Detection and population genetic analysis of Aedes albopictus (Diptera: Culicidae) based on knockdown resistance (kdr) mutations in the Yangtze River basin of China.

BACKGROUND: Aedes albopictus is an important vector of chikungunya, dengue, yellow fever and Zika viruses. Insecticides are often the most effective tools for rapidly decreasing the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has led to the selection of resistant mosquito populations worldwide. Mutations in the voltage-gated sodium channel (VGSC) gene are one of the main drivers of insecticide resistance in Ae. albopictus and are also known as "knockdown resistance" (kdr) mutations. Knowledge about genetic mutations associated with insecticide resistance is a prerequisite for developing techniques for rapid resistance diagnosis. Here, we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. albopictus from the Yangtze River Basin, China; METHODS: Here, we report the results of PCR genotyping of kdr mutations in 541 Ae. albopictus specimens from 22 sampling sites in 7 provinces and municipalities in the Yangtze River Basin. Partial DNA sequences of domain II and domain III of the VGSC gene were amplified. These DNA fragments were subsequently sequenced to discover the possible genetic mutations mediating knockdown resistance (kdr) to pyrethroids. The frequency and distribution of kdr mutations were assessed in 22 Ae. albopictus populations. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations had a single or multiple origins; RESULTS: The kdr mutation at the 1016 locus had 2 alleles with 3 genotypes: V/V (73.38%), V/G (26.43%) and G/G (0.18%). The 1016G homozygous mutation was found in only one case in the CQSL strain in Chongqing, and no 1016G mutations were detected in the SHJD (Shanghai), NJDX (Jiangsu) or HBQN (Hubei) strains. A total of 1532 locus had two alleles and three genotypes, I/I (88.35%), I/T (8.50%) and T/T (3.14%). A total of 1534 locus had four alleles and six genotypes: F/F (49.35%), F/S (19.96%), F/C (1.48%) and F/L (0.18%); S/S (23.66%); and C/C (5.36%). Haplotypes with the F1534C mutation were found only in Ae. albopictus populations in Chongqing and Hubei, and C1534C was found only in three geographic strains in Chongqing. Haplotypes with the 1534S mutation were found only in Ae. albopictus populations in Sichuan and Shanghai. F1534L was found only in HBYC. The Ae. albopictus populations in Shanghai were more genetically differentiated from those in the other regions (except Sichuan), and the genetic differentiation between the populations in Chongqing and those in the middle-lower reaches of the Yangtze River (Huber, Jiangsu, Jiangxi, and Anhui) was lower. Shanghai and Sichuan displayed low haplotype diversity and low nucleotide diversity. Phylogenetic analysis and sequence comparison revealed that the 1016 locus was divided into three branches, with the Clade A and Clade B branches bearing the 1016 mutation occurring mostly in Jiangsu and the Clade C branch bearing the 1016 mutation occurring mostly in Chongqing, suggesting at least two origins for 1016G. IIIS6 phylogenetic analysis and sequence comparison revealed that F1534S, F1534C and I1532T can be divided into two branches, indicating that IIIS6 has two origins; CONCLUSIONS: Combined with the distribution of kdr mutations and the analysis of population genetics, we infer that besides the local selection of pyrethroid resistance mutations, dispersal and colonization of Ae. albopictus from other regions may explain why kdr mutations are present in some Ae. albopictus populations in the Yangtze River Basin.

ROS induced pyroptosis in inflammatory disease and cancer.

Pyroptosis, a form of caspase-1-dependent cell death, also known as inflammation-dependent death, plays a crucial role in diseases such as stroke, heart disease, or tumors. Since its elucidation, pyroptosis has attracted widespread attention from various sectors. Reactive oxygen species (ROS) can regulate numerous cellular signaling pathways. Through further research on ROS and pyroptosis, the level of ROS has been revealed to be pivotal for the occurrence of pyroptosis, establishing a close relationship between the two. This review primarily focuses on the molecular mechanisms of ROS and pyroptosis in tumors and inflammatory diseases, exploring key proteins that may serve as drug targets linking ROS and pyroptosis and emerging fields targeting pyroptosis. Additionally, the potential future development of compounds and proteins that influence ROS-regulated cell pyroptosis is anticipated, aiming to provide insights for the development of anti-tumor and anti-inflammatory drugs.

Study on the Mechanism of Yadanzi Oil in Treating Lung Cancer Based on Network Pharmacology and Molecular Docking Technology.

Brucea javanica oil emulsion (BJOE) is a compound Chinese medicine used for treating various cancers, such as lung cancer. However, the exact mechanism of its antilung cancer active ingredient remains unclear. This study aims to explore and validate the effective active ingredients and mechanism of action of BJOE in the treatment of lung cancer through network pharmacology, molecular docking technology, and cell experiments. The results showed that there were 13 active ingredients, 136 target genes, and 42 disease target-coexpressed genes in BJOE. The molecular docking results indicated that the main active components of the oil emulsion, YD1 (ß-sitosterol), YD2 (luteolin), and YD3 (bruceitol), could stably bind to TP53 and MAPK1. Furthermore, the commercially available ß-sitosterol luteolin was used as a representative compound to conduct cell experiments to verify its anticancer activity and mechanism. It was found that luteolin can inhibit the proliferation better than ß-sitosterol and the activity of lung cancer cells by regulating the expression of related proteins through the P53/MAPK1 signaling pathway. This study combines network pharmacology prediction with experiments to demonstrate the "multicomponent, multitarget, multipathway" approach of B. javanica oil emulsion in treating lung cancer.

Mechanism of ameliorating cerebral ischemia/reperfusion injury by antioxidant inhibition of autophagy based on network pharmacology and experimental verification.

Cerebral ischemia-reperfusion injury (CIRI) is one of the most difficult challenges in cerebrovascular disease research. It is primarily caused by excessive autophagy induced by oxidative stress. Previously, a novel compound X5 was found, and the excellent antioxidant activity of it was verified in this study. Moreover, network pharmacological analysis suggested that compound X5 was closely associated with autophagy and the mTOR pathway. In vitro, X5 could significantly inhibit the expression of autophagy proteins Beclin-1 and LC3-ß, which are induced by H2O2, and promote the expression of SIRT1. In vivo, compound X5 significantly reduced the infarct size and improved the neurological function scores in the middle cerebral artery occlusion (MCAO) model of rats. In conclusion, ROS-induced autophagy is closely related to mTOR, SIRT1 and others, and X5 holds promise as a candidate for the treatment of CIRI.

Artificial intelligence in cardiology: a bibliometric study.

OBJECTIVES: To perform a comprehensive bibliometric analysis of global publications on the applications of artificial intelligence (AI) in cardiology. METHODS: Documents related to AI in cardiology published between 2002 and 2022 were retrieved from Web of Science Core Collection. R package "bibliometrix", VOSviewers and Microsoft Excel were applied to perform the bibliometric analysis. RESULTS: A total of 4332 articles were included. United States topped the list of countries publishing articles, followed by China and United Kingdom. The Harvard University was the institution that contributed the most to this field, followed by University of California System and University of London. Disease risk prediction, diagnosis, treatment, disease detection, and prognosis assessment were the research hotspots for AI in cardiology. CONCLUSIONS: Enhancing cooperation between different countries and institutions is a critical step in leading to breakthroughs in the application of AI in cardiology. It is foreseeable that the application of machine learning and deep learning in various areas of cardiology will be a research priority in the coming years.

Possible potential spread of Anopheles stephensi, the Asian malaria vector.

BACKGROUND: Anopheles stephensi is native to Southeast Asia and the Arabian Peninsula and has emerged as an effective and invasive malaria vector. Since invasion was reported in Djibouti in 2012, the global invasion range of An. stephensi has been expanding, and its high adaptability to the environment and the ongoing development of drug resistance have created new challenges for malaria control. Climate change is an important factor affecting the distribution and transfer of species, and understanding the distribution of An. stephensi is an important part of malaria control measures, including vector control. METHODS: In this study, we collected existing distribution data for An. stephensi, and based on the SSP1-2.6 future climate data, we used the Biomod2 package in R Studio through the use of multiple different model methods such as maximum entropy models (MAXENT) and random forest (RF) in this study to map the predicted global An. stephensi climatically suitable areas. RESULTS: According to the predictions of this study, some areas where there are no current records of An. stephensi, showed significant areas of climatically suitable for An. stephensi. In addition, the global climatically suitability areas for An. stephensi are expanding with global climate change, with some areas changing from unsuitable to suitable, suggesting a greater risk of invasion of An. stephensi in these areas, with the attendant possibility of a resurgence of malaria, as has been the case in Djibouti. CONCLUSIONS: This study provides evidence for the possible invasion and expansion of An. stephensi and serves as a reference for the optimization of targeted monitoring and control strategies for this malaria vector in potential invasion risk areas.

The effect of artificial light at night (ALAN) on the characteristics of diapause of Aedes albopictus.

BACKGROUND: Recently, the effect of artificial light at night (ALAN) on the physiology and behavior of insects has gradually attracted the attention of researchers and has become a new research topic. Aedes albopictus is an important vector that poses a great public health risk. Further studies on the diapause of Ae. albopictus can provide a basis for new vector control, and it is also worth exploring whether the effect of ALAN on the diapause of Ae. albopictus will provide a reference for the prevention and control of infectious diseases mediated by Ae. albopictus. METHODS: In this study, we experimentally studied the diapause characteristics of different geographical strains of Ae. albopictus under the interference of ALAN, explored the effect of ALAN on the diapause of Ae. albopictus and explored the molecular mechanism of ALAN on the diapause process through RNA-seq. RESULTS: As seen from the diapause incidence, Ae. albopictus of the same geographic strain showed a lower diapause incidence when exposed to ALAN. The differentially expressed genes (DEGs) were mainly enriched in signaling and metabolism-related pathways in the parental females and diapause eggs of the ALAN group. CONCLUSIONS: ALAN inhibits Ae. albopictus diapause. In the short photoperiod induced diapause of Ae. albopictus in temperate strain Beijing and subtropical strain Guangzhou, the disturbance of ALAN reduced the egg diapause rate and increased the egg hatching rate of Ae. albopictus, and the disturbance of ALAN also shortened the life cycle of Ae. albopictus eggs after hatching.

Discovery of Pyroptosis-inducing Drugs and Antineoplastic Activity Based on the ROS/ER Stress/Pyroptosis Axis.

BACKGROUND: Pyroptosis, a cell death process triggered by chemotherapy drugs, has emerged as a highly promising mechanism for combating tumors in recent years. As the lead of new drugs, natural products play an important role in the discovery of anticancer drugs. Compared to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior safety profile. Among a series of MFHNP molecular skeletons, this study found that only benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity of 1 remains to be improved. AIMS: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by modifying the chalcone structure. METHODS: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis, several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer activity was tested by MTT assay, and morphological indications of pyroptosis were observed in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore, to improve the activity of the chalcone skeleton, the anticancer group 3,4,5- trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed, synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally, a quantitative structure-activity relationship (QSAR) model was established using the eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore. Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular mechanisms of pyroptosis induced by the active compound. RESULTS: α, ß-unsaturated ketone was the functional group of the chalcone skeleton and played a pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients (R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft tumors. CONCLUSION: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis axis and is a kind of promising pyroptosis inducer.

The effect and mechanism of novel methoxy curcumin analogs based on network pharmacology.

In this study, a series of novel compounds were synthesized by introducing the 3,4,5-trimethoxyphenyl and isatin groups into the monocarbonyl skeleton of curcumin. The possible biological activities and potential targets for these compounds were explored through network pharmacology. The results revealed that these compounds could significantly inhibit production of the inflammatory factors IL-6 and TNF-α, and suppress phosphorylation of the extracellular signal-regulated kinase (ERK) protein. Moreover, molecular docking experiments showed that the ERK protein was the potential target for these compounds. In summary, this study, through network pharmacology, presents a novel series of methoxy curcumin analogs as potent anti-inflammatory drugs.

Mannose attenuates intestinal epithelial tight junction damage in experimental colitis mice by activating the AXIN-AMPK pathway.

Mannose is a unique natural sugar that can be found in a variety of fruits and vegetables. During the past decades, mannose has been reported to be effective in promoting immune tolerance and suppressing inflammatory diseases. Metabolic dysfunction and altered inflammation have clear implications for the development and progression of inflammatory diseases. Herein, we intended to reveal the molecular mechanism of mannose in protecting against intestinal epithelial damage in experimental colitis. We showed that mannose treatment significantly attenuated dextran sodium sulfate (DSS)-induced intestinal barrier damage. The AMPK pathway was responsible for the mannose-mediated protective effect in DSS-induced intestinal epithelial damage. Mechanistically, mannose promoted the axis inhibition protein (AXIN)-based AMPK activation, thereby preventing mitochondrial dysfunction and tight junction disruption in response to the DSS challenge. Cumulatively, the results indicate the use of mannose as a novel approach to treat IBD and other diseases involving tight junction dysfunction. The therapeutic effect of mannose is related to its regulatory function in AMPK pathway activation.

Mannan-binding lectin ameliorates renal fibrosis by suppressing macrophage-to-myofibroblast transition.

Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL-/-) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL-/- macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-ß) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.

Cell fusing agent virus isolated from Aag2 cells does not vertically transmit in Aedes aegypti via artificial infection.

BACKGROUND: Cell fusing agent virus (CFAV) was the first insect-specific virus to be characterized, and has been reported to negatively influence the growth of arboviruses such as dengue, Zika, and La Cross, making it a promising biocontrol agent for mosquito-borne disease prevention. Aedes aegypti Aag2 cells were naturally infected with CFAV. However, the ability of this virus to stably colonize an Ae. aegypti population via artificial infection and how it influences the vector competence of this mosquito have yet to be demonstrated. METHODS: CFAV used in this study was harvested from Aag2 cells and its complete genome sequence was obtained by polymerase chain reaction and rapid amplification of complementary DNA ends, followed by Sanger sequencing. Phylogenetic analysis of newly identified CFAV sequences and other sequences retrieved from GenBank was performed. CFAV stock was inoculated into Ae. aegypti by intrathoracic injection, the survival of parental mosquitoes was monitored and CFAV copies in the whole bodies, ovaries, and carcasses of the injected F0 generation and in the whole bodies of the F1 generation on different days were examined by reverse transcription-quantitative polymerase chain reaction. RESULTS: The virus harvested from Aag2 cells comprised a mixture of three CFAV strains. All genome sequences of CFAV derived from Aag2 cells clustered into one clade but were far from those isolated or identified from Ae. aegypti. Aag2-derived CFAV efficiently replicated in the mosquito body and did not attenuate the survival of Ae. aegypti. However, the viral load in the ovarian tissues was much lower than that in other tissues and the virus could not passage to the offspring by vertical transmission. CONCLUSIONS: The results of this study demonstrate that Aag2-derived CFAV was not vertically transmitted in Ae. aegypti and provide valuable information on the colonization of mosquitoes by this virus.

Potential Global Distribution of the Invasive Mosquito Aedes koreicus under a Changing Climate.

Invasive alien species are a growing threat to natural systems, the economy, and human health. Active surveillance and responses that readily suppress newly established colonies are effective actions to mitigate the noxious consequences of biological invasions. Aedes (Hulecoeteomyia) koreicus (Edwards), a mosquito species native to East Asia, has spread to parts of Europe and Central Asia since 2008. In the last decade, Ae. koreicus has been shown to be a competent vector for chikungunya virus and Dirofilaria immitis. However, information about the current and potential distribution of Ae. koreicus is limited. Therefore, to understand the changes in their global distribution and to contribute to the monitoring and control of Ae. koreicus, in this study, the MaxEnt model was used to predict and analyze the current suitable distribution area of Ae. koreicus in the world to provide effective information.

Estimating Venous Thromboembolism Risk in Metastatic Colorectal Cancer Inpatients: Validation of Existing Risk Scores and Development of New Risk Scores.

Metastatic colorectal cancer (mCRC) patients are predisposed to venous thromboembolism (VTE). This study aimed to (1) evaluate the efficacy of 4 existing cancer-specific VTE models in predicting VTE incidence among hospitalized mCRC patients, and (2) examine the influence of incorporating mCRC molecular subtypes into these models. We conducted an evaluation of 4 cancer-specific VTE models, including Khorana, Vienna CATS, Protecht, and CONKO in a dataset involving 1392 mCRC patients. To evaluate the predictive performance, we utilized receiver operating characteristic (ROC) curves for both the original models and the modified models that incorporated microsatellite instability status or KRAS/NRAS/BRAF mutations. Moreover, we computed the net reclassification improvement (NRI) to quantify the enhancements made to the modified VTE risk models. All models demonstrated a moderate area under the ROC curve (ROC-AUC) when predicting the occurrence of VTE: Khorana (0.550), Vienna CATS (0.671), Protecht (0.652), and CONKO (0.578). The incorporation of KRAS and BRAF mutations significantly improved the ROC-AUC of all 4 existing models (modified Khorana: 0.796, modified Vienna CATS: 0.832, modified Protecht: 0.834, and modified CONKO: 0.809). After dichotomizing the risk using a threshold of 3 points and comparing them with the original models, NRI values for the 4 modified models were 0.97, 0.95, 1.11, and 0.98, respectively. All 4 cancer-specific VTE models exhibit moderate performance when identifying mCRC patients at high risk of VTE. Incorporating KRAS and BRAF mutations may enhance the prediction of VTE in hospitalized mCRC patients.

The predicted potential distribution of Aedes albopictus in China under the shared socioeconomic pathway (SSP)1-2.6.

Aedes albopictus (Skuse) (Diptera: Culicidae) is one of the 100 most invasive species in the world and represents a significant threat to public health. The distribution of Ae. albopictus has been expanding rapidly due to increased international trade, population movement, global warming and accelerated urbanization. Consequently, it is very important to know the potential distribution area of Ae. albopictus in advance for early warning and control of its spread and invasion. We randomly selected 282 distribution sites from 27 provincial-level administrative regions in China, and used the GARP and MaxEnt models to analyze and predict the current and future distribution areas of Ae. albopictus in China. The results showed that the current range of Ae. albopictus in China covers most provinces such as Yunnan and Guizhou Provinces, and the distribution of Ae. albopictus in border provinces such as Tibet, Gansu and Jilin Provinces tend to expand westwards. In addition, the potential distribution area of Ae. albopictus in China will continue to expand westwards due to future climate change under the SSP126 climate scenario. Furthermore, the results of environmental factor filtering showed that temperature and precipitation had a large effect on the distribution probability of Ae. albopictus.

Characterization and Antibacterial Properties of Egg White Protein Films Loaded with ε-Polylysine: Evaluation of Their Degradability and Application.

There is an ongoing trend to design new kinds of food packaging materials with excellent properties which are environmentally friendly enough. The aim of this study was to prepare and characterize egg white protein (EWP)-based composite films with and without ε-polylysine (Lys), as well as to compare their physical-chemical properties, structural properties, degradation and antibacterial properties. The results showed that with the addition of Lys, the composite films showed a decreasing tendency of the water permeability due to the enhanced interaction between proteins and water molecules. As indicated by the structural properties, stronger cross-linking and intermolecular interactions happened with increasing concentration of Lys. In addition, the composite films presented excellent antibacterial activities against Escherichia coli and Staphylococcus aureus on chilled pork in the presence of Lys. Therefore, our prepared films might be used as a freshness-keeping material with an application in meat preservation. The biodegradation evaluation demonstrated that the composite films were environmental-friendly and have potential applications in the field of food packaging.

lncRNA SYTL5-OT4 promotes vessel co-option by inhibiting the autophagic degradation of ASCT2.

AIMS: Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance. METHODS: SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays. The effects of SYTL5-OT4 and ASCT2 on tumor cells were investigated by gain- and loss-of-function experiments, and those of SYTL5-OT4 on ASCT2 expression were analyzed by RNA immunoprecipitation and co-immunoprecipitation assays. The roles of SYTL5-OT4 and ASCT2 in vessel co-option were detected by histological, immunohistochemical, and immunofluorescence analyses. RESULTS: The expression of SYTL5-OT4 and ASCT2 was higher in patients with AAT-resistant CRCLM. SYTL5-OT4 enhanced the expression of ASCT2 by inhibiting its autophagic degradation. SYTL5-OT4 and ASCT2 promoted vessel co-option by increasing the proliferation and epithelial-mesenchymal transition of tumor cells. Combination therapy of ASCT2 inhibitor and antiangiogenic agents overcame vessel co-option-mediated AAT resistance in CRCLM. CONCLUSION: This study highlights the crucial roles of lncRNA and glutamine metabolism in vessel co-option and provides a potential therapeutic strategy for patients with AAT-resistant CRCLM.

Photo-Activated Circularly Polarized Luminescence Film Based on Aggregation-Induced Emission Copper(I) Cluster-Assembled Materials.

In this study, a pair of chiral copper(I) cluster-assembled materials (R/S-2) was prepared, exhibiting unique photo-response characteristics with a concentration-wavelength correlation property in DMSO solution. By the combination of R/S-2 with a polymethyl methacrylate (PMMA) matrix, the first photo-activated circularly polarized luminescence (CPL) film was developed, the CPL signal (glum =9×10-3 ) of which could be induced by UV light irradiation. Moreover, the film exhibited a reversible photo-response and extremely good fatigue resistance. Mechanism study revealed that the photo-response properties of the R/S-2 solution and film are attributed to the aggregation-induced emission (AIE) characteristics of R/S-2 and a photo-induced deoxygenation process. This study enriches the types of luminescent cluster-assembled molecules and provides a new strategy for the construction of metal cluster-based stimuli-responsive composite materials.

Development and validation of machine learning models for postoperative venous thromboembolism prediction in colorectal cancer inpatients: a retrospective study.

Background: Colorectal cancer (CRC) is a heterogeneous group of malignancies distinguished by distinct clinical features. The association of these features with venous thromboembolism (VTE) is yet to be clarified. Machine learning (ML) models are well suited to improve VTE prediction in CRC due to their ability to receive the characteristics of a large number of features and understand the dataset to obtain implicit correlations. Methods: Data were extracted from 4,914 patients with colorectal cancer between August 2019 and August 2022, and 1,191 patients who underwent surgery on the primary tumor site with curative intent were included. The variables analyzed included patient-level factors, cancer-level factors, and laboratory test results. Model training was conducted on 30% of the dataset using a ten-fold cross-validation method and model validation was performed using the total dataset. The primary outcome was VTE occurrence in postoperative 30 days. Six ML algorithms, including logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), weighted support vector machine (SVM), a multilayer perception (MLP) network, and a long short-term memory (LSTM) network, were applied for model fitting. The model evaluation was based on six indicators, including receiver operating characteristic curve-area under the curve (ROC-AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Brier score. Two previous VTE models (Caprini and Khorana) were used as the benchmarks. Results: The incidence of postoperative VTE was 10.8%. The top ten significant predictors included lymph node metastasis, C-reactive protein, tumor grade, anemia, primary tumor location, sex, age, D-dimer level, thrombin time, and tumor stage. In our results, the XGBoost model showed the best performance, with a ROC-AUC of 0.990, a SEN of 96.9%, a SPE of 96.1% in training dataset and a ROC-AUC of 0.908, a SEN of 77.5%, a SPE of 93.7% in validation dataset. All ML models outperformed the previously developed models (Caprini and Khorana). Conclusions: This study developed postoperative VTE predictive models using six ML algorithms. The XGBoost VTE model might supply a complementary tool for clinical VTE prophylaxis decision-making and the proposed risk factors could shed some light on VTE risk stratification in CRC patients.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.