Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

HCC-1 Accelerates Atherosclerosis by Inducing Endothelial Cell and Macrophage Pyroptosis and Serves as an Early Diagnostic Biomarker.

BACKGROUND: HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 can predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis; however, the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis. METHODS: HCC-1 expression in serum, atherosclerotic plaques, and normal arterial tissue from patients with atherosclerosis and control group was assessed by ELISA, immunohistochemistry and confocal microscope, and bioinformatic analysis. The atherosclerotic model of HCC-1 overexpressing and control mice was generated by tail vein injection of adeno-associated virus serotype 9-HCC-1 on an ApoE-/- background. Cell adhesion, polarization, and pyroptosis were evaluated in vitro. The relationship between HCC-1 concentration in serum and atherosclerosis was analyzed in patients with atherosclerosis. RESULTS: HCC-1 expression was positively correlated with the occurrence and stable-unstable switch of atherosclerosis under bioinformatic analysis, which is further supported by the results of increased HCC-1 expression in atherosclerosis patients both in serum and atherosclerotic plaque. adeno-associated virus serotype 9-HCC-1 mice had higher levels of inflammatory factors, increased macrophage accumulation and pyroptotic rate in plaque, and decreased atherosclerotic plaque stability. In vitro, HCC-1 promoted monocyte adhesion and M1 polarization and induced inflammation and pyroptosis both in endothelial cells and macrophages. CONCLUSIONS: HCC-1 expression was increased in patients with atherosclerosis, and HCC-1 overexpression accelerated atherosclerotic burden via an enhancement in monocyte recruitment, M1 polarization, and pyroptosis both in endothelial cells and macrophages. Our findings suggested that HCC-1 may serve as an early biomarker for the diagnosis of atherosclerosis, with the capacity to reflect the degree of stenosis.

Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD. Methods: Hepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed. Results: Ileibacterium and Ruminococcaceae, both belonging to Firmicutes; Olsenella, Duncaniella and Paramuribaculum from Bacteroidota; and Bifidobacterium, Coriobacteriaceae_UCG_002 and Olsenella from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed. Conclusion: Through this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD.

Stimulator of Interferon Genes-Activated Biomimetic Dendritic Cell Nanovaccine as a Chemotherapeutic Booster to Enhance Systemic Fibrosarcoma Treatment.

Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.

Schisandrin A Attenuates Diabetic Nephropathy via EGFR/AKT/GSK3ß Signaling Pathway Based on Network Pharmacology and Experimental Validation.

Diabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein-protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3ß signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3ß pathway.

Gstp1 negatively regulates blood pressure in hypertensive rat via promoting APLNR ubiquitination degradation mediated by Nedd4.

Hypertension is a leading risk factor for disease burden worldwide. Vascular contraction and remodeling contribute to the development of hypertension. Glutathione S-transferase P1 (Gstp1) plays several critical roles in both normal and neoplastic cells. In this study, we investigated the effect of Gstp1 on hypertension as well as on vascular smooth muscle cell (VSMC) contraction and phenotypic switching. We identified the higher level of Gstp1 in arteries and VSMCs from hypertensive rats compared with normotensive rats for the first time. We then developed Adeno-associated virus 9 (AAV9) mediated Gstp1 down-regulation and overexpression in rats and measured rat blood pressure by using the tail-cuff and the carotid catheter method. We found that the blood pressure of spontaneously hypertensive rats (SHR) rose significantly with Gstp1 down-regulation and reduced apparently after Gstp1 overexpression. Similar results were obtained from the observations of 2-kidney-1-clip renovascular (2K1C) hypertensive rats. Gstp1 did not influence blood pressure of normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Further in vitro study indicated that Gstp1 knockdown in SHR-VSMCs promoted cell proliferation, migration, dedifferentiation and contraction, while Gstp1 overexpression showed opposite effects. Results from bioinformatic analysis showed that the Apelin/APLNR system was involved in the effect of Gstp1 on SHR-VSMCs. The rise in blood pressure of SHR induced by Gstp1 knockdown could be reversed by APLNR antagonist F13A. We further found that Gstp1 enhanced the association between APLNR and Nedd4 E3 ubiquitin ligases to induce APLNR ubiquitination degradation. Thus, in the present study, we discovered a novel anti-hypertensive role of Gstp1 in hypertensive rats and provided the experimental basis for designing an effective anti-hypertensive therapeutic strategy.

Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis.

The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.

Combined radiation and chemotherapy versus monotherapy for anaplastic thyroid cancer: A SEER retrospective analysis.

Background: The effect of combined radiation and chemotherapy (combination therapy) versus monotherapy on anaplastic thyroid carcinoma (ATC) has not yet been clear. Methods: We identified 516 ATC patients during 2010-2015 from the Surveillance, Epidemiology and End Results (SEER) database and evaluated their survival outcome using the Kaplan-Meier method, Cox regression analysis and propensity score matching (PSM) technique. Results: The median overall survival (OS) among the entire cohort was 3 months (95 % confidence interval [CI], 2.58-3.42 months), and the 6- and 12-month OS rates were 29 % (95 % CI, 25.01%-32.88 %) and 13 % (95 % CI, 10.60%-16.58 %), respectively. Multivariable analysis demonstrated that ATC patients not receiving radiotherapy or chemotherapy were unquestionably associated with worse OS (hazard ratio [HR] 3.000, 95 % CI, 2.390-3.764) and cancer-specific survival (CSS) (HR = 3.107, 95 % CI, 2.388-4.043), compared with those receiving combination therapy. However, combination therapy did not predict better prognosis compared with monotherapy (all P > 0.05). After PSM, the median OS and CSS were also not significantly improved in patients undergoing chemoradiotherapy versus chemotherapy alone (OS, P = 0.382; CSS, P = 0.420) or radiotherapy alone (OS, P = 0.065; CSS, P = 0.251). Conclusion: Combination therapy, compared to monotherapy, does not have the expected improvement in survival beyond the benefits achievable with each single-modality treatment, necessitating further prospective research to tailor its treatment management.

CTHRC1 serves as an indicator in biliary atresia for evaluating the stage of liver fibrosis and predicting prognosis.

BACKGROUND: Liver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE). AIMS: To explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA. METHODS: CTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA. RESULTS: CTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS). CONCLUSIONS: CTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.

A case study of Duchenne muscular dystrophy caused by Alu element insertion in DMD gene and analysis of its gray-hair symptoms.

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

People-centered primary care measures in health equity: a perspective of urban-rural comparison in Beijing, China.

Person-centered primary care measures (PCPCM) facilitate high-quality and culturally appropriate primary care. Access to PCPCM remains unequal between rural and urban areas, and the available evidence on rural PCPCM is still lacking. A cross-sectional survey was conducted with stratified sampling by regions, and four districts (Xicheng, Fengtai, Huairou, and Daxing) in Beijing were selected to test the performance of PCPCM in both urban and rural areas. Descriptive statistical methods were used to compare the urban-rural differences in the demographic characteristics of PCPCM. Correlation and regression analyses were performed to determine the associations between PCPCM in demographics and utilization of primary care. The PCPCM showed good reliability and validity in both urban and rural areas (P < .001), slightly lower in rural areas, but scores of rural PCPCM (R-PCPCM) in all items were lower than urban PCPCM (U-PCPCM). Patients in either the preferred urban or rural health centers all showed the highest PCPCM scores, with U-PCPCM= 3.31 for CHCs and R-PCPCM= 3.10 for RHCs, respectively. Patients in urban areas were more likely to receive higher-quality primary care than in rural areas (P < .001). Patients who preferred hospitals (ß = 2.61, P < .001) or CHCs (ß = 0.71, P = .003) as providers was a significant positive predictor of U-PCPCM but it was the preference for hospitals (ß = 2.95, P < .001) for R-PCPCM. Urban-rural differences existed in the performance of PCPCM, with rural areas typically more difficult to access better PCPCM. To promote health equity in rural areas, healthcare providers should strive to minimize urban-rural differences in the quality and utilization of primary care services as much as feasible.

Clinical application of serum CST4 combined with tumor markers in the diagnosis of digestive system malignant tumors.

The aim of the present study was to evaluate the diagnostic value of plasma human cystatin-S (CST4) in patients with digestive system malignant tumors. CST4 and tumor markers, such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, CA153 and CA724, were detected in blood samples from 100 patients with a digestive system malignant tumor and 100 patients with benign digestive system diseases. The tumor markers AFP, CEA, CA199, CA125, CA153 and CA724 were detected using an electrochemiluminescence immunoassay, and CST4 levels were detected using a human CST4 ELISA kit. The results demonstrated that the sensitivities of AFP and CA153 (both 5.00%) were significantly lower than that of CST4 (38.00%) in the diagnosis of digestive system malignancy (P<0.001), and CA724 (18.00%) was also less sensitive than CST4 (P<0.05). The sensitivities of CA199 (26.00%), CEA (31.00%) and CA125 (25.00%) were similar to that of CST4 (P>0.05). There was no significant difference in the CEA, CA125, CA724 and CST4 specificities (P>0.05), which were 91.00, 95.00, 94.00 and 83.00%, respectively. The specificities of AFP (99.00%), CA199 (98.00%) and CA153 (100.00%) were significantly higher than that of CST4 (P<0.01). By constructing a receiver operating characteristic curve and comparing the area under the curve as well as sensitivity, the findings of the present study demonstrated that combining CST4 with AFP, CEA, CA199, CA125, CA153 and CA724 can significantly enhance the diagnostic sensitivity for malignancies of the digestive system. However, the introduction of CST4 into the traditional diagnostic groups (CEA + AFP, CA199 + CA125 + CA153 + CA724 and AFP + CEA + CA199 + CA125 + CA153 + CA724) resulted in an increased sensitivity and loss of specificity, thereby not offering significant advantages in terms of comprehensive diagnostic efficiency compared with the traditional diagnostic groups. In conclusion, CST4 detection may be a promising diagnostic tool. Nonetheless, the potential false positive results in tumor diagnosis should be taken into consideration when developing new diagnostic groups involving CST4.

Community-dwelling older adults' perspectives on health risks: a qualitative study exploring anxieties, priorities, and expectations in ageing.

BACKGROUND: With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China inevitably experience anxieties surrounding health risks. This study aims to investigate how older adults perceive the health risks that come with getting older, explore the degree to which health risks affect older adults, and advocate for active engagement in practices for managing health risks. METHODS: Using purposive sampling, three districts of Beijing (Xicheng District, Fengtai District, and Daxing District, respectively) were selected for the research. Qualitative semi-structured and in-depth interviews were conducted with 70 community-dwelling older adults who participated in the study. Data were extracted and analyzed based on a thematic framework approach. RESULTS: Three main themes were identified: (i) the anxieties of older adults concerning health risks in ageing; (ii) the priorities of older adults for health risk management in ageing; (iii) the expectations of older adults for health risk management in ageing. The primary health concerns among older adults included disease incidence and function decline. It was found that basic health management emerged as a critical need for older adults to mitigate health risks. Moreover, it was observed that healthcare support for older adults from familial, institutional, and governmental levels exhibited varying degrees of inadequacy. CONCLUSIONS: The primary source of anxieties among older adults regarding health risks predominantly stems from a perceived sense of health deprivation. It is often compounded by persistent barriers to primary care of priorities in managing health risks among older adults. In addition, the expectations of older adults for health risk management emphasize the necessity for integrated care approaches. Therefore, further research should give priority to the prevention and management of health risks, aim to reduce anxieties, provide integrated care to meet the primary needs and expectations of older adults, and ultimately strive toward the overarching goal of promoting health and longevity.

Unraveling the impact of AXIN1 mutations on HCC development: Insights from CRISPR/Cas9 repaired AXIN1-mutant liver cancer cell lines.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with significant morbidity and mortality rates. AXIN1 is one of the top-mutated genes in HCC, but the mechanism by which AXIN1 mutations contribute to HCC development remains unclear. METHODS: In this study, we utilized CRISPR/Cas9 genome editing to repair AXIN1-truncated mutations in five HCC cell lines. RESULTS: For each cell line we successfully obtained 2-4 correctly repaired clones, which all show reduced ß-catenin signaling accompanied with reduced cell viability and colony formation. Although exposure of repaired clones to Wnt3A-conditioned medium restored ß-catenin signaling, it did not or only partially recover their growth characteristics, indicating the involvement of additional mechanisms. Through RNA-sequencing analysis, we explored the gene expression patterns associated with repaired AXIN1 clones. Except for some highly-responsive ß-catenin target genes, no consistent alteration in gene/pathway expression was observed. This observation also applies to the Notch and YAP/TAZ-Hippo signaling pathways, which have been associated with AXIN1-mutant HCCs previously. The AXIN1-repaired clones also cannot confirm a recent observation that AXIN1 is directly linked to YAP/TAZ protein stability and signaling. CONCLUSIONS: Our study provides insights into the effects of repairing AXIN1 mutations on ß-catenin signaling, cell viability, and colony formation in HCC cell lines. However, further investigations are necessary to understand the complex mechanisms underlying HCC development associated with AXIN1 mutations.

NB-TCM-CHM: Image dataset of the Chinese herbal medicine fruits and its application in classification through deep learning.

Chinese herbal medicine (CHM) is integral to a traditional Chinese medicine (TCM) system. Accurately identifying Chinese herbal medicine is crucial for quality control and prescription compounding verification. However, with many Chinese herbal medicines and some with similar appearances but different therapeutic effects, achieving precise identification is a challenging task. Traditional manual identification methods have certain limitations, including labor-intensive, inefficient. Deep learning techniques for Chinese herbal medicine identification can enhance accuracy, improve efficiency and lower coats. However, few high-quality Chinese herbal medicine datasets are currently available for deep learning applications. To alleviate this problem, this study constructed a dataset (Dataset 1) containing 3,384 images of 20 common Chinese herbal medicine fruits through web crawling. All images are annotated by TCM experts, making them suitable for training and testing Chinese herbal medicine identification methods. Furthermore, this study establishes another dataset (Dataset 2) of 400 images by taking pictures using smartphones to provide materials for the practical efficacy evaluation of Chinese herbal medicine identification methods. The two datasets form a Ningbo Traditional Chinese Medicine Chinese Herb Medicine (NB-TCM-CHM) Dataset. In Dataset 1 and Dataset 2, each type of Chinese medicine herb is stored in a separate folder, with the folder named after its name. The dataset can be used to develop Chinese herbal medicine identification algorithms based on deep learning and evaluate the performance of Chinese herbal medicine identification methods.

Clinical application of serum seven tumour-associated autoantibodies in patients with pulmonary nodules.

Background: The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice. Methods: We included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value. Results: The positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients (P < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients (P < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8-20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm (P < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions (P < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules (P < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules (P < 0.05). Conclusion: The low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.

Momentum-Resolved Electronic Structures and Strong Electronic Correlations in Graphene-like Nitride Superconductors.

Although transition-metal nitrides have been widely applied for several decades, experimental investigations of their high-resolution electronic band structures are rare due to the lack of high-quality single-crystalline samples. Here, we report on the first momentum-resolved electronic band structures of titanium nitride (TiN) films, which are remarkable nitride superconductors. The measurements of the crystal structures and electrical transport properties confirmed the high quality of these films. More importantly, from a combination of high-resolution angle-resolved photoelectron spectroscopy and first-principles calculations, the extracted Coulomb interaction strength of TiN films can be as large as 8.5 eV, whereas resonant photoemission spectroscopy yields a value of 6.26 eV. These large values of Coulomb interaction strength indicate that superconducting TiN is a strongly correlated system. Our results uncover the unexpected electronic correlations in transition-metal nitrides, potentially providing a perspective not only to understand their emergent quantum states but also to develop their applications in quantum devices.

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway.

Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1ß, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.

Formation mechanism, environmental sensitivity and functional characteristics of succinylated ovalbumin/ε-polylysine electrostatic complexes: The roles of succinylation modification and ε-polylysine combination.

Biocomplex materials formed by oppositely charged biopolymers (proteins) tend to be sensitive to environmental conditions and may lose part functional properties of original proteins, and one of the approaches to address these weaknesses is protein modification. This study established an electrostatic composite system using succinylated ovalbumin (SOVA) and ε-polylysine (ε-PL) and investigated the impact of varying degrees of succinylation and ε-PL addition on microstructure, environmental responsiveness and functional properties. Molecular docking illustrated that the most favorable binding conformation was that ε-PL binds to OVA groove, which was contributed by the multi­hydrogen bonding and hydrophobic interactions. Transmission electron microscopy observed that SOVA/ε-PL had a compact spherical structure with 100 nm. High-degree succinylation reduced complex sensitivity to heat, ionic strength, and pH changes. ε-PL improved the gel strength and antibacterial properties of SOVA. The study suggests possible uses of SOVA/ε-PL complex as multifunctional protein complex systems in the field of food additives.

Ultrasimple size encoded microfluidic chip for rapid simultaneous multiplex detection of DNA sequences.

Simultaneous multiplexed analysis can provide comprehensive information for disease diagnosis. However, the current multiplex methods rely on sophisticated barcode technology, which hinders its wider application. In this study, an ultrasimple size encoding method is proposed for multiplex detection using a wedge-shaped microfluidic chip. Driving by negative pressure, microparticles are naturally arranged in distinct stripes based on their sizes within the chip. This size encoding method demonstrates a high level of precision, allowing for accuracy in distinguishing 3-5 sizes of microparticles with a remarkable accuracy rate of up to 99%, even the microparticles with a size difference as small as 0.5 µm. The entire size encoding process is completed in less than 5 min, making it ultrasimple, reliable, and easy to operate. To evaluate the function of this size encoding microfluidic chip, three commonly co-infectious viruses' nucleic acid sequences (including complementary DNA sequences of HIV and HCV, and DNA sequence of HBV) are employed for multiplex detection. Results indicate that all three DNA sequences can be sensitively detected without any cross-interference. This size-encoding microfluidic chip-based multiplex detection method is simple, rapid, and high-resolution, its successful application in serum samples renders it highly promising for potential clinical promotion.