Punicalagin Restricts Growth, Promotes Apoptosis, and Reduces Invasion in Human Gastric Cancer Cells.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Ca2LaTaO6:Bi3+/Mn4+ Phosphors with High Brightness Far-Red Emitting and Luminescence Enhancement for Plant Growth LED Lights and Temperature Sensor.

Herein, Bi3+/Mn4+ doped Ca2LaTaO6 phosphors with a double-perovskite structure were successfully synthesized with solid-state reaction at high temperature. The photoluminescence (PL) performances were investigated in detail. The blue radiation (∼465 nm) from the Bi3+ ion and the red radiation (∼686 nm) originating from the Mn4+ ion were obtained under 313 nm excitation. Especially, the pathway of energy transfer (Bi3+ → Mn4+) contributes to enhance the red emission intensity (Mn4+: ∼686 nm) in Ca2LaTaO6:Bi3+/Mn4+ system. The PL mechanism of Ca2LaTaO6:Bi3+/Mn4+ was analyzed through luminescence lifetimes and PL spectra. Moreover, the emitting bands of Ca2LaTaO6:Bi3+/Mn4+ were primarily matched with the absorbing bands of carotenoids and phytochrome PFR on behalf of plant growth, so the phosphors were suitable for the design of a plant growth light under near-ultraviolet to blue excitation. At last, the optical temperature dependent performances of the Ca2LaTaO6:Bi3+/Mn4+ were analyzed with luminescence intensity ratio technology. The sample has presented excellent temperature measuring relative sensitivity (SR = 2.106% K-1). The results illustrated that the Ca2LaTaO6:Bi3+/Mn4+ phosphor also can be used to develop an optical temperature sensor.

Enhanced TRPC3 transcription through AT1R/PKA/CREB signaling contributes to mitochondrial dysfunction in renal tubular epithelial cells in D-galactose-induced accelerated aging mice.

Aging-associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial dysfunction in renal tubular epithelial cells is a hallmark of senescence and leads to accelerated progression of renal disorders. Dysregulated calcium profiles in mitochondria contribute to aging-associated disorders, but the detailed mechanism of this process is not clear. In this study, modulation of the sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated renal glomerular sclerosis, tubular atrophy, and interstitial fibrosis in D-galactose (D-gal)-induced accelerated aging mice. Moreover, modulation of the Sirt1/AT1R pathway improved mitochondrial dysfunction induced by D-gal treatment. Transient receptor potential channel, subtype C, member 3 (TRPC3) upregulation mediated dysregulated cellular and mitochondrial calcium homeostasis during aging. Furthermore, knockdown or knockout (KO) of Trpc3 in mice ameliorated D-gal-induced mitochondrial reactive oxygen species production, membrane potential deterioration, and energy metabolism disorder. Mechanistically, activation of the AT1R/PKA pathway promoted CREB phosphorylation and nucleation of CRE2 binding to the Trpc3 promoter (-1659 to -1648 bp) to enhance transcription. Trpc3 KO significantly improved the renal disorder and cell senescence in D-gal-induced mice. Taken together, these results indicate that TRPC3 upregulation mediates age-related renal disorder and is associated with mitochondrial calcium overload and dysfunction. TRPC3 is a promising therapeutic target for aging-associated renal disorders.

Association of clinical characteristics and vaccines with risk of persistently viral clearance in patients infected with SARS-CoV-2 Omicron variant in Shanghai, China.

Importance: The global COVID-19 pandemic does not appear to end in the near future. Currently, limited data are available on the risk factors for delayed viral clearance in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Objective: This study aimed to investigate the association of clinical characteristics and vaccination with prolonged viral clearance. Methods: This retrospective cohort included 16,985 patients who had contracted the SARS-CoV-2 Omicron variant between April 5 and May 30, 2022, in Shanghai, China, and had mild or no symptoms. The patients were admitted to the quarantine venue at the Shanghai New International Expo Center. Results: Of the 16,985 participants, the occurrence of viral clearance was ≤8 and > 8 days in 11,009 (64.8 %) and 5976 (35.2 %) participants, respectively. Risk factors related to patients who remained persistently polymerase chain reaction (PCR)-positive were sex (Male, odds ratio [OR] 1.221, p < 0.001), older age (35-49, OR 1.389, p < 0.001; 50-64, OR 1.659, p < 0.001; ≥65, OR 2.139, p < 0.001), presence of symptoms (OR 1.093, p = 0.030), number of vaccinations (two doses, OR 0.753, p < 0.001; three doses, OR 0.797, p < 0.001; four doses, OR 0.543, p < 0.001), and cycle threshold (Ct) value for ORF1ab gene at diagnosis (25-35, OR 0.235, p < 0.001; >35, OR 0.079, p < 0.001). The lower rates of increase in Ct values were observed in the later viral shedding group than in the early viral shedding group for ORF1ab (ß = -0.791, p < 0.001) and N genes (ß = -0.825, p < 0.001). Conclusion: Prolonged SARS-CoV-2 RNA detection and higher viral concentrations were associated with factors such as male sex, older age, symptomatic status, and fewer doses of vaccination in patients admitted to Shanghai Makeshift Hospital between April 5 and May 30, 2022.

The biological age model for evaluating the degree of aging in centenarians.

BACKGROUND: Biological age (BA) has been used to assess individuals' aging conditions. However, few studies have evaluated BA models' applicability in centenarians. METHODS: Important organ function examinations were performed in 1798 cases of the longevity population (80∼115 years old) in Hainan, China. Eighty indicators were selected that responded to nutritional status, cardiovascular function, liver and kidney function, bone metabolic function, endocrine system, hematological system, and immune system. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and light gradient boosting machine (lightGBM) methods. A tenfold crossover validated the efficacy of models. RESULTS: A total of 1398 participants were enrolled, of whom centenarians accounted for 49.21%. Seven aging markers were obtained, including estimated glomerular filtration rate, albumin, pulse pressure, calf circumference, body surface area, fructosamine, and complement 4. Eight BA models were successfully constructed, namely MLR, PCA, KDM1, KDM2, RF, SVM, XGBoost and lightGBM, which had the worst R2 of 0.45 and the best R2 of 0.92. The best R2 for cross-validation was KDM2 (0.89), followed by PCA (0.62). CONCLUSION: In this study, we successfully applied eight methods, including traditional methods and machine learning, to construct models of biological age, and the performance varied among the models.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma.

Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient's prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

Punicalagin is cytotoxic to human colon cancer cells by modulating cell proliferation, apoptosis, and invasion.

Purpose: The purpose of this study was to explore the anticancer effect of punicalagin, an abundant bioactive tannin compound isolated from Punica granatum L., on three colon cancer cell lines, namely, HCT 116, HT-29, and LoVo.Research Design: Normal and colon cancer cells were treated with different concentrations of punicalagin for different periods. Data Collection and Analysis: Cell viability was measured with a CCK-8 assay. Programmed cell death and invasion were analyzed using an annexin V and cell death kit and a cell invasion analysis kit. The expression of active caspase-3, MMP-2, MMP-9, Snail, and Slug were measured by Western blot.Results: The results of the cell viability analysis showed that punicalagin was cytotoxic to colon cancer cells, but it was not to normal cells in a dose- and time-dependent manner. Additionally, punicalagin induced apoptosis in colon cancer cells (shown by the cumulative percentage of colorectal cancer cells in early and late apoptosis). It was found that caspase-3 activity increased following punicalagin treatment. Western blot results also showed that punicalagin increased the expression of activated caspase-3. In contrast, punicalagin inhibited the invasion of colon cancer cells. Further, treatment of colon cancer cells with punicalagin suppressed the expression of MMP-2, MMP-9, Snail, and Slug. Conclusions: These results showed that the activation of caspase-3 and the inhibition of MMP-2, MMP-9, Snail and Slug were involved in the effects of punicalagin on colon cancer cells.

LAMC2 is a potential prognostic biomarker for cholangiocarcinoma.

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-ßsignaling pathway' and 'platelet-derived growth factor receptor-ß signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.

Cartilage oligomeric matrix protein overexpression is an independent poor prognostic indicator in patients with intrahepatic cholangiocarcinoma.

Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker.

Elucidation of the mechanisms and molecular targets of KeChuanLiuWei-Mixture for treatment of severe asthma based on network pharmacology.

KeChuanLiuWei-Mixture (KCLW) is widely used as a Chinese medicine prescription to treat severe asthma. However, the underlying therapeutic mechanism of KCLW remains unclear. In this study, a network pharmacology method was used to identify the chemical constituents of KCLW by the TCMSP database and ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry. Differential expression identification, protein-protein interaction (PPI) network and functional enrichment analysis were used to screen key targets of KCLW for severe asthma. Our results confirmed that quercetin, luteolin, kaempferol, and wogonin are the most critical active ingredients in KCLW. Moreover, the 16 relevant severe asthma-related targets of KCLW were obtained by overlapping the PPI networks of the KCLW putative targets and severe asthma-related genes, among which the most important targets were IL-6, NOS2, VEGFA, CXCL2, and PLAT. Functionally, the 16-targets and their interacting differentially expressed genes were primarily related to biological functions and pathways related to immunity and inflammation, such as inflammatory response, T cell differentiation, Nrf2/HO-1 signaling pathway, TGF-ß/Smad signaling pathway, and NF-κB signaling pathway. KCLW inhibited inflammation in PDGF-BB-induced airway smooth muscle cells. In summary, this study demonstrates the active substance and potential therapeutic mechanism of KCLW in severe asthma, and offers a clinical direction for KCLW against severe asthma.

A Method for Detecting LDoS Attacks in SDWSN Based on Compressed Hilbert-Huang Transform and Convolutional Neural Networks.

Currently, Low-Rate Denial of Service (LDoS) attacks are one of the main threats faced by Software-Defined Wireless Sensor Networks (SDWSNs). This type of attack uses a lot of low-rate requests to occupy network resources and hard to detect. An efficient detection method has been proposed for LDoS attacks with the features of small signals. The non-smooth small signals generated by LDoS attacks are analyzed employing the time-frequency analysis method based on Hilbert-Huang Transform (HHT). In this paper, redundant and similar Intrinsic Mode Functions (IMFs) are removed from standard HHT to save computational resources and to eliminate modal mixing. The compressed HHT transformed one-dimensional dataflow features into two-dimensional temporal-spectral features, which are further input into a Convolutional Neural Network (CNN) to detect LDoS attacks. To evaluate the detection performance of the method, various LDoS attacks are simulated in the Network Simulator-3 (NS-3) experimental environment. The experimental results show that the method has 99.8% detection accuracy for complex and diverse LDoS attacks.

Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION: Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker.

Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an advanced stage, therefore, the clinical outcome is dismal. Dysregulation of urea cycle metabolic enzyme expression is found in different types of cancers. Nevertheless, a comprehensive evaluation of genes related to the urea cycle (i.e., GO:0000050) has not been conducted in IHCC. By performing a comparative analysis of gene expression profiles, we specifically examined genes associated with the urea cycle (GO:0000050) in a publicly accessible transcriptomic dataset (GSE26566). Interestingly, CPS1 was identified as the second most prominently down-regulated gene in this context. Tumor tissues of 182 IHCC patients who underwent curative-intent hepatectomy were enrolled. The expression level of CPS1 protein in our IHCC cohort was assessed by immunohistochemical study. Subsequent to that, statistical analyses were carried out to examine the expression of CPS1 in relation to various clinicopathological factors, as well as to assess its impact on survival outcomes. We noticed that lower immunoreactivity of CPS1 in IHCC was associated with tumor progression (pT status) with statistical significance (p = 0.003). CPS1 underexpression was not only negatively correlated to overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) in univariate analysis but also an independent prognosticator to forecast poorer clinical outcome for all prognostic indices (OS, DFS, LRFS and MeFs) in patients with IHCC (all p ≤ 0.001). These results support that CPS1 may play a crucial role in IHCC oncogenesis and tumor progression and serve as a novel prognostic factor and a potential diagnostic and theranostic biomarker.

Resveratrol triggers the ER stress-mediated intrinsic apoptosis of neuroblastoma cells coupled with suppression of Rho-dependent migration and consequently prolongs mouse survival.

Neuroblastoma, the most common childhood tumor, are highly malignant and fatal because neuroblastoma cells extremely defend against apoptotic targeting. Traditional treatments for neuroblastomas are usually ineffective and lead to serious side effects and poor prognoses. In this study, we investigated the molecular mechanisms of resveratrol-induced insults to neuroblastoma cells and survival extension of nude mice with neuroblastomas, especially in the endoplasmic reticular (ER) stress-intracellular reactive oxygen species (iROS) axis-mediated signals. Resveratrol specifically killed neuroblastoma cells mainly via apoptosis and autophagy rather than necrosis. As to the mechanisms, resveratrol time-dependently triggered productions of Grp78 protein and iROS in neuroblastoma cells. Attenuating the ER stress-iROS signaling axis significantly suppressed resveratrol-induced autophagy, DNA damage, and cell apoptosis. Successively, resveratrol decreased phosphorylation of retinoblastoma protein and induced cell cycle arrest at the S phase, translocation of Bak protein to mitochondria, a reduction in the mitochondrial membrane potential, cascade activation of caspases-9, -3, and -6, and DNA fragmentation. Moreover, weakening the ER stress-iROS axis concomitantly overcome resveratrol-induced decreases in translocation of Rho protein to membranes and succeeding cell migration. Interestingly, administration of resveratrol did not cause significant side effects but could protect the neuroblastoma-bearing nude mice from body weight loss and consequently extended the animal survival. In parallel, resveratrol elevated levels of Grp78 and then induced cell apoptosis in neuroblastoma tissues. This study has shown that resveratrol could kill neuroblastoma cells and extend survival of animals with neuroblastomas by triggering the ER stress-iROS-involved intrinsic apoptosis and suppression of Rho-dependent cell migration. Our results imply the potential of resveratrol as a drug candidate for chemotherapy of neuroblastoma patients.

Incidentally portal vein penetration during cannulation in endoscopic retrograde cholangiopancreatography: a case report.

Portal vein cannulation is a very rare complication of endoscopic retrograde cholangiopancreatography (ERCP). In most reported cases, the event was managed safely with immediate catheter, guidewire withdrawn and procedure termination. Here, we report an unusual case of portobiliary fistula created during ERCP. To our knowledge, this is the first report of such case managed with immediate surgical biliary exposure.

MPP7 is a potential prognostic marker and is associated with cancer metabolism and immune infiltration in clear cell renal cell carcinoma: a bioinformatics analysis based on the TCGA database.

Background: Metastasis is a major negative prognostic marker in clear cell renal cell carcinoma (ccRCC). Membrane palmitoylated proteins (MPPs) are a class of cell polarity-associated proteins that function in both cell-cell junction and adhesion. However, the relationship between MPP7 and the prognosis of ccRCC remains elusive. In this study, we aimed to investigate the associations between MPP7 expression with clinical prognosis of ccRCC using bioinformatics analyses. Methods: The messenger RNA (mRNA) and protein expression patterns of MPP7 in different cancer types were examined using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, with key clinical characteristics (TNM and pathological stages, pathological grade, survival status) included. A nomogram model using MPP7 expressions and other clinical factors was built to predict the survival probability. The Kaplan-Meier plotter and Cox regression were employed to investigate the clinical significance and prognostic value of MPP7 in ccRCC. MPP7 expression-associated signaling pathways with were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) tools. The Tumor Immune Estimation Resource (TIMER) database was used to investigate the correlation between MPP7 and the infiltration patterns of immune cells. Results: By analyzing TCGA-kidney renal clear cell carcinoma (TCGA-KIRC) and HPA databases, we found that MPP7 was differentially expressed in tumor tissues and adjacent normal tissues (P<0.001). The MPP7 expression patterns were associated with pathological stage (P<0.001), histological grade (P<0.01), and survival status (P<0.001). Using nomogram model, Cox regression and survival analysis, it showed that MPP7 expressions combined with key clinical factors could accurately predict the clinical prognosis. The promoter methylation patterns of MPP7 were correlated with the clinical factors of ccRCC patients. Furthermore, the KEGG and GO analyses demonstrated that MPP7 is associated with mitochondrial oxidative metabolism. MPP7 expression was associated with multiple types of immune cells and correlated with the enrichment of these cells. Conclusions: MPP7 is a critical gene links with ccRCC prognosis and is associated with tumor immune status and metabolism. MPP7 could become a potential biomarker and important therapeutic target for ccRCC patients.

Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate.

Extracellular vesicles (EVs) play a crucial role in regulating cell behavior by delivering their cargo to target cells. However, the mechanisms underlying EV-cell interactions are not well understood. Previous studies have shown that heparan sulfate (HS) on target cell surfaces can act as receptors for exosomes uptake, but the ligand for HS on EVs has not been identified. In this study, we isolated EVs from glioma cell lines and glioma patients and identified Annexin A2 (AnxA2) on EVs as a key HS-binding ligand and mediator of EV-cell interactions. Our findings suggest that HS plays a dual role in EV-cell interactions, where HS on EVs captures AnxA2, and on target cells, it acts as a receptor for AnxA2. Removal of HS from the EV surface inhibits EV-target cell interaction by releasing AnxA2. Furthermore, we found that AnxA2-mediated binding of EVs to vascular endothelial cells promotes angiogenesis, and that antibody against AnxA2 inhibited the ability of glioma-derived EVs to stimulate angiogenesis by reducing the uptake of EVs. Our study also suggests that the AnxA2-HS interaction may accelerate the glioma-derived EVs-mediated angiogenesis and that combining AnxA2 on glioma cells with HS on endothelial cells may effectively improve the prognosis evaluation of glioma patients.

Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. METHODS: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. RESULTS: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. CONCLUSIONS: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.

Efficacy of Lianhua Qingwen for children with SARS-CoV-2 Omicron infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Lianhua Qingwen Granules or Capsules (LHQW) has accumulated much research evidence in the fight against the coronavirus disease 2019 (COVID-19) epidemic. However, there are still few data on its efficacy and safety in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PURPOSE: To evaluate the efficacy and safety of LHQW in children with SARS-CoV-2 Omicron infection. METHODS: We conducted a single-center, propensity-score matched retrospective cohort study of children with SARS-CoV-2 Omicron infection in Shanghai New International Expo Center mobile cabin hospital between April 1st and June 1st, 2022. Eligible patients received either LHQW granules/capsules plus supportive care (LHQW group) or supportive care alone (control group). The primary outcome was the negative conversion time of nucleic acid. Secondary outcomes included the negative conversion rate of nucleic acid, the length of hospital stay, clinical disease progression, and cycle threshold [Ct] values for SARS-CoV-2 open reading frame [ORF1ab] or nucleocapsid [N] genes. RESULTS: Overall, 2808 patients were enrolled, and 346 patients in each group were included in the analysis. Among the propensity-score matched groups, LHQW treatment was associated with an accelerated negative conversion time of nucleic acid (median: 5 d vs. 6 d, Hazard ratio: 1.25, 95% CI: 1.08 - 1.46, Log-rank p < 0.001), a higher negative conversion rate of nucleic acid (Day 2 - 6: 2.9% vs. 0.6%, p = 0.036; 29.8% vs. 5.5%, p < 0.001; 42.5% vs. 24.3%, p < 0.001; 51.4% vs. 31.5%, p < 0.001; 63.3% vs. 55.2%, p = 0.030), shorter hospital stay (median: 10 d vs. 11 d, Hazard ratio: 1.50, 95% CI: 1.29 - 1.74, Log-rank p < 0.001), and lower rates of asymptomatic infection progressing to mild (37.9% vs. 46.5%, p = 0.021). CONCLUSION: Our study suggested that LHQW treatment was associated with faster clinical recovery in children with SARS-CoV-2 Omicron infection.