Disease burden of stroke and its subtypes attributable to low dietary fiber in China, 1990-2019.

This study aimed to assess the current status and changing trends of the disease burden of stroke and its subtypes due to low dietary fiber intake in China from 1990 to 2019. In cases of stroke and its subtypes attributable to low dietary fiber, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMR), age-standardized DALYs rates (ASDR), and percentage change were used to assess disease burden. Data were obtained from the 2019 global burden of disease study. Trends were assessed using Joinpoint regression and age-period-cohort analysis. Between 1990 and 2019, there was a declining trend in stroke and its subtypes, ASDR and ASMR, as well as the corresponding number of deaths and DALYs, due to low dietary fiber intake in China. Subarachnoid hemorrhage (SH) showed the greatest decrease, followed by intracerebral hemorrhage (IH) and ischemic stroke (IS). Local drift curves showed a U-shaped distribution of stroke, IS, and IH DALYs across the whole group and sex-based groups. For mortality, the overall and male trends were similar to those for DALYs, whereas female stroke, IH, and IS showed an upward trend. The DALYs for stroke and IH showed a clear bimodal distribution, IS showed an increasing risk with age. For mortality, the SH subtype showed a decreasing trend, whereas other subtypes showed an increasing risk with age. Both the period and cohort rates of stroke DALYs and motality due to low dietary fiber have declined. Males had a higher risk of DALYs and mortality associated with low fiber levels. The burden of stroke and its subtypes associated with a low-fiber diet in China has been declining over the past 30 years, with different patterns of change for different stroke subtypes and a higher burden for males, highlighting the differential impact of fiber intake on stroke and its subtypes.

Short-term exposure to triclocarban alters microbial community composition and metabolite profiles in freshwater biofilms.

Triclocarban (TCC), an emerging contaminant in water environments, its effects on freshwater biofilms remain insufficiently understood. This study investigates the effects of TCC exposure (at concentrations of 10 µg L-1 and 10 mg L-1) on mature freshwater biofilms. TCC was found to inhibit biofilm activity as evidenced by changes in surface morphology and the ratio of live/dead cells. Moreover, both concentrations of TCC were observed to modify the structure of the biofilm community. Metabolomics analysis revealed an overlap in the toxicity mechanisms and detoxification strategies triggered by various concentrations of TCC in biofilms. However, the higher toxicity induced by 10 mg L-1 TCC resulted from the downregulation of proline betaine, disrupting the homeostasis of cellular osmotic pressure regulation in biofilms. Notably, lipid and lipid-like molecules showed high sensitivity to different concentrations of TCC, indicating their potential as biomarkers for TCC exposure. Annotation of the differential metabolites by KEGG revealed that alterations in amino acid and carbon metabolism constituted the primary response mechanisms of biofilms to TCC. Moreover, the biofilm demonstrated enhanced nucleic acid metabolism, which bolstered resistance against TCC stress and heightened tolerance. Furthermore, elevated TCC concentrations prompted more robust detoxification processes for self-defense. Overall, short-term exposure to TCC induced acute toxicity in biofilms, yet they managed to regulate their community structure and metabolic levels to uphold oxidative homeostasis and activity. This research contributes to a deeper comprehension of TCC risk assessment and policy control in aquatic environments.

Burden of ischemic stroke attributable to a high red meat diet in China, 1990-2019: analysis based on the 2019 Global Burden of Disease Study.

Background: The burden of ischemic stroke (IS) linked to high consumption of red meat is on the rise. This study aimed to analyze the mortality and disability-adjusted life years (DALYs) trends for IS attributed to high red meat intake in China between 1990 and 2019 and to compare these trends with global trends. Methods: This study extracted data on IS attributed to diets high in red meat in China from 1990 to 2019 from the Global Burden of Disease Study (GBD) database. Key measures, including mortality, DALYs, age-standardized mortality rates (ASMR), and age-standardized DALYs rates (ASDR), were used to estimate the disease burden. The estimated annual percentage change and joinpoint regression models were employed to assess the trends over time. An age-period-cohort analysis was used to assess the contribution of a diet high in red meat to the age, period, and cohort effects of IS ASMR and ASDR. Results: Between 1990 and 2019, deaths and DALYs from IS attributed to a diet high in red meat in China, along with corresponding age-standardized rates, significantly increased. The overall estimated annual percentage change for the total population and across sex categories ranged from 1.01 to 2.08. The average annual percentage changes for overall ASDR and ASMR were 1.4 and 1.33, respectively, with male ASDR and ASMR average annual percentage changes at 1.69 and 1.69, respectively. Contrastingly, female ASDR and ASMR average annual percentage changes were 1.07 and 0.87, respectively. Except for a few periods of significant decrease in females, all other periods indicated a significant increase or nonsignificant changes. Incidence of IS linked to a diet high in red meat rose sharply with age, displaying increasing period and cohort effects in ASDR. Female ASMR period and cohort effect ratios initially increased and then decreased, whereas the male ratio showed an upward trend. Conclusion: This study comprehensively analyzed epidemiological characteristics that indicated a marked increase in mortality and DALYs from IS attributable to high red meat consumption, contrasting with a global downtrend. This increase was more pronounced in males than females. This research provides valuable insights for enhancing IS prevention in China.

Pro-CRISPR PcrIIC1-associated Cas9 system for enhanced bacterial immunity.

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.

Predict nutrition-related adverse outcomes in head and neck cancer patients undergoing radiotherapy: A systematic review.

BACKGROUND: Acute nutrition-related adverse outcomes are common in head and neck cancer patients undergoing radiotherapy. Predictive models can assist in identifying high-risk patients to enable targeted intervention. We aimed to systematically evaluate predictive models for predicting severe acute nutritional symptoms, insufficient intake, tube feeding, sarcopenia, and weight loss. METHODS: We searched PubMed, Web of Science, EBSCO, Embase, WanFang, CNKI, and SinoMed. We selected studies developing predictive models for the aforementioned outcomes. Data were extracted using a predefined checklist. Risk of bias and applicability assessment were assessed using the Prediction model Risk of Bias Assessment Tool. A narrative synthesis was conducted to summarize the model characteristics, risk of bias, and performance. RESULTS: A total of 2941 studies were retrieved and 19 were included. Study outcome measure were different symptoms (n = 11), weight loss (n = 5), tube feeding (n = 3), and symptom or tube feeding (n = 1). Predictive factors mainly encompassed sociodemographic data, disease-related data, and treatment-related data. Seventeen studies reported area under the curve or C-index values ranging from 0.610 to 0.96, indicating moderate to good predictive performance. However, candidate predictors were incomplete, outcome measures were diverse, and the risk of bias was high. Most of them used traditional model development methods, and only two used machine learning. CONCLUSIONS: Most current models showed moderate to good predictive performance. However, predictors are incomplete, outcome are inconsistent, and the risk of bias is high. Clinicians could carefully select the models with better model performance from the available models according to their actual conditions. Future research should include comprehensive and modifiable indicators and prioritize well-designed and reported studies for model development.

Construction and validation of a risk-prediction model for chemotherapy-related cognitive impairment in patients with breast cancer.

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage.

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

Nicorandil Regulates Ferroptosis and Mitigates Septic Cardiomyopathy via TLR4/SLC7A11 Signaling Pathway.

This study mainly explored the role of nicorandil in regulating ferroptosis and alleviating septic cardiomyopathy through toll-like receptor (TLR) 4/solute carrier family 7 member 11 (SLC7A11) signaling pathway. Twenty-four male SD rats were randomly divided into control, Nic (nicorandil), LPS (lipopolysaccharide), and LPS + Nic groups and given echocardiography. A detection kit was applied to measure the levels of lactic dehydrogenase (LDH), cardiac troponin I (cTnI), and creatine kinase-MB (CK-MB); HE staining and the levels of glutathione (GSH), malondialdehyde (MDA), total iron, and Fe2+ of myocardial tissues were detected. Moreover, the expression of TLR4 and SLC7A11 were measured by qRT-PCR and the proteins regulating ferroptosis (TLR4, SLC7A11, GPX4, ACSL4, DMT1, Fpn, and TfR1) were checked by western blot. Myocardial cells (H9C2) were induced with lipopolysaccharide (LPS) and transfected with si-TLR4 or SLC7A11-OE. Then, the viability, ferroptosis, and TLR4/SLC7A11 signaling pathway of cells were examined. Nicorandil could significantly increase left ventricular (LV) ejection fraction (LVEF) while reduce LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV). Also, it greatly reduced the levels of LDH, cTnI, and CK-MB; alleviated the pathological changes of myocardial injury; notably decreased MDA, total iron, and Fe2+ levels in myocardial tissues; and significantly increased GSH level. Besides, nicorandil obviously raised protein levels of GPX4, Fpn, and SLC7A11, and decreased protein levels of ACSL4, DMT1, TfR1, and TLR4. After knockdown of TLR4 or overexpression of SLC7A11, the inhibition effect of nicorandil on ferroptosis was strengthened in LPS-induced H9C2 cells. Therefore, nicorandil may regulate ferroptosis through TLR4/SLC7A11 signaling, thereby alleviating septic cardiomyopathy.

Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis.

BACKGROUND: The migration of lymphocytes shares many similarities in mode and mechanism with the metastasis of lung cancer tumor cells. But changes in the expression of lymphocyte migration regulation related proteins in urine exosomes remain unclear. This study is to investigate the expression changes of lymphocyte migration regulation related proteins in urine exosomes of lung cancer patients, and further verify their correlation with the development and progression of lung cancer. METHODS: Urine exosomes were collected from lung cancer patients and healthy people aged 15-79 years. Mass spectrometry was used to screen and explore the expression changes of lymphocyte migration regulation related proteins in healthy people of different ages. Enzyme-linked immunosorbent assay and western blotting were used to detect the expression changes of lymphocyte migration regulation related proteins in lung cancer patients. RESULTS: Analyzing the data of urine exosome proteomics, a total of 12 lymphocyte related proteins were identified, 5 of which were lymphocyte migration regulation related proteins. Among these proteins, WASL and STK10 proteins showed a gradual decrease in expression with age, and WNK1 protein showed a gradual increase. Lung cancer patients had reduced expression of WASL and increased expression of STK10 and WNK1 proteins in urine exosomes compared to normal people. Urine exosome WASL, STK10, and WNK1 were diagnosed with lung cancer, with a combined AUC of 0.760. CONCLUSIONS: Lymphocyte migration regulation related proteins were differentially expressed in the urine exosome of lung cancer patients, and WASL, STK10 and WNK1 may serve as potential biomarkers for lung cancer diagnosis.

Comparison of prognosis after partial and total surgical resection for parathyroid carcinoma: an inverse probability of treatment weighting analysis of the SEER database.

Background: Complete resection of the tumor and the ipsilateral thyroid lobe at the primary surgery is the "gold standard" for the treatment of parathyroid carcinoma (PC). However, differences in the overall survival (OS) of patients with PC who underwent partial and total surgical resection remain to be determined. Methods: Data on patients with PC who underwent partial and total surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database (2000-2018). The X-tile software (https://medicine.yale.edu/lab/rimm/research/software/) was used to define the optimal cut-off values for continuous variables. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare the OS of patients with PC in the partial and total surgical resection groups. Results: A total of 334 patients with PC were included in this study (183 and 151 in the partial and total surgical resection groups, respectively). The optimal cut-off values for age at diagnosis were 53 and 73 years, respectively, while that for tumor size was 34 mm. In both the Kaplan-Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, the difference in OS between the partial and total surgical resection groups was not statistically significant (p>0.05). These findings were confirmed in the IPTW-adjusted Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis (p>0.05). Subgroup analysis revealed that total surgical resection was beneficial for OS only in the subgroup with unknown tumor size. Conclusion: There was no significant difference in the prognosis of patients who underwent partial and total surgical resection. This finding may provide a useful reference for the treatment of PC.

Thyroid cancer burden and risk factors in China from 1990-2019: a systematic analysis using the global burden of disease study.

Background: Thyroid cancer (TC) is the most common endocrine system malignancy with a rapidly increasing incidence in China. Epidemiological data on TC at the national level are lacking. This study aimed to quantify the TC disease burden in China between 1990 and 2019 and evaluate the current status and trends of the disease burden attributed to a high body mass index (HBMI). Methods: The 2019 Global Burden of Disease Study dataset was used to explore the TC disease burden. Age-standardized rates of incidence (ASIR), prevalence (ASPR), deaths (ASDR), and disability-adjusted life years (DALYs) were considered and the estimated annual percentage change (EAPC) was calculated as a measure of the average change in age-standardized rates. The trend in TC-related mortality and DALYs attributed to an HBMI, accounting for different age groups and sexes, was examined. Results: Between 1990 and 2019, the ASDR and DALYs for TC decreased by 0.02/100000 and 1.17/100000, respectively. The ASPR and ASIR increased by 9.88/100000 and 1.04/100000, respectively. The EAPC for ASDR, age-standardized rates of DALYs, ASPR, and ASIR were 0.06 (95% CI: -0.09, 0.21), -0.20 (95% CI: -0.31, -0.10), 3.52 (95% CI: 3.35, 3.68), and 2.73 (95% CI: 2.58, 2.88), respectively. TC-related deaths, DALYs, and their prevalence and incidence in China increased by 118%, 350%, 81%, and 290%, respectively. The disease burden of TC was higher among male than female patients in different age groups, with varying distributions. The disease burden attributed to HBMI gradually increased over the past 30 years according to age-standardized DALYs, particularly in male patients. Conclusion: The TC burden has increased in China over the past 30 years, and population aging poses a challenge to TC prevention and control. HBMI has become an important factor in the TC disease burden and further research should focus on reducing the disease burden among Chinese male patients with TC.

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in patients undergoing surgery for gastric cancer (GC). Although VTE incidence may vary among cancers, guidelines rarely stratify preventive methods for postoperative VTE by cancer type. The risk of VTE in patients undergoing surgery for GC remains unclear. METHODS: A systematic review and meta-analysis was undertaken to determine the risk of VTE after GC surgery and discuss the clinical value of pharmacological thromboprophylaxis in these cases. Medline, Embase, Web of Science, and Cochrane Library databases were searched for articles published from their inception to September 2022. RESULTS: Overall, 13 studies (111,936 patients) were included. The overall 1-month incidence of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) after GC surgery was 1.8% (95% CI, 0.8-3.1%; I²=98.5%), 1.2% (95% CI, 0.5-2.1%; I²=96.1%), and 0.4% (95% CI, 0.1-1.1%; I²=96.3%), respectively. The prevalence of postoperative VTE was comparable between Asian and Western populations (1.8% vs. 1.8%; P > 0.05). Compared with mechanical prophylaxis alone, mechanical plus pharmacological prophylaxis was associated with a significantly lower 1-month rate of postoperative VTE and DVT (0.6% vs. 2.9% and 0.6% vs. 2.8%, respectively; all P < 0.05), but not PE (P > 0.05). The 1-month postoperative incidence of VTE was not significantly different between laparoscopic and open surgery (1.8% vs. 4.3%, P > 0.05). CONCLUSION: Patients undergoing GC surgery do not have a high risk of VTE. The incidence of VTE after GC surgery is not significantly different between Eastern and Western patients. Mechanical plus pharmacological prophylaxis is more effective than mechanical prophylaxis alone in postoperative VTE prevention. The VTE risk is comparable between open and laparoscopic surgery for GC.

Joint Performance of a Continuous Glass Fiber/Polypropylene Composite.

Thermoplastic composite structures possess superior properties compared with thermosetting composites, including recyclability and high damage tolerance. However, the poor adhesion properties of thermoplastic composites make their joining process challenging. In this research, three bonding techniques, namely adhesive, mechanical joining, and hybrid bonding, are investigated using lap shear specimens to evaluate their mechanical properties and failure modes. The stress distributions at the joints of the three bonding techniques are analyzed by numerical simulation. The findings demonstrate that hybrid bonding enhances the strength of composite joints, albeit at the expense of some stiffness due to the presence of an open hole. This method is particularly suitable for applications that necessitate robust connections requiring high strength.

Simulation analysis of the three-party evolutionary game of green building market players under carbon trading policy.

Previous studies mainly focus on the game analysis of green building development under carbon tax policy, while carbon trading, as one of the important means to promote low-carbon development, is rarely mentioned in promoting the development of the green building market. Based on this, to study the impact of carbon trading policy on the development of the green building market, this study combines prospect theory for carbon trading to build a three-way evolutionary game model of developer-government-consumer. It studies the influencing causes of green building market development under the carbon trading mechanism from the whole perspective. The study shows the existence of a carbon trading policy helps the development of the green building market. In the presence of a carbon trading market, the government's punishment, subsidies, and the setting of carbon prices influence the development of the green building market. In addition, the percentage of carbon emissions bought, the potential benefits, and the selling price also affect the chance of consumers buying green buildings to a greater or lesser extent. This study introduces prospect theory into the developer-government-consumer three-way evolutionary game model, which enriches the research perspective of each subject's behavior in the green building market. It provides theoretical support for developers, governments, and consumers to collaborate to promote the coordination and development of the green building market. It has policy implications for promoting the green and high-quality development of the construction industry.

Prediction of lung papillary adenocarcinoma-specific survival using ensemble machine learning models.

Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific survival in LPADC using ensemble machine learning and classical Cox regression models. Moreover, models were evaluated to provide recommendations based on quantitative data for personalized treatment of LPADC. Data of patients diagnosed with LPADC (2004-2018) were extracted from the Surveillance, Epidemiology, and End Results database. The set of samples was randomly divided into the training and validation sets at a ratio of 7:3. Three ensemble models were selected, namely gradient boosting survival (GBS), random survival forest (RSF), and extra survival trees (EST). In addition, Cox proportional hazards (CoxPH) regression was used to construct the prognostic models. The Harrell's concordance index (C-index), integrated Brier score (IBS), and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the performance of the predictive models. A user-friendly web access panel was provided to easily evaluate the model for the prediction of survival and treatment recommendations. A total of 3615 patients were randomly divided into the training and validation cohorts (n = 2530 and 1085, respectively). The extra survival trees, RSF, GBS, and CoxPH models showed good discriminative ability and calibration in both the training and validation cohorts (mean of time-dependent AUC: > 0.84 and > 0.82; C-index: > 0.79 and > 0.77; IBS: < 0.16 and < 0.17, respectively). The RSF and GBS models were more consistent than the CoxPH model in predicting long-term survival. We implemented the developed models as web applications for deployment into clinical practice (accessible through https://shinyshine-820-lpaprediction-model-z3ubbu.streamlit.app/ ). All four prognostic models showed good discriminative ability and calibration. The RSF and GBS models exhibited the highest effectiveness among all models in predicting the long-term cancer-specific survival of patients with LPADC. This approach may facilitate the development of personalized treatment plans and prediction of prognosis for LPADC.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma.

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

CD44-Targeted Photoactivatable Polymeric Nanosystem with On-Demand Drug Release as a "Photoactivatable Bomb" for Combined Photodynamic Therapy-Chemotherapy of Cancer.

Nowadays, the combined use of chemotherapy and photodynamic therapy (PDT) remains the most popular strategy for cancer treatment with high theraprutic efficacy. However, targeted therapy with the on-demand release of drugs is what most clinical treatments lack, leading to heavy side effects. Herein, a new CD44-targeted and red-light-activatable nanosystem, Ru-HA@DOX nanoparticles (NPs), was developed by conjugating hydrophilic biodegradable hyaluronic acid (HA) and hydrophobic photoresponsive ruthenium (Ru) complexes, which could encapsulate the chemotherapeutic drug doxrubicin (DOX). Ru-HA@DOX NPs can selectively accumulate at the tumor through the enhanced permeability and retention (EPR) effect and CD44-mediated endocytosis, thus avoiding off-target toxicity during circulation. After 660 nm of irradiation at the tumor site, Ru-HA@DOX NPs, as a "photoactivatable bomb", was split via the photocleavable Ru-N coordination bond to fast release DOX and produce singlet oxygen (1O2) for PDT. In general, Ru-HA@DOX NPs retained its integrity before irradiation and possessed minimal cytotoxicity, while under red-light irradiation, Ru-HA@DOX NPs showed significant cytotoxicity due to the release of DOX and production of 1O2 at the tumor. Chemotherapy-PDT of Ru-HA@DOX NPs resulted in a significant inhibition of tumor growth in A549-tumor-bearing mice and reduced the cardiotoxicity of DOX. Therefore, this study offers a novel CD44-targeted drug-delivery system with on-demand drug release for synergistic chemotherapy-PDT.

Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine.

Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-ß-rutinoside/6-hydroxykaempferol 3,6-di-O-ß-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aß, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.

Overall survival prediction models for gynecological endometrioid adenocarcinoma with squamous differentiation (GE-ASqD) using machine-learning algorithms.

The actual 5-year survival rates for Gynecological Endometrioid Adenocarcinoma with Squamous Differentiation (GE-ASqD) are rarely reported. The purpose of this study was to evaluate how histological subtypes affected long-term survivors of GE-ASqD (> 5 years). We conducted a retrospective analysis of patients diagnosed GE-ASqD from the Surveillance, Epidemiology, and End Results database (2004-2015). In order to conduct the studies, we employed the chi-square test, univariate cox regression, and multivariate cox proportional hazards model. A total of 1131 patients with GE-ASqD were included in the survival study from 2004 to 2015 after applying the inclusion and exclusion criteria and the sample randomly split into a training set and a test set at a ratio of 7:3. Five machine learning algorithms were trained based on nine clinical variables to predict the 5-year overall survival. The AUC of the training group for the LR, Decision Tree, forest, Gbdt, and gbm algorithms were 0.809, 0.336, 0.841, 0.823, and 0.856 respectively. The AUC of the testing group was 0.779, 0.738, 0.753, 0.767 and 0.734, respectively. The calibration curves confirmed good performance of the five machine learning algorithms. Finally, five algorithms were combined to create a machine learning model that forecasts the 5-year overall survival rate of patients with GE-ASqD.

IGTCM: An integrative genome database of traditional Chinese medicine plants.

Fully understanding traditional Chinese medicines (TCMs) is still challenging because of the extreme complexity of their chemical components and mechanisms of action. The TCM Plant Genome Project aimed to obtain genetic information, determine gene functions, discover regulatory networks of herbal species, and elucidate the molecular mechanisms involved in the disease prevention and treatment, thereby accelerating the modernization of TCMs. A comprehensive database that contains TCM-related information will provide a vital resource. Here, we present an integrative genome database of TCM plants (IGTCM) that contains 14,711,220 records of 83 annotated TCM-related herb genomes, including 3,610,350 genes, 3,534,314 proteins and corresponding coding sequences, and 4,032,242 RNAs, as well as 1033 non-redundant component records for 68 herbs, downloaded and integrated from the GenBank and RefSeq databases. For minimal interconnectivity, each gene, protein, and component was annotated using the eggNOG-mapper tool and Kyoto Encyclopedia of Genes and Genomes database to acquire pathway information and enzyme classifications. These features can be linked across several species and different components. The IGTCM database also provides visualization and sequence similarity search tools for data analyses. These annotated herb genome sequences in IGTCM database are a necessary resource for systematically exploring genes related to the biosynthesis of compounds that have significant medicinal activities and excellent agronomic traits that can be used to improve TCM-related varieties through molecular breeding. It also provides valuable data and tools for future research on drug discovery and the protection and rational use of TCM plant resources. The IGTCM database is freely available at http://yeyn.group:96/.