Supramolecular channels via crown ether functionalized polyaniline for proton-self-doped cathode in aqueous zinc-ion battery.

Polyaniline (PANI) has been widely used as a cathode in aqueous zinc-ion batteries (AZIBs) because of its attractive conductivity and energy storage capability. However, the extensive application of PANI is limited by spontaneous deprotonation and slow diffusion kinetics. Herein, an 18-crown-6-functionalised PANI pseudorotaxane (18C6@PANI) cathode is successfully developed through a facile template-directed polymerisation reaction. The 18C6@PANI cathode exhibits a high specific capacity of 256 mAh g-1 at 0.2 A/g, excellent rate performance of 134 mAh g-1 at 6 A/g and outstanding cycle stability at a high current density of 3 A/g over 10,000 cycles. Experimental and theoretical analyses demonstrate the formation of the -N-Zn-O- structure. The abundant supramolecular channels in pseudorotaxane, induced by crown ether functional groups, are beneficial for achieving superior cyclability and rate capability. These encouraging results highlight the potential for designing more efficient PANI-based cathodes for high-performance AZIBs.

Safety assessment of Acori Tatarinowii Rhizoma: acute and subacute oral toxicity.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel.

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

BACKGROUND: Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. METHODS: A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. RESULTS: Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). CONCLUSIONS: Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Rheumatoid Arthritis Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Radiation-Induced De Novo Defects in Metal-Organic Frameworks Boost CO2 Sorption.

Defects in metal-organic frameworks (MOFs) can significantly change their local microstructures, thus notably leading to an alteration-induced performance in sorption or catalysis. However, achieving de novo defect engineering in MOFs under ambient conditions without the scarification of their crystallinity remains a challenge. Herein, we successfully synthesize defective ZIF-7 through 60Co gamma ray radiation under ambient conditions. The obtained ZIF-7 is defect-rich but also has excellent crystallinity, enhanced BET surface area, and hierarchical pore structure. Moreover, the amount and structure of these defects within ZIF-7 were determined from the two-dimensional (2D) 13C-1H frequency-switched Lee-Goldburg heteronuclear correlation (FSLG-HETCOR) spectra, continuous rotation electron diffraction (cRED), and high-resolution transmission electron microscopy (HRTEM). Interestingly, the defects in ZIF-7 all strongly bind to CO2, leading to a remarkable enhancement of the CO2 sorption capability compared with that synthesized by the solvothermal method.

Advances in Phytochemistry and Modern Pharmacology of Saposhnikovia Divaricata (Turcz.) Schischk.

Saposhnikovia divaricata (Turcz.) Schischk (S. divaricata, Fangfeng) is a herb in the Apiaceae family, and its root has been used since the Western Han Dynasty (202 B.C.). Chromones and coumarins are the pharmacologically active substances in S. divaricata. Modern phytochemical and pharmacological studies have demonstrated their antipyretic, analgesic, anti-inflammatory, antioxidant, anti-tumor, and anticoagulant activities. Technological and analytical strategy theory advancements have yielded novel results; however, most investigations have been limited to the main active substances-chromones and coumarins. Hence, we reviewed studies related to the chemical composition and pharmacological activity of S. divaricata, analyzed the developing trends and challenges, and proposed that research should focus on components' synergistic effects. We also suggested that, the structure-effect relationship should be prioritized in advanced research.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

INTRODUCTION: Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short-term and long-term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. METHODS: A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block-design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. RESULTS: When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain-regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. CONCLUSION: Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain-related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity.

Loss of USP22 alleviates cardiac hypertrophy induced by pressure overload through HiF1-α-TAK1 signaling pathway.

Ubiquitin-specific protease 22 (USP22) is a member of the ubiquitin specific protease family (ubiquitin-specific protease, USPs), the largest subfamily of deubiquitinating enzymes, and plays an important role in the treatment of tumors. USP22 is also expressed in the heart. However, the role of USP22 in heart disease remains unclear. In this study, we found that USP22 was elevated in hypertrophic mouse hearts and in angiotensin II (Ang II)-induced cardiomyocytes. The inhibition of USP22 expression with adenovirus significantly rescued hypertrophic phenotype and cardiac dysfunction induced by pressure overloaded. Consistent with in vivo study, silencing by USP22 shRNA expression in vitro had similar results. Molecular analysis revealed that transforming growth factor-ß-activating protein 1 (TAK1)-(JNK1/2)/P38 signaling pathway and HIF-1α was activated in the Ang II-induced hypertrophic cardiomyocytes, whereas HIF-1α expression was decreased after the inhibition of USP22. Inhibition of HIF-1α expression reduces TAK1 expression. Co-immunoprecipitation and ubiquitination studies revealed the regulatory mechanism between USP22 and HIF1α.Under hypertrophic stress conditions, USP22 enhances the stability of HIF-1α through its deubiquitination activity, which further activates the TAK1-(JNK1/2)/P38 signaling pathway to lead to cardiac hypertrophy. Inhibition of HIF-1α expression further potentiates the in vivo pathological effects caused by USP22 deficiency. In summary, this study suggests that USP22, through HIF-1α-TAK1-(JNK1/2)/P38 signaling pathway, may be potential targets for inhibiting pathological cardiac hypertrophy induced by pressure overload.

Bavachinin Ameliorates Rheumatoid Arthritis Inflammation via PPARG/PI3K/AKT Signaling Pathway.

Bavachinin (BVC) is a natural small molecule from the Chinese herb Fructus Psoraleae. It exhibits numerous pharmacological effects, including anti-cancer, anti-inflammation, anti-oxidation, anti-bacterial, anti-viral, and immunomodulatory properties. BVC may serve as a novel drug candidate for the treatment of rheumatoid arthritis (RA). Nevertheless, the effects and mechanisms of BVC against RA are still unknown. BVC targets were selected by Swiss Target Prediction and the PharmMapper database. RA-related targets were collected from the GeneCards, OMIM, DrugBank, TTD, and DisGeNET databases. PPI network construction and enrichment analysis were conducted by taking the intersection target of BVC targets and RA-related targets. Hub targets were further screened using Cytoscape and molecular docking. MH7A cell lines and collagen-induced arthritis (CIA) mice were used to confirm the preventive effect of BVC on RA and its potential mechanism. Fifty-six RA-related targets of BVC were identified through databases. These genes were primarily enriched in PI3K/AKT signaling pathway according to KEGG enrichment analysis. Molecular docking analysis suggested that BVC had the highest binding energy with PPARG. The qPCR and western blotting results showed that BVC promoted the expression of PPARG at both the mRNA level and protein level. Western blotting indicated that BVC might affect MH7A cell functions through the PI3K/AKT pathway. Furthermore, treatment with BVC inhibited the proliferation, migration, and production of inflammatory cytokines in MH7A cells and induced cell apoptosis to a certain extent. In vivo, BVC alleviated joint injury and inflammatory response in CIA mice. This study revealed that BVC may inhibit the proliferation, migration, and production of inflammatory cytokines in MH7A cells, as well as cell apoptosis through the PPARG/PI3K/AKT signaling pathway. These findings provide a theoretical foundation for RA therapy.

Emerging roles of air pollution and meteorological factors in autoimmune eye diseases.

Autoimmune eye diseases (AEDs), a collection of autoimmune inflammatory ocular conditions resulting from the dysregulation of immune system at the ocular level, can target both intraocular and periorbital structures leading to severe visual deficit and blindness globally. The roles of air pollution and meteorological factors in the initiation and progression of AEDs have been increasingly attractive, among which the systemic and local mechanisms are both involved in. Exposure to excessive air pollution and extreme meteorological conditions including PM2.5/PM0.1, environmental tobacco smoke, insufficient sunshine, and high temperature, etc., can disturb Th17/Treg balance, regulate macrophage polarization, activate neutrophils, induce systemic inflammation and oxidative stress, decrease retinal blood flow, promote tissue fibrosis, activate sympathetic nervous system, adversely affect nutrients synthetization, as well as induce heat stress, therefore may together deteriorate AEDs. The crosstalk among inflammation, oxidative stress and dysregulated immune system appeared to be prominent. In the present review, we will concern and summarize the potential mechanisms underlying linkages of air pollution and meteorological factors to ocular autoimmune and inflammatory responses. Moreover, we concentrate on the specific roles of air pollutants and meteorological factors in several major AEDs including uveitis, Graves' ophthalmopathy (GO), ocular allergic disease (OAD), glaucoma, diabetic retinopathy (DR), etc.

The characteristics of serum lipid spectrum in PanNENs and its correlation with clinicopathological features and prognosis.

Background: The role of dyslipidemia in pancreatic neuroendocrine tumors (PanNENs) is unclear. The aim of this study is to analyze the characteristics of serum lipid spectrum in PanNENs, and the effect of the variation in lipid profile on the development of PanNENs clinicopathological features and prognosis. Methods: All PanNENs patients between November 2012 and September 2020 in the authors' research center were identified from patient medical records and databases. A total of 185 with PanNENs patients were ultimately included in this study, including 100 nonfunctional PanNENs and 85 insulinomas. Clinicopathologic features, serum lipid level and overall survival results were retrospectively analyzed using statistical methods. Results: In 185 PanNENs, 95 (51.4%) patients appear to have dyslipidemia. Patients with insulinoma had a lower proportion of abnormal HDL than those with nonfunctional PanNENs (10.6% vs 23%, P=0.026). The mean serum HDL levels of insulinomas were 0.131 mmol/L higher than the NF-PanNENs (1.306 ± 0.324 vs 1.175 ± 0.315, P=0.006). In multivariate logistic analysis, high levels of HDL are negatively correlated to tumor size (OR 0.233, 95% CI: 0.069-0.790, P=0.019), but HDL was not associated with pathological grade or metastasis. And a correlation has been found between hypercholesterolemia and the original location of the tumor (OR:0.224, 95%CI: 0.066-0.753, P =0.016). In addition, the outcome of the survival analysis revealed that dyslipidemia did not influence the prognosis of PanNENs patients (P>0.05). Conclusions: HDL was negatively correlated with the tumor size of PanNENs. The serum HDL level of insulinoma patients is higher than nonfunctional PanNENs.

Polyphenol oxidases regulate pollen development through modulating flavonoids homeostasis in tobacco.

Pollen development is critical in plant reproduction. Polyphenol oxidases (PPOs) genes encode defense-related enzymes, but the role of PPOs in pollen development remains largely unexplored. Here, we characterized NtPPO genes, and then investigated their function in pollen via creating NtPPO9/10 double knockout mutant (cas-1), overexpression 35S::NtPPO10 (cosp) line and RNAi lines against all NtPPOs in Nicotiana tabacum. NtPPOs were abundantly expressed in the anther and pollen (especially NtPPO9/10). The pollen germination, polarity ratio and fruit weights were significantly reduced in the NtPPO-RNAi and cosp lines, while they were normal in cas-1 likely due to compensation by other NtPPO isoforms. Comparisons of metabolites and transcripts between the pollen of WT and NtPPO-RNAi, or cosp showed that decreased enzymatic activity of NtPPOs led to hyper-accumulation of flavonoids. This accumulation might reduce the content of ROS. Ca2+ and actin levels also decreased in pollen of the transgenic lines.Thus, the NtPPOs regulate pollen germination through the flavonoid homeostasis and ROS signal pathway. This finding provides novel insights into the native physiological functions of PPOs in pollen during reproduction.

Prognostic role and predictors of lymph node involvement in pancreatic neuroendocrine tumors.

PURPOSE: To define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features. METHODS: This study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared. RESULTS: Forty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046-5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034-4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005-8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057-47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070-6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047-22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124-7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3-year DFS: 85.9 vs. 96.7%; p < 0.001; 5-year DFS: 65.1 vs. 93.9%; p < 0.001). CONCLUSION: LNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI.

The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis.

Objective: The objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS). Methods: We retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS. Results: Of the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification. Conclusion: CSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway.

BACKGROUND: Monocytes/macrophages play critical roles in inflammation and cardiac remodeling following myocardial infarction (MI). The cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses by activating α7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. We investigated the effect of α7nAChR on MI-induced monocyte/macrophage recruitment and polarization and its contribution to cardiac remodeling and dysfunction. METHODS: Adult male Sprague Dawley rats underwent coronary ligation and were intraperitoneally injected with the α7nAChR-selective agonist PNU282987 or the antagonist methyllycaconitine (MLA). RAW264.7 cells were stimulated with lipopolysaccharide (LPS) + interferon-gamma (IFN-γ) and treated with PNU282987, MLA, and S3I-201 (a STAT3 inhibitor). Cardiac function was evaluated by echocardiography. Masson's trichrome and immunofluorescence were used to detect cardiac fibrosis, myocardial capillary density, and M1/M2 macrophages. Western blotting was used to detect protein expression, and the proportion of monocytes was measured using flow cytometry. RESULTS: Activating the CAP with PNU282987 significantly improved cardiac function and reduced cardiac fibrosis and 28-day mortality after MI. On days 3 and 7 post-MI, PNU282987 reduced the percentage of peripheral CD172a + CD43low monocytes and the infiltration of M1 macrophages in the infarcted hearts, whereas it increased the recruitment of peripheral CD172a + CD43high monocytes and M2 macrophages. Conversely, MLA exerted the opposite effects. In vitro, PNU282987 inhibited M1 macrophage polarization and promoted M2 macrophage polarization in LPS + IFN-γ-stimulated RAW264.7 cells. These PNU282987-induced changes in LPS + IFN-γ-stimulated RAW264.7 cells were reversed by administering S3I-201. CONCLUSION: Activating α7nAChR inhibits the early recruitment of pro-inflammatory monocytes/macrophages during MI and improves cardiac function and remodeling. Our findings suggest a promising therapeutic target for regulating monocyte/macrophage phenotypes and promoting healing after MI.

Aberrant alteration of peripheral B lymphocyte subsets in hepatocellular carcinoma patients.

Although B lymphocytes are widely known to participate in the immune response, the conclusive roles of B lymphocyte subsets in the antitumor immune response have not yet been determined. Single-cell data from GEO datasets were first analyzed, and then a B cell flow cytometry panel was used to analyze the peripheral blood of 89 HCC patients and 33 healthy controls recruited to participate in our research. Patients with HCC had a higher frequency of B10 cells and a lower percentage of MZB cells than healthy controls. And the changes in B cell subsets might occur at an early stage. Moreover, the frequency of B10 cells decreased after surgery. Positively correlated with B10 cells, the elevated IL-10 level in HCC serum may be a new biomarker in HCC identification. For the first time, our results suggest that altered B cell subsets are associated with the development and prognosis of HCC. Increased B10 cell percentage and IL-10 in HCC patients suggest they might augment the development of liver tumors. Hence, B cell subsets and related cytokines may have predictive value in HCC patients and could be potential targets for immunotherapy in HCC.

Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

INTRODUCTION: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. METHODS: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. RESULTS: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. CONCLUSIONS: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.