Immunohistochemistry identifies E-cadherin, N-cadherin and focal adhesion kinase (FAK) as predictors of stage I non-small cell lung carcinoma spread through the air spaces (STAS), and the combinations as prognostic factors.

Background: Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. Methods: E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. Conclusions: E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.

Correlation between the TyG-BMI index and carotid plaque characteristics in middle-aged and elderly patients with acute myocardial infarction.

OBJECTIVE: The aim of this study is to investigate the correlation between the triglyceride-glucose-body mass index (TyG-BMI) and the characteristics of various carotid plaques in middle-aged and elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted on 380 patients with AMI hospitalized in the Cardiology Department of Kaifeng Central Hospital. Based on carotid ultrasound results, patients were divided into the following two groups: the stable plaque group and the unstable plaque group. Additionally, a control group comprising 380 healthy individuals visiting the hospital's physical examination center during the same timeframe was established. Fasting venous blood samples were collected from all participants to measure blood glucose and triglyceride. The baseline TyG-BMI index was calculated using the formula Ln [fasting triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]×BMI. The correlation between different plaque groups and the TyG-BMI index was analyzed. RESULTS: The TyG-BMI index was significantly higher in the unstable plaque group compared to the stable plaque group, with values of 252.81±29.99 and 201.92±28.72, respectively (P = 0.034). Spearman's correlation analysis showed a positive correlation between the instability of carotid plaques and the TyG-BMI index in patients with AMI (r = 0.521, P = 0.003). Logistic regression analysis indicated that the TyG-BMI index was an important risk factor for unstable carotid plaques in patients with AMI (OR = 2.691, 95% CI: 1.169-4.123). CONCLUSION: The findings of this study suggest that an elevated TyG-BMI index significantly increases the risk of unstable carotid plaques in patients with AMI, making it an important risk factor for carotid plaque instability.

The use of acupuncture for addressing neurological and neuropsychiatric symptoms in patients with long COVID: a systematic review and meta-analysis.

Importance: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID. Objective: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients. Data Sources: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers. Study Selection: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. Data Extraction and Synthesis: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I2. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940). Main outcomes and measures: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia. Results: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01). Conclusion and relevance: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms. Systematic Review Registration: PROSPERO, identifier [CRD42022354940].

Discovery of RGT-018: a Potent, Selective and Orally Bioavailable SOS1 Inhibitor for KRAS-driven Cancers.

KRAS is the most frequently dysregulated oncogene with high prevalence in NSCLC, colorectal cancer, and pancreatic cancer. FDA-approved sotorasib and adagrasib provide breakthrough therapies for cancer patients with KRASG12C mutation. However, there is still high unmet medical need for new agents targeting broader KRAS-driven tumors. An emerging and promising opportunity is to develop a pan KRAS inhibitor by suppressing the upstream protein SOS1. SOS1 is a key activator of KRAS and facilitates the conversion of GDP-bound KRAS state to GTP-bound KRAS state. Binding to its catalytic domain, small molecule SOS1 inhibitor has demonstrated the ability to suppress KRAS activation and cancer cell proliferation. RGT-018, a potent and selective SOS1 inhibitor, was identified with optimal drug-like properties. In vitro, RGT-018 blocked the interaction of KRAS:SOS1 with single digit nM potency and is highly selective against SOS2. RGT-018 inhibited KRAS signaling and the proliferation of a broad spectrum of KRAS-driven cancer cells as a single agent in vitro. Further enhanced anti-proliferation activity was observed when RGT-018 was combined with MEK, KRASG12C, EGFR or CDK4/6 inhibitors. Oral administration of RGT-018 inhibited tumor growth and suppressed KRAS signaling in tumor xenografts in vivo. Combination with MEK or KRASG12C inhibitors led to significant tumor regression. Furthermore, RGT-018 overcame the resistance to the approved KRASG12C inhibitors caused by clinically acquired KRAS mutations either as a single agent or in combination. RGT-018 displayed promising pharmacological properties for combination with targeted agents to treat a broader KRAS-driven patient population.

Established the prediction model of early-stage non-small cell lung cancer spread through air spaces (STAS) by radiomics and genomics features.

BACKGROUND: This study was aimed to establish a prediction model for spread through air spaces (STAS) in early-stage non-small cell lung cancer based on imaging and genomic features. METHODS: We retrospectively collected 204 patients (47 STAS+ and 157 STAS-) with non-small cell lung cancer who underwent surgical treatment in the Jinling Hospital from January 2021 to December 2021. Their preoperative CT images, genetic testing data (including next-generation sequencing data from other hospitals), and clinical data were collected. Patients were randomly divided into training and testing cohorts (7:3). RESULTS: The study included a total of 204 eligible patients. STAS were found in 47 (23.0%) patients, and no STAS were found in 157 (77.0%) patients. The receiver operating characteristic curve showed that radiomics model, clinical genomics model, and mixed model had good predictive performance (area under the curve [AUC] = 0.85; AUC = 0.70; AUC = 0.85). CONCLUSIONS: The prediction model based on radiomics and genomics features has a good prediction performance for STAS.

Targeted metabolomics revealed the seasonal plasticity of skin color and pigment metabolites in ornamental koi carp.

The koi carp is an ornamental fish that was obtained through artificial selection from the common carp (Cyprinus carpio L.). The most economically important traits of koi are their beautiful skin patterns in bright colors. As seasonality is an important factor in the biology and ecology of fish, we thus assumed that seasonal changes are involved in regulating the formation of skin color and patterns of koi carp. The white, red, cyan, and black skin colors from four varieties of scaleless koi carp (Doitsu Shiromuji (W), Doitsu Kohaku (WR), Doitsu Showa Sanke (WRI), and Kumonryu (WI)) were evaluated using the CIELab color space (lightness, redness, and yellowness) in different seasons. Compared to winter, the yellowness of the white color in all koi varieties decreased in summer and autumn. The black skin color areas in WRI and WI koi increased in summer and autumn compared to winter. The yellowness of the red color decreased only in WRI koi, while no changes were observed in WR koi. Targeted metabolomics analysis revealed that the levels of the structural pigment guanine of all koi varieties showed significant seasonal variation. Of seven detected carotenoids, the zeaxanthin and tunaxanthin contents in W, WI, and WRI koi changed with the seasons, while none of the carotenoids in WR koi were altered. Of the seven potential regulatory metabolites, epinephrine, melatonin, and cyclic adenosine monophosphate (cAMP) in all four koi varieties showed the highest levels in winter. A correlation analysis suggested that the seasonal changes in white skin color occurred through the epinephrine-cAMP pathway; melanin-dependent and carotenoid-dependent skin color changes occurred through melatonin in koi carp. This study demonstrated the seasonal plasticity of skin color in koi carp regulated by melatonin and epinephrine, associating with variety and color specificity.

Turning inward in difficulties: R&D human resource slack, technological diversification, and independent innovation.

Independent innovation emphasizes the self-reliance and control of all key links. Slack resources within an organization, especially for innovation, are the critical resources that are controllable for independent innovation. However, existing research still lacks evidence on the areas of slack innovation resources and independent innovation for deeper exploration. This research addresses this gap by providing an empirical analysis of the relationship between R&D human resource slack and firms' independent innovation. Based on the unbalanced panel data of China's listed manufacturing firms for eleven years, this research explores the effects of R&D human resource slack on firms' independent innovation, the mediating mechanism of technological diversification, and the boundary effects of top management team functional heterogeneity. The results reveal that R&D human resource slack positively affects firms' independent innovation; R&D human resource slack can promote firms' independent innovation through related technological diversification, while the mediating effect of unrelated technological diversification is not statistically significant; the top management team functional heterogeneity strengthens the positive impact of R&D human resource slack on firm independent innovation.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice. Methods: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality. Results: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs. Conclusion: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

Efficacy and safety of Chinese herbal medicine to prevent and treat COVID-19 household close contacts in Hong Kong: an open-label, randomized controlled trial.

Objectives: To evaluate the efficacy and safety of CHM in the prevention of COVID-19 infection and treatment for COVID-19 related symptoms. Design: Prospective open-label randomized controlled trial. Setting: Participants' home in Hong Kong. Participants: Participants who had household close contact with COVID-19-infected family members. Interventions: Close contacts were stratified into 4 groups (cohort A, B, C, D) based on symptoms and infection status and were randomized in 4:1 ratio to receive CHM granules (9g/sachet, two times daily) or blank control for 7 days with 2 weeks of follow-up. Main outcome measures: The primary outcome measure was the rate of positive nucleic acid tests. Secondary outcomes were the proportion of developed COVID-19 related symptoms and adverse events during the whole 3-week study period. Subgroup analysis was used to evaluate demographic factors associated with positive infection rates. Results: A total of 2163 contacts were enrolled and randomly assigned to the CHM group (1720 contacts) and blank control (443 contacts) group. During the 21 days, the rate of PCR-positive cases in cohort A was markedly lower in the CHM group (3.6%) compared to the control group (7.0%) (P=0.036). Overall, the rate of infection in the CHM group was significantly lower than that in the control group (10.69% vs. 6.03%; RR 0.56, 95% CI 0.39-0.82) after 7-day treatment. No serious adverse events were reported during the medication period. Conclusion: The preliminary findings indicate that CHM may be effective and safe in preventing COVID-19. Future double-blind, randomized controlled trials and long-term follow-up are needed to fully evaluate the efficacy of CHM in a larger contact population. Clinical trial registration: ClinicalTrials.gov, identifier NCT05269511.

Effective cryopreservation of human brain tissue and neural organoids.

Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

m6A RNA Methylation and Implications for Hepatic Lipid Metabolism.

This review presents a summary of recent progress in research on the N6-methyladenosine (m6A) modification and regulatory roles in hepatic lipid metabolism. As the most abundant internal modification of eukaryotic RNA, the m6A modification is a dynamic and reversible process of the m6A enzyme system, which includes writers, erasers, and readers. m6A methylation depressed lipid synthesis and facilitated lipolysis in liver. The depletion of m6A methyltransferase Mettl14/Mettl3 raised fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1), acetyl-CoA carboxylase (ACC), and elongase of very long chain fatty acids 6 (ELOVL6) in rodent liver, causing increases in liver weight, triglyceride (TG) production, and content in hepatocytes. FTO catalyzed m6A demethylation and the suppression m6A reader YTHDC2 promoted hepatocellular TG generation and hepatic steatosis in C57BL/6 mice through sterol regulatory element-binding protein 1c (SREBP-1c) signaling pathway, which upregulated the lipogenic genes FAS, SCD1, ACC, recombinant acetyl coenzyme a carboxylase alpha, and cell death-inducing DNA fragmentation factor-like effector C (CIDEC). Furthermore, FTO overexpression did not only enhance mitochondrial fusion to impair mitochondrial function and lipid oxidation but also promoted lipid peroxidation, accompanied by excessive TG in hepatocytes and rodent liver. Elevated m6A modification potently suppressed hepatic lipid accumulation, while the shrinkage of m6A modification arose hepatic lipid deposition. These findings have highlighted the beneficial role of m6A RNA methylation in hepatic lipid metabolism, potentially protecting liver from lipid metabolic disorders.

Cryo-EM structures reveal two allosteric inhibition modes of PI3KαH1047R involving a re-shaping of the activation loop.

PI3Kα is a lipid kinase that phosphorylates PIP2 and generates PIP3. The hyperactive PI3Kα mutation, H1047R, accounts for about 14% of breast cancer, making it a highly attractive target for drug discovery. Here, we report the cryo-EM structures of PI3KαH1047R bound to two different allosteric inhibitors QR-7909 and QR-8557 at a global resolution of 2.7 Å and 3.0 Å, respectively. The structures reveal two distinct binding pockets on the opposite sides of the activation loop. Structural and MD simulation analyses show that the allosteric binding of QR-7909 and QR-8557 inhibit PI3KαH1047R hyper-activity by reducing the fluctuation and mobility of the activation loop. Our work provides a strong rational basis for a further optimization and development of highly selective drug candidates to treat PI3KαH1047R-driven cancers.

Glutamicibacter nicotianae AT6: A new strain for the efficient biodegradation of tilmicosin.

The degradation of tilmicosin (TLM), a semi-synthetic 16-membered macrolide antibiotic, has been receiving increasing attention. Conventionally, there are three tilmicosin degradation methods, and among them microbial degradation is considered the best due to its high efficiency, eco-friendliness, and low cost. Coincidently, we found a new strain, Glutamicibacter nicotianae sp. AT6, capable of degrading high-concentration TLM at 100 mg/L with a 97% removal efficiency. The role of tryptone was as well investigated, and the results revealed that the loading of tryptone had a significant influence on TLM removals. The toxicity assessment indicated that strain AT6 could efficiently convert TLM into less-toxic substances. Based on the identified intermediates, the degradation of TLM by AT6 processing through two distinct pathways was then proposed.

A predictive model for post-thoracoscopic surgery pulmonary complications based on the PBNN algorithm.

We constructed an early prediction model for postoperative pulmonary complications after thoracoscopic surgery using machine learning and deep learning algorithms. The artificial intelligence prediction models were built in Python, primarily using artificial intelligencealgorithms including both machine learning and deep learning algorithms. Correlation analysis showed that postoperative pulmonary complications were positively correlated with age and surgery duration, and negatively correlated with serum albumin. Using the light gradient boosting machine(LGBM) algorithm, weighted feature engineering revealed that single lung ventilation duration, history of smoking, surgery duration, ASA score, and blood glucose were the main factors associated with postoperative pulmonary complications. Results of artificial intelligence algorithms for predicting pulmonary complications after thoracoscopy in the test group: In terms of accuracy, the two best algorithms were Logistic Regression (0.831) and light gradient boosting machine(0.827); in terms of precision, the two best algorithms were Gradient Boosting (0.75) and light gradient boosting machine (0.742); in terms of recall, the three best algorithms were gaussian naive bayes (0.581), Logistic Regression (0.532), and pruning Bayesian neural network (0.516); in terms of F1 score, the two best algorithms were LogisticRegression (0.589) and pruning Bayesian neural network (0.566); and in terms of Area Under Curve(AUC), the two best algorithms were light gradient boosting machine(0.873) and pruning Bayesian neural network (0.869). The results of this study suggest that pruning Bayesian neural network (PBNN) can be used to assess the possibility of pulmonary complications after thoracoscopy, and to identify high-risk groups prior to surgery.

Artificial intelligence algorithms for predicting post-operative ileus after laparoscopic surgery.

Objective: By constructing a predictive model using machine learning and deep learning technologies, we aim to understand the risk factors for postoperative intestinal obstruction in laparoscopic colorectal cancer patients, and establish an effective artificial intelligence-based predictive model to guide individualized prevention and treatment, thus improving patient outcomes. Methods: We constructed a model of the artificial intelligence algorithm in Python. Subjects were randomly assigned to either a training set for variable identification and model construction, or a test set for testing model performance, at a ratio of 7:3. The model was trained with ten algorithms. We used the AUC values of the ROC curves, as well as accuracy, precision, recall rate and F1 scores. Results: The results of feature engineering composited with the GBDT algorithm showed that opioid use, anesthesia duration, and body weight were the top three factors in the development of POI. We used ten machine learning and deep learning algorithms to validate the model, and the results were as follows: the three algorithms with best accuracy were XGB (0.807), Decision Tree (0.807) and Neural DecisionTree (0.807); the two algorithms with best precision were XGB (0.500) and Decision Tree (0.500); the two algorithms with best recall rate were adab (0.243) and Decision Tree (0.135); the two algorithms with highest F1 score were adab (0.290) and Decision Tree (0.213); and the three algorithms with best AUC were Gradient Boosting (0.678), XGB (0.638) and LinearSVC (0.633). Conclusion: This study shows that XGB and Decision Tree are the two best algorithms for predicting the risk of developing ileus after laparoscopic colon cancer surgery. It provides new insight and approaches to the field of postoperative intestinal obstruction in colorectal cancer through the application of machine learning techniques, thereby improving our understanding of the disease and offering strong support for clinical decision-making.

Nocardia rubra cell-wall skeleton mitigates whole abdominal irradiation-induced intestinal injury via regulating macrophage function.

Background: Ionizing radiation (IR)-induced intestinal injury is a major side effect and dose-limiting toxicity in patients receiving radiotherapy. There is an urgent need to identify an effective and safe radioprotectant to reduce radiation-induced intestinal injury. Immunoregulation is considered an effective strategy against IR-induced injury. The purpose of this article was to investigate the protective effect of Nocardia rubra cell wall skeleton (Nr-CWS), an immunomodulator, on radiation-induced intestinal damage and to explore its potential mechanism. Methods: C57BL/6 J male mice exposed to 12 Gy whole abdominal irradiation (WAI) were examined for survival rate, morphology and function of the intestine and spleen, as well as the gut microbiota, to comprehensively evaluate the therapeutic effects of Nr-CWS on radiation-induced intestinal and splenetic injury. To further elucidate the underlying mechanisms of Nr-CWS-mediated intestinal protection, macrophages were depleted by clodronate liposomes to determine whether Nr-CWS-induced radioprotection is macrophage dependent, and the function of peritoneal macrophages stimulated by Nr-CWS was detected in vitro. Results: Our data showed that Nr-CWS promoted the recovery of intestinal barrier function, enhanced leucine-rich repeat-containing G protein-coupled receptor 5+ intestinal stem cell survival and the regeneration of intestinal epithelial cells, maintained intestinal flora homeostasis, protected spleen morphology and function, and improved the outcome of mice exposed to 12 Gy WAI. Mechanistic studies indicated that Nr-CWS recruited macrophages to reduce WAI-induced intestinal damage. Moreover, macrophage depletion by clodronate liposomes blocked Nr-CWS-induced radioprotection. In vitro, we found that Nr-CWS activated the nuclear factor kappa-B signaling pathway and promoted the phagocytosis and migration ability of peritoneal macrophages. Conclusions: Our study suggests the therapeutic effect of Nr-CWS on radiation-induced intestinal injury, and provides possible therapeutic strategy and potential preventive and therapeutic drugs to alleviate it.

Expression analysis and antiviral activity of koi carp (Cyprinus carpio) viperin against carp edema virus (CEV).

Viperin, also known as radical S-Adenosyl methionine domain containing 2 (RSAD2), is an IFN stimulated protein that plays crucial roles in innate immunity. Here, we identified a viperin gene from the koi carp (Cyprinus carpio) (kVip). The ORF of kVip is 1047 bp in length, encoding a polypeptide of 348 amino acids with neither signal peptide nor transmembrane protein. The predicted molecular weight is 40.37 kDa and the isoelectric point is 7.7. Multiple sequence alignment indicated that putative kVip contains a radical SAM superfamily domain and a conserved C-terminal region. kVip was highly expressed in the skin and spleen of healthy koi carps, and significantly stimulated in both natural and artificial CEV-infected koi carps. In vitro immune stimulation analysis showed that both extracellular and intracellular poly (I: C) or poly (dA: dT) caused a significant increase in kVip expression of spleen cells. Furthermore, intraperitoneal injection of recombinant kVip (rkVip) not only reduced the CEV load in the gills, but also improved the survival of koi carps following CEV challenge. Additionally, rkVip administration effectively regulated inflammatory and anti-inflammatory cytokines (IL-6, IL-1ß, TNF-α, IL-10) and interferon-related molecules (cGAS, STING, MyD88, IFN-γ, IFN-α, IRF3 and IRF9). Collectively, kVip effectively responded to CEV infection and exerted antiviral function against CEV partially by regulation of inflammatory and interferon responses.

Correlation of skin color and plasma carotenoid-related metabolites of ornamental koi carp under temperature fluctuations.

The skin color of koi carp (Cyprinus carpio L.) is one of the traits that most influence their ornamental and economic values. The present study suggested the effects of temperature fluctuation on koi carp in terms of skin color and plasma carotenoids and related-metabolites. The main results were as follows. (1) The vulnerability of koi skin color to acute temperature stress was in the order of white koi> black koi> yellow koi. Both high- (25°C-30°C-25°C) and low-temperature (25°C-20°C-25°C) fluctuations tended to decrease the saturation of white koi. The temperature fluctuation had little effects on the skin color of black and yellow koi. (2) Targeted metabolomics analysis indicated that the effects of cooling stress on oxycarotenoids of all five koi varieties were reversible. The plasma oxycarotenoids in mirror koi with all colors were insensitive to acute heat stress. However, the cooling process from a high temperature (30°C-25°C) still made contributions to the increase of oxycarotenoids. (3) The principal component analysis confirmed the deviation of carotenoid-related metabolites after high temperature fluctuation and the reversibility after low temperature fluctuation. Finally, the correlation analysis revealed that koi skin brightness was negatively correlated with the plasma guanine content and that temperature fluctuations might change koi skin brightness via the L(-)-epinephrine-guanine pathway. The red hue and yellow hue were negatively correlated with the oxycarotenoids in plasma, suggesting that oxycarotenoids were favorable for enhancing koi skin color saturation. Overall, this study revealed the direct action of temperature fluctuations on the skin color and carotenoid-related metabolites of koi.

Simulating contamination of the operator and surrounding environment during wound debridement through fluorescent labelling.

We investigated the contamination of the operator and the surrounding environment during wound debridement through simulated operations using fluorescent labelling. On-site simulated operation assessment was performed before and after the training. Oranges and square towels were used to simulate wounds and the inpatient units, respectively. Fluorescent powder was applied to the surfaces. Operations on oranges simulated bedside debridement, and the postoperative distribution of the fluorescent powder was employed to reflect the contamination of the operator and the surrounding environment. During the pre-training assessment, contamination was observed in 28 of the 29 trainees. The commonly contaminated parts were the extensor side of the forearm, middle abdomen, upper abdomen, and hands. The right side of the operating area was contaminated in 24 trainees. During the post-training assessment, contamination was observed in 13 of the 15 trainees. The commonly parts were the hands, extensor side of the forearm, and the lower abdomen. The front, back, left, and right sides of the operating area were contaminated in 12, 9, 11, and 14 trainees, respectively. Contamination of the treatment cart was observed in 5 trainees. Operator and the surrounding environment can be contaminated during wound debridement. Attention should be paid to hand hygiene, wearing and changing of work clothes, and disinfection of the surrounding environment. Moreover, regular training is recommended.