Search

Abstract There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Abstract Purpose This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). Methods We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle–Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. Results Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = − 17.73, 95%CI = − 25.65 to − 9.80, P

Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Abstract Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.

The challenge of understanding the interaction between trace elements and microbial life is critical for assessing environmental and ecological impacts. Nevertheless, cysteine (Cys), a low molecular weight thiol substance prevalent in the ecosystem, is able to influence the fate of certain trace elements, which increases the complexity of the interaction between trace elements and microorganisms. Therefore, we chose Cys, selenite and the model methanogenic archaeon Methanosarcina acetivorans C2A as research targets, and comprehensively explored the intricate role of Cys in modulating the biological effects of selenite on M. acetivorans C2A in terms of population growth, methane production and oxidative stress. Our results demonstrate that Cys significantly exacerbates the inhibitory effects of selenite on growth and methane production in M. acetivorans C2A. This increased toxicity is linked to heightened membrane permeability and oxidative stress, with a marked upregulation in reactive oxygen species and changes in NADPH levels. Transcriptomic analysis reveals alterations in genes associated with transmembrane transport and methanogenesis. Intriguingly, we also observed a potential interaction between selenite and phosphate transmembrane transporters, suggesting a novel pathway for selenite entry into cells. These findings highlight the complex interplay between trace elements and microbial processes, with significant implications for understanding environmental risks and developing remediation strategies.

Abstract Background: Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs. Methods: In this study, cation exchange chromatography was used to separate seven chromatographic components from Naja naja atra venom. Capillary electrophoresis was employed to detect that Ⅶ peak component containing a main protein Ⅶ-2, which could bind to ASIC1a. The analgesic effects of Ⅶ-2 protein were determined using hot plate methods, and ASIC1a expression in spinal cord tissue from rats with inflammatory pain was detected using western blot. Results: The purified Ⅶ-2 protein named Naja naja atra venom-Ⅶ-2 (NNAV-Ⅶ-2) was obtained by Sephadex G-50 gel filtration, which exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 6.7 kD. Remarkably, the NNAV-Ⅶ-2 protein demonstrated a significant analgesic effect and downregulated ASIC1a expression in the spinal cord tissue of rats with inflammatory pain. Conclusions: The analgesic mechanism of the NNAV-Ⅶ-2 protein may be associated with its binding to ASIC1a, consequently downregulating ASIC1a expression in neural tissues.

Abstract Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2–DSAD1 and DSR2–DSAD1–NAD+, as well as active DSR2–tube and DSR2–tube–NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.

AimThe aim of this study was to develop a validated nomogram to predict the risk of postoperative complications in colorectal cancer (CRC) patients by analyzing the factors that contribute to these complications.MethodsWe retrospectively collected clinical information on patients who underwent CRC surgery at a single clinical center from January 2021 to December 2021. Univariate and multivariate logistic regression analysis to identify independent risk factors for postoperative complications and to develop a predictive model. A receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) to assess the predicted probability. Calibration curve was drawn to compare the predicted probability of the nomogram with the actual probability, and decision curve analysis (DCA) was employed to evaluate the clinical utility of the nomogram.ResultsA total of 190 CRC patients were included in this study. We retrospectively collected baseline information, clinical information, surgical information, and nutrition-related indicators for all patients. Through multivariate logistic regression analysis, preoperative albumin (p = 0.041, OR = 0.906, 95% CI = 0.824–0.996), surgical time (p = 0.009, OR = 1.006, 95% CI = 1.001–1.010), waistline (p = 0.049, OR = 1.011, 95% CI = 1.002–1.020) and phase angle (PA) (p = 0.022, OR = 0.615, 95% CI = 0.405–0.933) were identified as independent risk factors for postoperative complications in CRC, and a nomogram prediction model was established using the above four variables. The AUC of 0.706 for the ROC plot and the high agreement between predicted and actual probabilities in the calibration curves suggested that the prediction model has good predictive power. The DCA also confirmed the good clinical performance of the nomogram.ConclusionThis study developed a nomogram to predict the risk of postoperative complications in CRC patients, providing surgeons with a reliable reference to personalized patient management in the perioperative period and preoperative nutritional interventions.

Background and ObjectiveChronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment.MethodTraditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient’s symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom–botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.Results5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway.ConclusionBased on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

Abstract Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems’ complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Abstract Background Ambient fine particulate matter (PM2.5) is considered a plausible contributor to the onset of chronic obstructive pulmonary disease (COPD). Mechanistic studies are needed to augment the causality of epidemiologic findings. In this study, we aimed to test the hypothesis that repeated exposure to diesel exhaust particles (DEP), a model PM2.5, causes COPD-like pathophysiologic alterations, consequently leading to the development of specific disease phenotypes. Sprague Dawley rats, representing healthy lungs, were randomly assigned to inhale filtered clean air or DEP at a steady-state concentration of 1.03 mg/m3 (mass concentration), 4 h per day, consecutively for 2, 4, and 8 weeks, respectively. Pulmonary inflammation, morphologies and function were examined. Results Black carbon (a component of DEP) loading in bronchoalveolar lavage macrophages demonstrated a dose-dependent increase in rats following DEP exposures of different durations, indicating that DEP deposited and accumulated in the peripheral lung. Total wall areas (WAt) of small airways, but not of large airways, were significantly increased following DEP exposures, compared to those following filtered air exposures. Consistently, the expression of α-smooth muscle actin (α-SMA) in peripheral lung was elevated following DEP exposures. Fibrosis areas surrounding the small airways and content of hydroxyproline in lung tissue increased significantly following 4-week and 8-week DEP exposure as compared to the filtered air controls. In addition, goblet cell hyperplasia and mucus hypersecretions were evident in small airways following 4-week and 8-week DEP exposures. Lung resistance and total lung capacity were significantly increased following DEP exposures. Serum levels of two oxidative stress biomarkers (MDA and 8-OHdG) were significantly increased. A dramatical recruitment of eosinophils (14.0-fold increase over the control) and macrophages (3.2-fold increase) to the submucosa area of small airways was observed following DEP exposures. Conclusions DEP exposures over the courses of 2 to 8 weeks induced COPD-like pathophysiology in rats, with characteristic small airway remodeling, mucus hypersecretion, and eosinophilic inflammation. The results provide insights on the pathophysiologic mechanisms by which PM2.5 exposures cause COPD especially the eosinophilic phenotype.

Abstract Background and Aim The aim of this study was to assess the quality and content of videos on Douyin and TikTok for their educational role on early screening of rectal cancer (RC). Methods We conducted a search for videos related to RC on the Douyin and TikTok applications on 20 April 2023. The search was conducted in Chinese on Douyin and in English and Japanese on TikTok. A sample of the first 100 videos recommended by the software was selected for each language group. The content of the videos was evaluated using a content scorecard, while the quality of the videos was assessed using DISCERN. Subsequently, we conducted two partial correlations: one between the DISCERN score and the number of likes, and another between the video content score and the number of likes. Results This study encompassed a total of 89 Chinese, 54 English, and 51 Japanese videos. After selection, 78 Chinese, 38 English, and 25 Japanese videos were identified to contain content related to early screening for RC, prompting further quality assessment. Notably, videos in the Chinese language showed the highest DISCERN score (P 0.05). Conclusion In terms of quality score and content score, the Chinese videos on Douyin show superiority over the English and Japanese videos on TikTok. However, there is potential for improving the overall appeal of the Chinese videos.

ABSTRACTObjectives Chromosome segregation 1-like (CSE1L) is abundant and strongly expressed in solid tumors. However, the expression and role of CSE1L in chronic myeloid leukemia(CML) remain largely unknown.Materials and methods The relative expression levels of CSE1L in bone marrow granulocytes from patients with primary CML and non-hematologic controls were measured by flow cytometry. Cell counting kit-8 analysis, DNA Content Quantitation Assay, and Annexin V-PE/7-AAD staining were applied to assess the effects of CSE1L knockdown on cell proliferation, cell cycle progression, and apoptosis.Results Elevated expression of CSE1L was detected in bone marrow granulocytes of patients with primary CML. In the CML cell line K562 cells, CSE1L knockdown impaired cell proliferation blocked the cell cycle shift from G0/G1 phase to the S phase, and promoted apoptosis. Knockdown of CSE1L reduced Bcl-2 protein expression and increased Bax protein expression. Meanwhile, knockdown of CSE1L enhanced the expression of phospho-AMPK protein and decreased the expression of phospho-mTOR protein. The expression of total AMPK and mTOR proteins was not affected. In addition, CSE1L expression levels were decreased in imatinib-treated K562 cells.Conclusions CSE1L plays a pivotal role in K562 cell survival and growth. These functions may be partially dependent on the AMPK/mTOR signaling pathway to achieve. In addition, CSE1L may have had a future impact on the treatment of CML patients.

Brevetoxins (PbTxs) are very potent marine neurotoxins that can cause an illness clinically described as neurologic shellfish poisoning (NSP). These toxins are cyclic polyether in chemistry and have increased their geographical distribution in the past 2 decades. However, the ethical problems as well as technical difficulties associated with currently employed analysis methods for marine toxins have spurred the quest for suitable alternatives to be applied in a regulatory monitoring regime. In this work, we reported the first instance of concurrent aptamer selection of Brevetoxin-1 (PbTx-1) and Brevetoxin-2 (PbTx-2) and constructed a biolayer interferometry (BLI) biosensor utilizing PbTx-1 aptamer as a specific recognition element. Through an in vitro selection process, we have, for the first time, successfully selected DNA aptamers with high affinity and specificity to PbTx-1 and PbTx-2 from a vast pool of random sequences. Among the selected aptamers, aptamer A5 exhibited the strongest binding affinity to PbTx-1, with an equilibrium dissociation constant (KD) of 2.56 μM. Subsequently, we optimized aptamer A5 by truncation to obtain the core sequence (A5-S3). Further refinement was achieved through mutations based on the predictions of a QGRS mapper, resulting in aptamer A5-S3G, which showed a significant increase in the KD value by approximately 100-fold. Utilizing aptamer A5-S3G, we fabricated a label-free, real-time optical BLI aptasensor for the detection of PbTx-1. This aptasensor displayed a broad detection range from 100 nM to 4000 nM PbTx-1, with a linear range between 100 nM and 2000 nM, and a limit of detection (LOD) as low as 4.5 nM. Importantly, the aptasensor showed no cross-reactivity to PbTx-2 or other marine toxins, indicating a high level of specificity for PbTx-1. Moreover, the aptasensor exhibited excellent reproducibility and stability when applied for the detection of PbTx-1 in spiked shellfish samples. We strongly believe that this innovative aptasensor offers a promising alternative to traditional immunological methods for the specific and reliable detection of PbTx-1.

Abstract The purpose of this study was to investigate whether patients with colorectal cancer (CRC) combined with hyperuricemia remitted 1 year after CRC surgery. CRC patients combined with hyperuricemia who underwent radical surgery were included from a single clinical center from Jan 2016 to Dec 2021. Baseline characteristics was compared between the remission group and the non-remission group. Multivariate logistic regression was used to find the possible predictive factors of hyperuricemia remission. A total of 91 patients were included for data analysis, retrospectively. There were 34 (37.4%) patients in the remission group and 57 (62.6%) patients in the non-remission group. The mean preoperative weight and body mass index (BMI) were 61.2 ± 10.7 (kg) and 24.1 ± 3.3 (kg/m2). 21 (23.1%) patients had a history of drinking. We found that the weight and BMI were not significantly different before and 1 year after CRC surgery (P > 0.05). In contrast, uric acid values were significantly decreased (P 0.05). According to multivariate logistic regression, we found that the history of drinking was a predictive factor of hyperuricemia remission (OR = 0.046, 95% CI 0.005–0.475, P = 0.010). CRC patients with hyperuricemia had a 37.4% remission from hyperuricemia 1 year after CRC surgery. Tumor location, tumor stage, and tumor size did not predict the remission of hyperuricemia. Notably, the history of drinking was a predictive factor of hyperuricemia remission.

Abstract Colon cancer is a common malignancy of the digestive tract. Colon cancer stem-like cells (CCSCs) are theoretically one of the key drivers of the initiation, relapse, metastasis, and chemo-resistance of colon tumors. Piezo1 is a mechanosensitive cationic channel protein involved in cancer progression. However, little is known regarding the possible role of Piezo1 in maintaining the stemness of CCSCs. In this study, we found that Piezo1 was highly expressed in CD133+/CD44+ colon cancer tissues, and the Piezo1high/CD133+CD44+ population was associated with the clinical stage. Furthermore, CCSCs isolated from colon cell lines expressed higher Piezo1 levels compared to the non-CCSCs, and Piezo1 knockdown inhibited their tumorigenicity and self-renewal capacity. Mechanistically, Piezo1 maintained the stemness of CCSCs through Ca2+/NFAT1 signaling, and knocking down Piezo1 promoted degradation of NFAT1. Taken together, Piezo1 is involved in the stage of colon cancer and is a promising therapeutic target.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.

Abstract Purpose The aim of this study was to analyze the effect of preoperative bicarbonate and lactate levels (LL) on the short-term outcomes and prognosis in elderly (≥ 65 years) patients with colorectal cancer (CRC). Methods We collected the information of CRC patients from Jan 2011 to Jan 2020 in a single clinical center. According to the results of preoperative blood gas analysis, we divided patients into the higher/lower bicarbonate group and the higher/lower lactate group, and compared their baseline information, surgery-related information, overall survival (OS) and disease-free survival (DFS). Results A total of 1473 patients were included in this study. Comparing the clinical data of the higher/lower bicarbonate group and the higher/lower lactate group, the lower group were older (p

Abstract Background The advanced lung cancer inflammation index (ALI) is a comprehensive assessment indicator that can reflect inflammation and nutrition conditions. However, there are some controversies about whether ALI is an independent prognostic factor for gastrointestinal cancer patients undergoing surgical resection. Thus, we aimed to clarify its prognostic value and explore the potential mechanisms. Methods Four databases including PubMed, Embase, the Cochrane Library, and CNKI were used for searching eligible studies from inception to June 28, 2022. All gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EC), liver cancer, cholangiocarcinoma, and pancreatic cancer were enrolled for analysis. We focused on prognosis most in the current meta-analysis. Survival indicators, including overall survival (OS), disease-free survival (DFS), and cancer-special survival (CSS) were compared between the high ALI group and the low ALI group. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was submitted as a supplementary document. Results We finally included fourteen studies involving 5091 patients in this meta-analysis. After pooling the hazard ratios (HRs) and 95% confidence intervals (CIs), ALI was found to be an independent prognostic factor for both OS (HR = 2.09, I2 = 92%, 95% CI = 1.53 to 2.85, P

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2–7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1–7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

Purpose The purpose of this study was to investigate the effect of laparoscopic left colectomy (LLC) and laparoscopic sigmoidectomy (LSD) on short-term outcomes and prognosis of sigmoid colon cancer (SCC) patients using propensity score matching (PSM). Methods In this retrospective study, the SCC patients who underwent LLC or LSD surgery were collected from a single clinical center from Jan 2011 to Dec 2019. Short-term outcomes and prognosis were compared between patients who received LSD surgery and LLC surgery. Results A total of 356 patients were included in this study. After 1:1 PSM analysis, there were 50 patients who underwent LLC surgery and 50 patients who underwent LSD surgery left in this study. No significant difference was found in baseline characteristics after PSM ( P > .05). In comparison with the LLC surgery group, the LSD surgery group had shorter operation time ( P = .003) after PSM. Moreover, the surgical procedure was not an independent predictor for overall survival (OS) ( P = .918, 95% CI = .333–2.688) and disease-free survival DFS ( P = .730, 95% CI = .335–2.150), but age (OS: P = .009, 95% CI = 1.010–1.075; DFS: P = .014, 95% CI = 1.007–1.061) and tumor stage (OS: P = .004, 95% CI = 1.302–3.844; DFS: P < .01, 95% CI = 1.572–4.171) were the independent risk factors for OS and DFS in SCC patients. Conclusion There was no significant difference between the two surgical procedures for prognosis of SCC patients. However, the possible reasons for changing the surgical procedures should be cautious by surgeons.

The development of autonomous undersea vehicle recovery technology is the main approach to solve problems pertaining to energy and information transmission and to enhance the underwater detection and concealment capabilities of unmanned systems. In this study, an underwater visual guidance scheme is designed for recovery with funnel-shaped docking stations in an actual environment. Additionally, an improved detect-by-tracking algorithm based on a convolutional neural network(CNN) is proposed. First, the CNN is trained using a docking station dataset to detect the target. Next, the improved tracking algorithm is combined with the position and attitude spatial information to achieve robust tracking. Finally, based on an improved PnP-P3P position and attitude estimation framework, the problem of insufficient observable beacons under a large offset is solved, and the underwater visual guidance workspace is effectively expanded. The beacon array design and algorithm are validated via workspace simulation, and relevant effective workspace indexes are proposed. An optical guidance experiment is performed in a pool, and acousto–optic joint guidance is performed based on an ultrashort baseline in an actual lake test. The feasibility of the proposed framework for engineering is confirmed by the results obtained.

The authors report several high-resolution functional snapshots of type III-E nuclease-protease Craspase complexes, revealing the mechanisms underlying target RNA cleavage and non-self RNA activated protease activities; and highlighting the potentials for the development of RNA-guided nuclease-protease Craspase-based tools for biotechnological applications.

Abstract Background The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA. Methods We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR. Results HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p

Studies on the preparation, structures, and properties of heterometallic complexes are currently of great interest because of their emergent synergistic properties. Although both rare earth and aluminum oxo clusters have been developed, only a few heterometallic compounds combine the two clusters. In this study, using “ligand-controlled partial hydrolysis”, we synthesize three hat-shaped cationic Al9Ln7 (Ln = Ce, Pr, Nd) clusters comprising tetrameric cubane units. Their unique vertex-to-edge-sharing arrangements have not been reported in either rare earth or aluminum oxo clusters. Apart from single-crystal X-ray diffraction, these compounds were characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, thermogravimetric analysis, and energy dispersive spectroscopy. Al9Ln7 clusters could serve as efficient catalysts for aldol condensation reactions between acetone and p-nitrobenzaldehyde under mild conditions, with an excellent yield of 86% by AlOC-129Ce.

Abstract Background Whether hypokalemia can affect the short-term outcomes of CRC patients after radical surgery remains unclear. The purpose of this study was to investigate the impact of preoperative hypokalemia on the short-term outcomes for colorectal cancer (CRC) patients who underwent radical CRC surgery using propensity score matching (PSM). Methods We retrospectively enrolled consecutive CRC patients from Jan 2011 to Dec 2021 in a single-center hospital. Hypokalemia was defined as a serum potassium concentration 0.05). Regarding short-term outcomes, the hypokalemia group had a longer hospital stay (p = 0.028), a higher proportion of overall complications (p = 0.048) and a higher incidence of postoperative pneumonia (p = 0.008) after PSM. Moreover, hypokalemia (p = 0.036, OR = 1.291, 95% CI = 1.017–1.639) was an independent risk factor for overall complications. Conclusion Preoperative hypokalemia could increase complications after CRC surgery and prolong the hospital stay. Moreover, preoperative hypokalemia was an independent risk factor for overall complications.

Abstract Purpose The purpose of the current study was to compare the outcomes of temporary stoma through the specimen extraction site (SSES) and stoma through a new site (SNS) after laparoscopic low anterior resection. Methods The rectal cancer patients who underwent laparoscopic low anterior resection plus temporary ileostomy were recruited in a single clinical database from Jun 2013 to Jun 2020. The SSES group and the SNS group were compared using propensity score matching (PSM) analysis. Results A total of 257 rectal cancer patients were included in this study, there were 162 patients in the SSES group and 95 patients in the SNS group. After 1:1 ratio PSM, there was no difference in baseline information (p > 0.05). The SSES group had smaller intraoperative blood loss (p = 0.016 0.05). In the multivariate analysis, longer operation time was an independent factor (p = 0.019

In this paper, a three-dimensional faster than real-time heat transfer model is presented for the continuous casting process. The model features a high computational capability required for real-time prediction, optimization, and control of the casting process. The computational model is implemented with a multi-level acceleration method on GPUs to ultimately shrink the computational time cost. This acceleration method helps to build a proper mapping from numerical models to GPU hardware features and provides two acceleration strategies with slight accuracy loss. With the multi-level acceleration method, a 117× speedup with a max 1.74% relative error compared to a 14-threaded CPU implementation is achieved. Moreover, the accuracy of the model has been verified with the Stefan problem and validated with industry measurement. The relative computational time, which is required to be less than 1 in real-time simulations and significantly far less than 1 in dynamic optimization of the casting process, is adopted to evaluate the real-time ability of the model. The proposed model achieves a relative computational time between 0.0003 for a coarse mesh and 0.015 for a very fine mesh. Our demonstrated high-performance modeling tool herein is envisioned to dominate among the applications of advanced process control and optimization in continuous casting.

Abstract Purpose The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM). Methods Patients who underwent primary radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group. Results A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p

PurposeThe aim of this study was to evaluate the effect of carbon nanoparticles staining (CNS) on colorectal cancer (CRC) surgery, lymph node tracing and postoperative complications using propensity score matching (PSM).MethodPatients who were diagnosed with CRC and underwent surgery were retrospectively collected from a single clinical center from Jan 2011 to Dec 2021. Baseline characteristics, surgical information and postoperative information were compared between the CNS group and the non-CNS group. PSM was used to eliminate bias.ResultsA total of 6,886 patients were enrolled for retrospective analysis. There were 2,078 (30.2%) patients in the CNS group and 4,808 (69.8%) patients in the non-CNS group. After using 1: 1 ratio PSM to eliminate bias, there were 2,045 patients left in each group. Meanwhile, all of their baseline characteristics were well matched and there was no statistical significance between the two groups (P > 0.05). In terms of surgical information and short-term outcomes, the CNS group had less intraoperative blood loss (P 0.05).ConclusionPreoperative CNS could help the surgeons detect more lymph nodes, thus better determining the patient's N stage. Furthermore, it could reduce intraoperative blood loss and reduce the hospital stay.

Abstract Purpose The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM). Methods This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65–79 years old). Results A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p

Abstract Background Online teaching has become increasingly common in higher education of the post-pandemic era. While a traditional face-to-face lecture or offline teaching remains very important and necessary for students to learn the medical knowledge systematically, guided by the BOPPPS teaching model, combination of online and offline learning approaches has become an unavoidable trend for maximizing teaching efficiency. However, in physiological education, the effectiveness of combined online teaching and offline teaching models remains poorly assessed. The present study aims at providing an assessment to the hybrid teaching model. Methods The study was performed among undergraduate medical students of Class 2017 ~ 2019 in the Physiology course in Harbin Medical University during 2018-2020. Based on established offline teaching model with BOPPPS components in 2018, we incorporated online teaching contents into it to form a hybrid BOPPPS teaching model (HBOPPPS, in brief), preliminarily in 2019 and completely in 2020. HBOPPPS effectiveness was assessed through comparing the final examination scores of both objective (multi-choice and single answer questions) and subjective (short and long essays) questions between classes taught with different modalities. Results The final examination score of students in Class 2019 (83.9 ± 0.5) who were taught with the HBOPPPS was significantly higher than that in Class 2017 (81.1 ± 0.6) taught with offline BOPPPS and in Class 2018 (82.0 ± 0.5) taught with immature HBOPPPS. The difference mainly attributed to the increase in average subjective scores (41.6 ± 0.3 in Class 2019, 41.4 ± 0.3 in Class 2018, and 38.2 ± 0.4 in Class 2017). In the questionnaire about the HBOPPPS among students in Class 2019, 86.2% responded positively and 79.4% perceived improvement in their learning ability. In addition, 73.5% of the students appreciated the reproducibility of learning content and 54.2% valued the flexibility of HBOPPPS. Lastly, 61.7% of the students preferred the HBOPPPS relative to BOPPPS in future learning. Conclusions HBOPPPS is likely a more effective teaching model and useful for enhancing effectiveness of Physiology teaching. This is attributable to the reproducibility and flexibility as well as the increased learning initiatives.

The aim of this study was to investigate the impact of liver cirrhosis (LC) on postoperative complications and long-term outcomes in patients who underwent cardiac surgery. Three databases, including PubMed, Embase, and the Cochrane Library, were searched on July 24, 2022. A total of 1,535,129 patients were enrolled in the seven included studies for analysis. According to our analysis, LC was a risk factor for postoperative overall complications (OR = 1.48, 95% CI = 1.21 to 1.81, I2 = 90.35%, P = 0.00 < 0.1). For various complications, more patients developed pulmonary (OR = 1.86, 95% CI = 1.21 to 2.87, I2 = 90.79%, P = 0.00 < 0.1), gastrointestinal (OR = 2.03, 95% CI = 1.32 to 3.11, I2 = 0.00%, P = 0.00 < 0.05), renal (OR = 2.20, 95% CI = 1.41 to 3.45, I2 = 91.60%, P = 0.00 < 0.1), neurological (OR = 1.14, 95% CI = 1.03 to 1.26, I2 = 7.35%, P = 0.01 < 0.05), and infectious (OR = 2.02, 95% CI = 1.17 to 3.50, I2 = 92.37%, P = 0.01 < 0.1) complications after surgery in the LC group. As for cardiovascular (OR = 1.07, 95% CI = 0.85 to 1.35, I2 = 75.23%, P = 0.58 > 0.1) complications, there was no statistical significance between the 2 groups. As for long-term outcomes, we found that in-hospital death (OR = 2.53, 95% CI = 1.86 to 3.20, I2 = 44.58%, P = 0.00 < 0.05) and death (OR = 3.31, 95% CI = 1.54 to 5.07, I2 = 93.81%, P = 0.00 < 0.1) in the LC group were higher than the non-LC group. LC was a risk factor for cardiac surgery. Patients with LC who would undergo cardiac surgery should be fully assessed for the risks of cardiac surgery. Similarly, the surgeon should assess the patient’s liver function before surgery.

Eight new scalarane sesterterpenes, phyllofenones F–M (1–8), together with two known analogues, carteriofenones B and A (9–10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 μg/mL and 8 μg/mL, respectively. Compounds 1–10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 μM.

Abstract Purpose The purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a propensity score matching (PSM) analysis. Methods We retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group. Results A total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p

Asymmetric catalysis has continued to enable the preparation of optically active natural products over the past decade. This minireview summarizes progress in the catalytic enantioselective total synthesis of complex monoterpenoid indole alkaloids covering the reports from 2019 to June 2021. In particular, generation of the key chiral stereogenic centers with metal catalysts and organocatalysts has been highlighted, showcasing the power of asymmetric catalysis protocols in accessing complex molecular architectures.

Abstract Current methods used for diagnosis of acute infection of pathogens rely on detection of nucleic acids, antigens, or certain classes of antibodies such as IgM. Here we report a virus enzyme assay as an alternative to these methods for detection of acute viral infection. In this method, we used a luciferin derivative as the substrate for detection of the enzyme activity of influenza viral neuraminidase as a means for diagnosis of influenza. The resulting commercial test, the qFLU Dx Test, uses a different supply chain that does not compete with those for the current tests. The assay reagents were formulated as a master mix that accommodated both the neuraminidase and luciferase reactions, thereby enabling rapid and prolonged production of stable light signal in the presence of influenza virus in the sample. The assay was evaluated using depository throat swab specimens. As expected, the assay exhibited similar detection rates for all influenza types and subtypes except for A(H7N9), which exhibited lower detection rate due to lower viral titer in the specimens. When throat swab specimens were diluted with the sample buffer of the test kit and tested with the qFLU Dx Test. The sensitivity and specificity were 82.41% (95% confidence interval: 79.66–85.84%) and 95.39% (95% confidence interval: 94.32–96.46%), respectively, for these diluted specimens in comparison to a real-time polymerase chain reaction assay. The uniqueness of the qFLU Dx Test as an enzymatic assay makes it highly complementary with currently available methods.

ABSTRACT Transcriptional factors (TFs) and their regulons make up the gene regulatory networks. Here, we developed a method based on TF-directed activation-induced cytidine deaminase (AID) mutagenesis in combination with genome sequencing, called AIDmut-Seq, to detect TF targets on the genome. AIDmut-Seq involves only three simple steps, including the expression of the AID-TF fusion protein, whole-genome sequencing, and single nucleotide polymorphism (SNP) profiling, making it easy for junior and interdisciplinary researchers to use. Using AIDmut-Seq for the major quorum sensing regulator LasR in Pseudomonas aeruginosa, we confirmed that a few TF-guided C-T (or G-A) conversions occurred near their binding boxes on the genome, and a number of previously characterized and uncharacterized LasR-binding sites were detected. Further verification of AIDmut-Seq using various transcriptional regulators demonstrated its high efficiency for most transcriptional activators (FleQ, ErdR, GacA, ExsA). We confirmed the binding of LasR, FleQ, and ErdR to 100%, 50%, and 86% of their newly identified promoters by using in vitro protein-DNA binding assay. And real-time RT-PCR data validated the intracellular activity of these TFs to regulate the transcription of those newly found target promoters. However, AIDmut-Seq exhibited low efficiency for some small transcriptional repressors such as RsaL and AmrZ, with possible reasons involving fusion-induced TF dysfunction as well as low transcription rates of target promoters. Although there are false-positive and false-negative results in the AIDmut-Seq data, preliminary results have demonstrated the value of AIDmut-Seq to act as a complementary tool for existing methods. IMPORTANCE Protein-DNA interactions (PDI) play a central role in gene regulatory networks (GRNs). However, current techniques for studying genome-wide PDI usually involve complex experimental procedures, which prevent their broad use by scientific researchers. In this study, we provide a in vivo method called AIDmut-Seq. AIDmut-Seq involves only three simple steps that are easy to operate for researchers with basic skills in molecular biology. The efficiency of AIDmut-Seq was tested and confirmed using multiple transcription factors in Pseudomonas aeruginosa. Although there are still some defects regarding false-positive and false-negative results, AIDmut-Seq will be a good choice in the early stage of PDI study.

Purpose. The current study was designed to investigate the impact of blood urea nitrogen (BUN), serum uric acid (UA), and cystatin (CysC) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients undergoing radical surgery. Methods. CRC patients who underwent radical resection were included from Jan 2011 to Jan 2020 in a single clinical centre. The short-term outcomes, overall survival (OS), and disease-free survival (DFS) were compared in different groups. A Cox regression analysis was conducted to identify independent risk factors for OS and DFS. Results. A total of 2047 CRC patients who underwent radical resection were included in the current study. Patients in the abnormal BUN group had a longer hospital stay (p=0.002) and more overall complications (p=0.001) than that of the normal BUN group. The abnormal CysC group had longer hospital stay (p

Transient receptor potential vanilloid type 4 (TRPV4) can function as an oncogene or tumor suppressor depending on the tumor types. However, little is known regarding the effect of TRPV4 in nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Southern China and Southeast Asia. We found that TRPV4 mRNA and protein levels were significantly upregulated in NPC tissues. In addition, activation of TRPV4 in NPC cell lines using GSK1016790A (100 nM) induced a Ca2+ influx, whereas pharmacological inhibition or gene knockdown of TRPV4 reduced the proliferation rates of NPC cells. TRPV4 knockdown also decreased the growth of tumor xenografts in vivo. Mechanistically, TRPV4-mediated tumorigenesis is dependent on the activation of Ca2+/calcineurin/calcineurin-nuclear factor of activated T cell 4 (NFAT4) signaling. Furthermore, NFAT4 protein level was overexpressed in NPC tissues and correlated positively with TRPV4. Taken together, TRPV4 promotes the malignant potential of NPC cells by activating NFAT4 signaling. Our findings highlight TRPV4-NFAT4 axis as a potential therapeutic target in NPC.

Abstract Purpose The purpose of the current study was to compare the postoperative complications, overall survival and disease-free survival in young and old gastric cancer patients after gastrectomy using propensity score matching (PSM). Methods Adult patients (aged ≥ 18 years) who underwent gastrectomy for gastric cancer in a single clinical center from January 2013 to December 2017 were enrolled continuously for retrospective analysis. To minimize the selection bias between the young and old groups, the PSM was conducted in this study. Results A total of 558 patients were included in this study, with 51 patients in the young group (aged ≤ 45 years) and 507 patients in the old group (aged > 45 years). After 1:1 matching according to PSM, 51 patients in the young group were matched to 51 patients in the old group. After PSM, there was no difference in the baseline information. In terms of short-term outcomes, no difference was found in operation time (P = 0.190), intraoperative blood loss (P = 0.336), retrieved lymph nodes (P = 0.948), blood transfusion (P = 0.339), postoperative hospital stay (P = 0.194), or postoperative complications (P = 0.477) between the two groups. For overall survival, no statistically significant difference was found in all stages (P = 0.383), stage I (P = 0.431), stage II (P = 0.875) or stage III (P = 0.446) gastric cancer. Furthermore, regarding disease-free survival, no differences were found between the two groups in all stages (P = 0.378), stage I (P = 0.431), stage II (P = 0.879) or stage III (P = 0.510) gastric cancer. Conclusion Age might not be an independent prognostic factor for short-term outcomes, OS, or DFS in gastric cancer patients who underwent gastrectomy. The pTNM stage of GC might be an independent prognostic factor for OS and DFS.

Abstract Background Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. Methods Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. Results Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. Conclusions Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.

Numerical simulation of the phase-change heat conduction process plays an important role in numerous engineering applications such as metal and alloy production and casting. Because of the increasing demands on the efficiency of the computational models utilized in advanced process control and optimization, high-performance computational models are becoming a necessary building block of practical applications. Thus, in this paper, we focus on accelerating the phase-change heat conduction simulations on GPUs. In addition to taking the advantage of thousands of GPU cores, the current paper presents a set of optimization methods to improve the resource usage of GPUs. The proposed methods include thread rescheduling, global function design, and a data caching mechanism, which helps establish an appropriate mapping from the numerical algorithm to the GPU hardware feature, thus remarkably enhancing the solving efficiency. We have validated the accuracy of the accelerated model with the Stefan problem and evaluated its performance with a three-dimensional steel solidification problem. A performance boost has been demonstrated, where the optimized GPU solver achieves a 333.6x speed-up compared to the non-parallel CPU solver. The performance characteristic of the accelerated solver makes it a powerful and promising tool for practical industrial usage.

BackgroundThe targeted therapy for lung cancer relies on prognostic genes and requires further research. No research has been conducted to determine the effect of endothelin-converting enzyme 2 (ECE2) in lung cancer.MethodsWe analyzed the expression of ECE2 in lung adenocarcinoma (LUAD) and normal adjacent tissues and its relationship with clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Immunohistochemical staining was used to further validate the findings. GO/KEGG enrichment analysis and gene set enrichment analysis (GSEA) of ECE2 co-expression were performed using R software. Data from TIMER, the GEPIA database, and TCGA were analyzed to determine the relationship between ECE2 expression and LUAD immune infiltration. To investigate the relationship between ECE2 expression levels and LUAD m6A modification, TCGA data and GEO data were analyzed.ResultsECE2 is highly expressed in various cancers including LUAD. ECE2 showed high accuracy in distinguishing tumor and normal sample results. The expression level of ECE2 in LUAD was significantly correlated with tumor stage and prognosis. GO/KEGG enrichment analysis showed that ECE2 was closely related to mitochondrial gene expression, ATPase activity and cell cycle. GSEA analysis showed that ECE2-related differential gene enrichment pathways were related to mitotic cell cycle, MYC pathway, PLK1 pathway, DNA methylation pathway, HIF1A pathway and Oxidative stress-induced cellular senescence. Analysis of the TIMER, GEPIA database, and TCGA datasets showed that ECE2 expression levels were significantly negatively correlated with B cells, CD4+ cells, M2 macrophages, neutrophils, and dendritic cells. TCGA and GEO datasets showed that ECE2 was significantly associated with m6A modification-related genes HNRNPC, IGF2BP1, IGF2BP3 and RBM1.ConclusionECE2 is associated with m6A modification and immune infiltration and is a prognostic biomarker in LUAD.

Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer.Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments.Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers.Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.

A chemical investigation of the Arctic-derived fungus Eutypella sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds 1–3 and 11–12) from rice medium and eight cytosporins (compounds 2 and 4–11) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (1), cytosporin Y (2), cytosporin Z (3), cytosporin Y1 (4), cytosporin Y2 (5), cytosporin Y3 (6), and cytosporin E1 (7), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (4) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound 1 contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (12) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds 6 and 7 was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from Eutypella sp. D-1 were evaluated. Unfortunately, only compounds 3, 6, 8, and 10–11 displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 μg/mL.

We assessed interactions between the astrocytic volume-regulated anion channel (VRAC) and aquaporin 4 (AQP4) in the supraoptic nucleus (SON). Acute SON slices and cultures of hypothalamic astrocytes prepared from rats received hyposmotic challenge (HOC) with/without VRAC or AQP4 blockers. In acute slices, HOC caused an early decrease with a late rebound in the neuronal firing rate of vasopressin neurons, which required activity of astrocytic AQP4 and VRAC. HOC also caused a persistent decrease in the excitatory postsynaptic current frequency, supported by VRAC and AQP4 activity in early HOC; late HOC required only VRAC activity. These events were associated with the dynamics of glial fibrillary acidic protein (GFAP) filaments, the late retraction of which was mediated by VRAC activity; this activity also mediated an HOC-evoked early increase in AQP4 expression and late subside in GFAP-AQP4 colocalization. AQP4 activity supported an early HOC-evoked increase in VRAC levels and its colocalization with GFAP. In cultured astrocytes, late HOC augmented VRAC currents, the activation of which depended on AQP4 pre-HOC/HOC activity. HOC caused an early increase in VRAC expression followed by a late rebound, requiring AQP4 and VRAC, or only AQP4 activity, respectively. Astrocytic swelling in early HOC depended on AQP4 activity, and so did the early extension of GFAP filaments. VRAC and AQP4 activity supported late regulatory volume decrease, the retraction of GFAP filaments, and subside in GFAP-VRAC colocalization. Taken together, astrocytic morphological plasticity relies on the coordinated activities of VRAC and AQP4, which are mutually regulated in the astrocytic mediation of HOC-evoked modulation of vasopressin neuronal activity.

AIM:To evaluate the mitomycin-C(MMC)0.02% efficacy in preventing haze after trans-epithelial photorefractive keratectomy(Trans-PRK)in the treatment of the high myopia. METHODS: Retrospective case series. Trans-PRK were performed on 142 eyes with a preoperative spherical equivalent. They were divided into with 0.02% MMC(MMC group)and without MMC(control)groups. In MMC group there were 94 eyes with MMC 0.02%; in control group there were 48 eyes. Patients were treated with an intraoperative application of MMC 0.02% for 30-45s depending on refractive error in MMC group. After surgery, fluorometholone 0.1% eye drops were used for 4mo in all groups. The mean follow-up time was 6mo. The regression trees were used to analyse the relationship between different related factors and haze. RESULTS:Haze was quantified with Fantes. Incidence of haze was 8.5% eyes in MMC group and 33.3% in without MMC group(P=0.001). In the regression trees, optical zone and ablation depth MAX were related to haze(P5.6mm, ablation depth MAX becomes the main factor for haze.CONCLUSION: The design of optical zone and ablation depth MAX in Trans-PRK should be considered for the treatment of the high myopia with thin cornea and abnormal corneal morphology. MMC 0.02% was effective in preventing haze after Trans-PRK in the treatment of the high myopia.