, machine learning, and artificial intelligence, lateral flow immunoassay (LFIA)-based POC nanosensors have been devoted to satisfying the commercial demands in terms of sensitivity, specificity, and practicality. Herein, we examine the use of multidimensional enhanced LFIA in various fields over the past two decades, focusing on introducing advanced nanomaterials to improve the acquisition capability of small order of magnitude targets through engineering transformations and emphasizing interdomain fusion to collaboratively address the inherent challenges in current commercial applications, such as multiplexing, development of detectors for quantitative analysis, more practical on-site monitoring, and sensitivity enhancement. Specifically, this comprehensive review encompasses the latest advances in comprehending LFIA with an alternative signal transduction pattern, aiming to achieve rapid, ultrasensitive, and "sample-to-answer" available options with progressive applications for POC nanosensors. In summary, through the cross-collaboration development of disciplines, LFIA has the potential to break the barriers toward commercialization and achieve laboratory-level POC nanosensors, thus leading to the emergence of the next generation of LFIA.

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In today's society, heavy metal ions and antibiotic contaminants have caused great harm to water systems and human health. In this study, six isostructural lanthanide metal-organic frameworks [Ln(H3imda)2(TPA)(H2O)2](Tb for CUST-881, Eu for CUST-882, Dy for CUST-883, Er for CUST-884, Nd for CUST-885, Sm for CUST-886) were constructed by selecting terephthalic acid (TPA) and 4,5-Imidazoledicarboxylic acid (H3imda) and lanthanide metal ions via solvethermal method. Among them, CUST-881 and CUST-882 can selectively detect Fe3+, Cr2O72-, CrO42, and ceftriaxone sodium (CRO) in water systems and uric acid in urine. CUST-881 shows very low detection limits for these five substances. Furthermore, Principal Component Analysis (PCA) was used to distinguish Fe3+, Cr2O72-, CrO42-, and CRO in water. To our knowledge, this is the first time that they have been able to be simultaneously distinguished. In addition, the possible sensing mechanism was studied through UV-visible spectroscopy, Infrared spectroscopy, and PXRD analysis. Furthermore, the probe also showed satisfactory repeatability and recovery when applied to UA samples that simulated urine. Based on the above results, lanthanide metal-organic frameworks have great potential for practical monitoring of contaminants in water environments.

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Background: We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment. Methods: For this prospective multicenter clinical study, HER2-positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan-Meier method was used to generate survival curves. The log-rank test was used to compare progression-free survival (PFS) between the two groups. Results: A total of 59 HER2-positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively. Conclusions: For metastatic HER2-positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway-activated metastatic HER2-positive breast cancer patients.

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BACKGROUND: Influenza virus-induced pneumonia (IVP) is an infectious pulmonary disease characterized by exacerbated pulmonary inflammation caused by invasion of the influenza virus. IVP continues to threaten public health due to its high morbidity and mortality rates. Geniposide is one of the major bioactive constituents of G. jasminoides, which exerts antiviral and anti-inflammatory effects on influenza A virus (IAV) infection. PURPOSE: To investigate therapeutic effects and comprehensive mechanisms of geniposide on IAV infection and subsequent pneumonia. METHODS: ICR mice were infected intranasally with H1N1 (A/FM/1/47) to detect the anti-IAV activity of geniposide. Proteomics combined with function-integrated analysis were conducted to gain insight into the comprehensive mechanisms of geniposide. Subsequently, western blot was used to detect the phosphorylation of signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2), Interferon regulatory factor 9 (IRF9) and Janus kinase 1 (JAK1) in Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in lung tissue. Finally, RT-qPCR was used to detect the levels of interleukin 6 (IL-6), interleukin 17 (IL-17), interferon-γ (IFN-γ) and the STAT1 inhibitor (fludarabine) was used to verify the targeting between STAT1 and geniposide in RAW cells. RESULTS: Geniposide could significantly reduce the lung index, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by IAV infection. A total of 411 differentially expressed proteins were identified among control, model, and geniposide-treated group in proteomic analysis. According to function-integrated analysis, 15 KEGG pathways were enriched and divided into 9 groups (modules), including influenza A, NOD-like receptor signaling, RIG-I-like receptor signaling, and so on. Among these modules, the most intensely interacting module pair was the NOD-like receptor signaling and influenza A, in which STAT1 and STAT2 acted as hubs with critical bridgeness role in the target network of geniposide. This indicated that geniposide may mitigate inflammation and alleviate IVP by JAK/STAT signaling pathways. Moreover, validation experiments confirmed that geniposide can significantly inhibit STAT1 and STAT2 phosphorylation as well as down-regulated expression of IL-6, IFN-γ and IL-17 in lung. Furthermore, when RAW cells were treated with the STAT1 inhibitor (fludarabine), the inhibitory effect of geniposide on IFN-γ and IL-6 was attenuated significantly. CONCLUSIONS: Geniposide can attenuate IAV-induced pneumonia by regulating inflammatory cytokines production through the JAK/STAT pathway.

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Electrocatalytic CO2 reduction reaction (CO2RR) is a process in which CO2 is reduced to high-value-added C1 and C2 energy sources, particularly ethylene (C2H4), thereby supporting carbon-neutral recycling with minimal consumption. This makes it a promising technology with significant potential. Nevertheless, the low selectivity for C2H4 remains a significant challenge in practical applications. In this paper, a strategy based on Cu-Sn bimetallic catalysts is proposed to improve the selectivity of electrocatalytic conversion of CO2 to C2H4 over Cu-based catalysts. The experimental results show that the Faradaic efficiency (FE) of C2H4 can reach up to 48.74 %, and the FE of C2 product reaches 60 %, at which time the local current density is 11.99 mA/cm2. Compared with pure Cu catalyst, the FE and local current density of C2H4 increased by 55.27 % and 35.33 %, respectively. Moreover, the FE of C2H4 remained above 40 % after 8 h over Cu10-Sn catalyst. The addition of Sn facilitates the transfer of local electrons from Cu to Sn, stabilizes the *CO intermediate, promotes CC coupling, significantly lowers the reaction energy barrier, and enables highly efficient CO2RR catalysis for C2H4 production.

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Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.

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