Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Association of education with cholelithiasis and mediating effects of cardiometabolic factors: A Mendelian randomization study.

BACKGROUND: Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated. AIM: To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations. METHODS: Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; n = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis. RESULTS: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses. CONCLUSION: Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure.

Accuracy and efficiency of dynamic navigated root-end resection in endodontic surgery: a pilot in vitro study.

BACKGROUND: The operation accuracy and efficiency of dynamic navigated endodontic surgery were evaluated through in vitro experiments. This study provides a reference for future clinical application of dynamic navigation systems in endodontic surgery. MATERIALS AND METHODS: 3D-printed maxillary anterior teeth were used in the preparation of models for endodontic surgery. Endodontic surgery was performed with and without dynamic navigation by an operator who was proficient in dynamic navigation technology but had no experience in endodontic surgery. Optical scanning data were applied to evaluate the length and angle deviations of root-end resection. And the operation time was recorded. T tests were used to analyze the effect of dynamic navigation technology on the accuracy and duration of endodontic surgery. RESULTS: With dynamic navigation, the root-end resection length deviation was 0.46 ± 0.06 mm, the angle deviation was 2.45 ± 0.96°, and the operation time was 187 ± 22.97 s. Without dynamic navigation, the root-end resection length deviation was 1.20 ± 0.92 mm, the angle deviation was 16.20 ± 9.59°, and the operation time was 247 ± 61.47 s. Less deviation was achieved and less operation time was spent with than without dynamic navigation (P < 0.01). CONCLUSION: The application of a dynamic navigation system in endodontic surgery can improve the accuracy and efficiency significantly for operators without surgical experience and reduce the operation time.

The role of fungi in the diagnosis of colorectal cancer.

Colorectal cancer (CRC) is a prevalent tumour with high morbidity rates worldwide, and its incidence among younger populations is rising. Early diagnosis of CRC can help control the associated mortality. Fungi are common microorganisms in nature. Recent studies have shown that fungi may have a similar association with tumours as bacteria do. As an increasing number of tumour-associated fungi are discovered, this provides new ideas for the diagnosis and prognosis of tumours. The relationship between fungi and colorectal tumours has also been recently identified by scientists. Therefore, this paper describes the limitations and prospects of the application of fungi in diagnosing CRC and predicting CRC prognosis.

Use of 3D Echocardiography Facilitates Analysis of Thrombolytic Efficacy in Patients With Persistent Atrial Fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.

Platelet Concentrates Preconditioning of Mesenchymal Stem Cells and Combined Therapies: Integrating Regenerative Strategies for Enhanced Clinical Applications.

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs' composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.

Synergistic Radiation Effects in PPD CMOS Image Sensors Induced by Neutron Displacement Damage and Gamma Ionization Damage.

The synergistic effects on the 0.18 µm PPD CISs induced by neutron displacement damage and gamma ionization damage are investigated. The typical characterizations of the CISs induced by the neutron displacement damage and gamma ionization damage are presented separately. The CISs are irradiated by reactor neutron beams up to 1 × 1011 n/cm2 (1 MeV neutron equivalent fluence) and 60Co γ-rays up to the total ionizing dose level of 200 krad(Si) with different sequential order. The experimental results show that the mean dark signal increase in the CISs induced by reactor neutron radiation has not been influenced by previous 60Co γ-ray radiation. However, the mean dark signal increase in the CISs induced by 60Co γ-ray radiation has been remarkably influenced by previous reactor neutron radiation. The synergistic effects on the PPD CISs are discussed by combining the experimental results and the TCAD simulation results of radiation damage.

Escherichia coli-Induced cGLIS3-Mediated Stress Granules Activate the NF-κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression.

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

[Effects of Conservation Tillage on Herbicide Residues in Maize Field Soil].

It is well known that conservation tillage can improve soil quality, such as soil organic matters. However, limited information on the conservation tillage impacts on pesticides has been reported, which is important to food security. To explore the specific effects of conservation tillage on herbicide residues in soils, parallel soil samples from seven sites under traditional tillage and conservation tillage were collected, respectively, in Jilin Province, Northeast China. The soil properties and characteristics of three herbicides(acetochlor, atrazine, and MCPA-Na) were measured. The results showed that conservation tillage significantly increased total organic carbon(TOC) content, soil water content, and the average particle size of soil aggregates[(2.1±0.1)%, (19.1±1.2)%, and (82.2±3.0) µm increased to(2.9±0.3)%, (22.3±1.5)%, and (97.2±4.2) µm, respectively]. The results also showed that different herbicides were correlated with different soil properties. For example, TOC content and soil water content were positively correlated with atrazine, whereas micro-aggregate content was negatively correlated with acetochlor. Therefore, the effects of conservation tillage on the three herbicide residues were different. For instance, conservation tillage significantly increased the residual amount of atrazine[from(3.8±0.3) ng·g-1 to (17.7±3.0) ng·g-1] in the Dongfeng site by increasing TOC content, whereas it significantly reduced the residual amount of acetochlor[from (50.6±10.3) ng·g-1 to (9.2±2.5) ng·g-1] in the Dehui site by increasing the average particle size of soil aggregates. Generally, this study suggests conservation tillage indeed affected herbicide residues in soils by affecting soil properties. However, the influence of conservation tillage on herbicide residue was dependent on the types of herbicides due to the complex effects of different soil properties on herbicide migration and degradation.

A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.

[Cuproptosis-related lncRNAs to predict biochemical recurrence of prostate cancer].

OBJECTIVE: To construct a cuproptosis-related lncRNA model and obtain some new ideas and methods for predicting the biochemical recurrence (BCR) of PCa. METHODS: We identified cuproptosis-related lncRNAs from the gene expression data, mutation load data and clinical data on PCa patients in the Cancer Genome Atlas (TCGA) database and divided the patients into a training group and a verification group. We constructed a prognostic risk scoring model based on the cuproptosis -related lncRNAs, verified the validity of the model by BCR-free survival analysis, logistic regression analysis and independent prognosis analysis, and visualized the results using ROC curve analysis, Kaplan-Meier survival curves and the correlation heat map. We performed differential analysis and survival analysis of the tumor mutation burden (TMB), and assessed the value of the model and TMB in predicting the BCR of PCa. RESULTS: A prognostic risk scoring model was successfully constructed based on the 6 cuproptosis -related lncRNAs identified from the PCa cases in the training group, which were divided into a high- and a low-risk groups according to the median value. The incidence of BCR rose with the increase of the risk score, and the BCR-free time was significantly shorter in the high-risk group (P < 0.05). The model also exhibited a high differentiation value in different age groups (P < 0.05), which was shown to be a reliable and independent prognostic indicator for predicting the BCR of PCa, even more valuable than other clinicopathological indicators. TMB was differentially expressed in the high- and low-risk groups (P < 0.01) and significantly correlated with BCR. The highest rate of BCR-free survival was found in the patients with low risk scores and low TMB (P < 0.01). CONCLUSION: A cuproptosis -related lncRNA model was successfully constructed, which can accurately predict the risk of BCR in PCa patients. The higher the prognostic risk score, the greater the possibility of BCR. TMB is high in patients with a high risk, and the TMB level has certain suggestive significance for BCR.

[Effect of bird-induced anus-lifting surgery combined with oral Relinqing Granules on LUTS/CP with damp heat syndrome: Evaluation by infrared thermal imaging].

OBJECTIVE: To observe the clinical effect of bird-induced anus-lifting surgery (BIAL) combined with oral Relinqing Granules (RG) in the treatment of lower urinary tract symptoms / chronic prostatitis (LUTS/CP) with damp-heat syndrome using infrared thermal imaging (ITI). METHODS: This study included 165 cases of LUTS/CP with damp-heat syndrome treated in the Departments of Andrology and Urology of our hospital, which were divided into three groups of an equal number and treated by medication of oral tamsulosin hydrochloride at 0.2 mg, qd plus levofloxacin at 0.2 g bid (control), anus-lifting exercise (15 lifts once a day) combined with oral RG at 8 g tid (routine treatment) and BIAL (15 lifts once a day) combined with oral RG at 8 g tid (BIAL+RG), respectively, all for two weeks. We recorded the ITI indicators, NIH-CPSI and Self-Rating Anxiety Scale (SAS) scores of patients before and after treatment, observed adverse reactions during the treatment, and compared them among the three groups of patients. RESULTS: Compared with the baseline, NIH-CPSI and SAS scores were significantly reduced in all the three groups after treatment (P < 0.05), even more significantly in the BIAL+RG (10.49 ± 2.97 and 49.73 ± 2.79) than in the control (21.15 ± 3.56 and 52.62 ± 5.38) and routine treatment groups (15.55 ± 2.77 and 52.35 ± 3.87) (P < 0.05). The ITI temperature at the related parts of the body was remarkably decreased in the three groups after treatment (P < 0.05), even lower in the BIAL+RG group (30.47 ± 1.61, 32.14 ± 1.25, 31.16 ± 1.58, 31.97 ± 1.19) than in the control (33.39 ± 0.6, 33.64 ± 1.07, 32.78 ± 0.58, 33.18 ± 0.78) and routine treatment groups (31.93 ± 1.14, 33.06 ± 0.8, 33.08 ± 0.82, 33.17 ± 1.05) (P < 0.05), with statistically significant difference from the baseline in the BIAL+RG group after 12 hours and 24 hours of treatment (ï¼»34.26 ± 0.06ï¼½ vs ï¼»32.65 ± 0.05ï¼½ and ï¼»32.72 ± 0.09ï¼½, P < 0.05), but not between the two time points (P > 0.05). The incidence rate of adverse reactions was markedly lower in the BIAL+RG and routine treatment groups than in the control (P < 0.05) but not significantly different between the BIAL+RG and routine treatment groups (P > 0.05). CONCLUSION: Bird-induced anus-lifting surgery combined with oral Relinqing Granules can safely and significantly improve infrared thermal imaging indicators and NIH-CPSI scores in LUTS/CP patients with damp-heat syndrome.

The characteristics of particulate matter in different subway station environmental control systems.

Particulate matter (PM2.5, PM10) in urban subway stations can significantly impact passengers' health. The particle concentration in subway stations is influenced by many factors. However, few existing studies have explored the impact of environmental control systems in-depth, especially under different outdoor pollution conditions. To address this research gap, this study focused on measuring and comparing the characteristics of PM2.5 and PM10 at subway stations with three control systems (open, closed, and screen door) under varying pollution conditions in Beijing. Particle concentrations from platforms, carriages, and outdoors were monitored and analyzed using statistical methods. The results showed that the particle concentration in the closed system was generally 20-40 µg/m3 higher than that in the screen system at the platform, which might be attributed to the piston wind, as the air from the tunnel with a lot of dirt. The pollution in the carriage was more severe for the open system than that of the screen system. The PM2.5/PM10 ratio in the carriage was 91%, 90%, and 83.84% for the closed, open, and screen systems, respectively. This indicates that the screen door could reduce the particle concentration in the platform to 10%-50%. The particle concentration varied among subway stations with different environmental control systems, suggesting that the prevention and control strategies for particulate matter pollution should be different for stations with different systems.

Clinical Outcome and Predictors of Endodontic Microsurgery Using Cone-beam Computed Tomography: A Retrospective Cohort Study.

INTRODUCTION: The aim of this retrospective cohort study was to evaluate the clinical outcomes and identify the prognostic factors of endodontic microsurgery based on cone-beam computed tomographic (CBCT) scans. METHODS: Patients who underwent endodontic microsurgery in teeth with asymptomatic apical periodontitis were included. The clinical outcomes were determined based on clinical and radiographic examinations after surgery 12-48 months. Radiographic healing was assessed on CBCT images by using the modified PENN 3-dimensional criteria and classified into 4 categories: complete, limited, uncertain, and unsatisfactory healing. Multivariate logistic regression was performed to detect outcome risk factors. RESULTS: Of the 204 teeth in 173 invited patients, 148 teeth of 126 patients were examined at review. On CBCT images, 88 teeth (59.5%) showed complete healing, and 42 (28.4%) teeth showed limited healing. All these 130 teeth were asymptomatic and achieved a clinical success rate of 87.8%. Uncertain healing was observed in 9 teeth, one of which was symptomatic. The remaining 9 teeth were unsatisfactory healing on CBCT scans, including 6 teeth with clinical symptoms and 3 free. Lesion type and root-end filling quality were significant outcome predictors (P < .05). The risk of treatment failure for teeth with combined endodontic-periodontal lesions was 8.6 times higher than that for teeth with isolated endodontic lesions. Adequate root-end filling quality improved the probability of success by 5.3 times. CONCLUSIONS: Based on CBCT data, an adequate performed endodontic microsurgery could have predictable success in teeth without periodontal involvement.

What affects China's green finance? Evidence from cryptocurrency market, oil market, and economic policy uncertainty.

This paper discusses the dynamic long- and short-term effects of bitcoin price (BTP), crude oil price (COP), and uncertainty of economic policy (EPU) on China's green bond (CGB) market, separately. Depending on the quantile autoregressive distributed lag method, the empirical results are shown that BTP and EPU exert substantial positive and negative effects on the CGB market in the long term for most circumstances, while their effects reflect not prominent in the short term. The main contributions can be summarized as follows. Given that China is the largest bitcoin mining state and a major green bond issuer, this study first explores the linkages between them. Furthermore, both long- and short-term effects are investigated from BTP, COP, and EPU to CGB, and long-term effects are dominated in the interrelationships among variables, indicating that the CGB market is mainly driven by permanent shocks. In addition, the mentioned long-term effects are deeply discussed from time- and quantile-varying aspects. This approach considers diverse situations in the bond market and various incidents that occur at various durations of time. The results underscore the significance of market participants gaining a deeper comprehension of how BTP, COP, and EPU impact green bond within varying market conditions. Implementing specific policies, such as establishing a cohesive and efficient bond market and making careful adjustments to economic policies, can be advantageous in maintaining stability within the CGB market.

Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. METHODS: The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. RESULTS: We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. CONCLUSIONS: This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.

Incidence of post-stroke cognitive impairment in patients with first-ever ischemic stroke: a multicenter cross-sectional study in China.

Background: Post-stroke cognitive impairment (PSCI) is a common sequela after stroke. China has a large population of stroke survivors, but a large-scale survey on the incidence and risk factors for PSCI has not been undertaken. We aimed to calculate the incidence and risk factors for vascular cognitive symptoms among first-ever stroke survivors in China through a multicenter cross-sectional study. Methods: From May 1, 2019 to November 30, 2019, patients with a clinical diagnosis of first-ever ischemic stroke were recruited from 563 hospitalized-based stroke center networks in 30 provinces of China. Cognitive impairment was measured by 5-min National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) at 3-6 months after the indexed stroke. Stepwise multivariate regression and stratified analysis were performed to assess the association between PSCI and demographic variables. Findings: A total of 24,055 first-ever ischemic stroke patients were enrolled, with an average age of 70.25 ± 9.88 years. The incidence of PSCI as per the 5-min NINDS-CSN was 78.7%. Age ≥75 years old (OR: 1.887, 95%CI: 1.391-2.559), western regional residence (OR: 1.620, 95%CI: 1.411-1.860) and lower education level were associated with increased PSCI risk. Hypertension might be related to non-PSCI (OR: 0.832, 95%CI: 0.779-0.888). For patients under 45 years old, unemployment was an independent risk factor for PSCI (OR: 6.097, 95%CI: 1.385-26.830). For patients who were residents of the southern region (OR: 1.490, 95%CI: 1.185-1.873) and non-manual workers (OR: 2.122, 95%CI: 1.188-3.792), diabetes was related to PSCI. Interpretation: PSCI is common in Chinese patients with first-ever stroke, and many risk factors are related to the occurrence of PSCI. Funding: The Beijing Hospitals Authority Youth Program (No. QMS20200801); Youth Program of the National Natural Science Foundation of China (No. 81801142); the Key Project of Science and Technology Development of China Railway Corporation (No. K2019Z005); The Capital Health Research and Development of Special (No. 2020-2-2014); Science and Technology Innovation 2030-Major Project (No. 2021ZD0201806).

Comparative Analysis of Codon Usage Patterns in Nuclear and Chloroplast Genome of Dalbergia (Fabaceae).

The Dalbergia plants are widely distributed across more than 130 tropical and subtropical countries and have significant economic and medicinal value. Codon usage bias (CUB) is a critical feature for studying gene function and evolution, which can provide a better understanding of biological gene regulation. In this study, we comprehensively analyzed the CUB patterns of the nuclear genome, chloroplast genome, and gene expression, as well as systematic evolution of Dalbergia species. Our results showed that the synonymous and optimal codons in the coding regions of both nuclear and chloroplast genome of Dalbergia preferred ending with A/U at the third codon base. Natural selection was the primary factor affecting the CUB features. Furthermore, in highly expressed genes of Dalbergia odorifera, we found that genes with stronger CUB exhibited higher expression levels, and these highly expressed genes tended to favor the use of G/C-ending codons. In addition, the branching patterns of the protein-coding sequences and the chloroplast genome sequences were very similar in the systematic tree, and different with the cluster from the CUB of the chloroplast genome. This study highlights the CUB patterns and features of Dalbergia species in different genomes, explores the correlation between CUB preferences and gene expression, and further investigates the systematic evolution of Dalbergia, providing new insights into codon biology and the evolution of Dalbergia plants.