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Abstract Metabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis.

Abstract Ions and radicals serve as key intermediates in molecular transformation, with their chemical properties being essential for understanding and predicting reaction reactivity and selectivity. In this data descriptor, we report a quantum chemical dataset named QM9star, comprising cations, anions, and radicals. This dataset is derived from the molecular structures of the QM9 dataset, created by removing terminal hydrogens followed by optimization using B3LYP-D3(BJ)/6-311 + G(d,p) level of density functional theory. The QM9star dataset includes approximately 1.9 million cations, anions, and radicals, along with 120 kilo neutral molecules prior to hydrogen removal. Each entry encompasses both molecular and atomic information: representative global properties include orbital energies, vibrational frequencies, etc., while local properties cover aspects such as charges and spin densities at each atomic site. The QM9star dataset not only serves as a comprehensive source of quantum chemical information for intermediates but also offers insights into the principle of atomic property distribution. We anticipate that these data will aid in machine learning studies related to chemical intermediates and contribute to the molecular representation learning.

Abstract The asymmetric Büchner reaction and related arene cyclopropanations represent one type of the powerful methods for enantioselective dearomatization. However, examples of asymmetric Büchner reactions via a non-diazo approach are quite scarce, and the related arene cyclopropanation based on alkynes has not been reported. Herein, we disclose an asymmetric Büchner reaction and the related arene cyclopropanation by copper-catalyzed controllable cyclization of N-propargyl ynamides via vinyl cation intermediates, leading to chiral tricycle-fused cycloheptatrienes and benzonorcaradienes in high yields and enantioselectivities. Importantly, this protocol represents an asymmetric arene cyclopropanation reaction of alkynes and an asymmetric Büchner reaction based on vinyl cations.

Abstract Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin–eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Abstract Background Apocrine carcinoma associated with Paget’s disease is a rare malignancy that typically manifests in elderly individuals, predominantly affecting the geriatric population. It commonly arises in regions rich in apocrine glands and often exhibits an insidious onset, potentially requiring several years to be diagnosed. Case presentation An 80-year-old male was simultaneously diagnosed with scrotal apocrine carcinoma (showing Paget changes) and early-stage gastric cancer. Whole-genome exome sequencing confirmed these as independent malignancies with minimal genetic overlap, indicating that they were two primary tumors. The patient initially underwent successful surgery but experienced recurrence and metastasis. Treatment with capecitabine and paclitaxel showed promising responses, highlighting similarities between breast and apocrine carcinomas. Challenges were noted in the use of genetic testing and drug susceptibility assessments for treatment guidance. Notably, HER-2 expression in metastatic lesions, a trait of apocrine carcinoma, has remained unexplored due to negative HER-2 FISH results and a lack of available targeted therapies in China. Conclusion Elderly patients often exhibit a lesser degree of aggressiveness toward treatment following a diagnosis of malignant tumors. It is imperative to carefully consider how to strike a balance between effective treatment and maintaining a satisfactory quality of life for these patients. This case underscores the complexity of treating coexisting rare cancers in older adults and emphasizes the need for personalized treatments and continued innovation in cancer therapy. The insights gained offer significant value in understanding and managing such rare cancer cases.

Abstract Abdominal aortic aneurysm (AAA) often remains undetected until rupture due to limited access to diagnostic ultrasound. This trial evaluated a deep learning (DL) algorithm to guide AAA screening by novice nurses with no prior ultrasonography experience. Ten nurses performed 15 scans each on patients over 65, assisted by a DL object detection algorithm, and compared against physician-performed scans. Ultrasound scan quality, assessed by three blinded expert physicians, was the primary outcome. Among 184 patients, DL-guided novices achieved adequate scan quality in 87.5% of cases, comparable to the 91.3% by physicians (p = 0.310). The DL model predicted AAA with an AUC of 0.975, 100% sensitivity, and 97.8% specificity, with a mean absolute error of 2.8 mm in predicting aortic width compared to physicians. This study demonstrates that DL-guided POCUS has the potential to democratize AAA screening, offering performance comparable to experienced physicians and improving early detection.

(1) Background: Over the past few decades, Jiangsu Province, China, has witnessed a remarkable surge in the incidence of prostate cancer (PCa), accompanied by notable demographic shifts; (2) Methods: PCa data for Jiangsu Province from 2009 to 2019 were obtained from the Jiangsu Cancer Registry. We calculated crude and age-specific incidence rates (ASIRs), average age at onset, and age-specific composition ratios. Standardization was performed based on the Segi’s world population. Birth cohorts (1929–2019) were analyzed to assess PCa incidence by birth year. Trend analysis was conducted using the Joinpoint Regression Model, and average annual percent changes (AAPCs) with corresponding 95% confidence interval (CI) were computed. A linear regression model was used to analyze the relationship between the average age at diagnosis and calendar years; (3) Results: The ASIRs of PCa in Jiangsu Province increased significantly, with an AAPC of 11.25% (95%CI: 10.09%, 12.42%) from 2009 to 2019. This increase was observed across all age groups, particularly among those aged 0–59 years. Birth cohort analysis revealed a rising trend with earlier birth years showing higher incidence, notably in the 1959 cohort. In rural areas, the age-standardized average age at onset of PCa decreased from 75.45 years in 2009 to 73.39 years in 2019, and the peak age group shifted from 75–79 years in 2009 to 70–74 years in 2019; (4) Conclusions: The rising incidence of PCa in Jiangsu Province, along with an increased proportion of cases in younger age groups, highlights the need for targeted interventions.

Abstract Background People with the metabolically obese normal weight (MONW) phenotype have been confirmed to significantly increase the risk of unfavorable health consequences. This study aimed to investigate the relationships between traditional and novel anthropometric indices with the MONW phenotype and compare the predictive ability of different anthropometric indices in identifying individuals with the MONW phenotype. Methods This cross-sectional study involved a total of 26,332 participants aged 18 years or older with a normal weight from Nanjing, China. Sociodemographic information, biochemical measurements, and anthropometric indices were collected. The novel body fat anthropometric indices included body shape index (ABSI), body roundness index (BRI), abdominal volume index (AVI), weight-adjusted-waist index (WWI), body adiposity index (BAI), conicity index (CI), waist-hip-height ratio (WHHR), as well as traditional indices such as waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR).The prevalence ratio (PR) from modified poisson regression and area under the receiver-operating characteristic curve (AUC) were conducted to compare the association and predictive capacity of different obesity indicators for the MONW phenotype. All analyses were stratified by sex. Results Modified poisson regression analyses revealed that weight, WC, HC, BMI, WHR, WHtR, ABSI, BRI, AVI, WWI, BAI, CI, and WHHR were independently associated with higher risk of the MONW phenotype, regardless of whether they were treated as a continuous or categorical variable (P

Circulating tumour cells (CTCs) and CTC clusters are considered metastatic precursors due to their ability to seed distant metastasis. However, navigating the bloodstream presents a significant challenge for CTCs, as they must endure fluid shear forces and resist detachment-induced anoikis. Consequently, while a large number of cells from the primary tumour may enter the circulation, only a tiny fraction will result in metastasis. Nevertheless, the metastatic potency dramatically increases when CTCs travel in conjunction with other cell types to form CTC clusters, including neutrophils, myeloid-derived suppressor cells, macrophages, platelets, cancer-associated fibroblasts and red blood cells found in circulation. Such heterotypic CTC clustering events have been identified in a variety of cancer types and may serve as intriguing therapeutic targets and novel biomarkers for liquid biopsy. This review summarises recent advances in microfluidic technologies designed for the isolation of CTC clusters and explores the biological properties of distinct types of CTC clusters within the circulatory system. Investigation of the mechanisms of CTC cluster–blood microenvironment interactions may offer a promising avenue for gaining fresh insights into CTC cluster-mediated metastatic progression and reveal potential opportunities for devising personalised antimetastasis treatments.

Abstract Background Insulin resistance (IR) and obesity are established risk factors for hypertension, with triglyceride-glucose (TyG) serving as a recognized surrogate marker for IR. The aim of this study was to investigate the association between TyG-BMI and hypertension in the general population. Methods A total of 60,283 adults aged ≥18 years who underwent face-to-face questionnaires, anthropometric measurements, and laboratory examination were included in this study. Multivariable logistic regression models and receiver operating characteristic curve (ROC) were used to determine the association between TyG-BMI and hypertension. The restricted cubic spline model was used for the dose-response analysis. Results After fully adjusting for confounding variables, multivariate logistic regression model showed a stable positive association between TyG-BMI and hypertension (OR: 1.61 per SD increase; 95% CI: 1.55–1.67; P-trend

Abstract Einstein–Podolsky–Rosen (EPR) steering is commonly shared among multiple observers by utilizing unsharp measurements. Nevertheless, their usage is restricted to local measurements and does not encompass all nonlocal measurement-based cases. In this work, a method for finding beneficial local measurement settings has been expanded to include nonlocal measurement cases. This method is applicable for any bipartite state and offers benefits even in scenarios with a high number of measurement settings. Using the Greenberger–Horne–Zeilinger state as an illustration, we show that employing unsharp nonlocal measurements can activate the phenomenon of steering sharing in contrast to using local measurements. Furthermore, our findings demonstrate that nonlocal measurements with unequal strength possess a greater activation capability compared to those with equal strength. Our activation method generates fresh concepts for conservation and recycling quantum resources.

Abstract Background Mechanical spinal cord injury (SCI) is a deteriorative neurological disorder, causing secondary neuroinflammation and neuropathy. ADAM8 is thought to be an extracellular metalloproteinase, which regulates proteolysis and cell adherence, but whether its intracellular region is involved in regulating neuroinflammation in microglia after SCI is unclear. Methods Using animal tissue RNA-Seq and clinical blood sample examinations, we found that a specific up-regulation of ADAM8 in microglia was associated with inflammation after SCI. In vitro, microglia stimulated by HMGB1, the tail region of ADAM8, promoted microglial inflammation, migration and proliferation by directly interacting with ERKs and Fra-1 to promote activation, then further activated Map3k4/JNKs/p38. Using SCI mice, we used BK-1361, a specific inhibitor of ADAM8, to treat these mice. Results The results showed that administration of BK-1361 attenuated the level of neuroinflammation and reduced microglial activation and recruitment by inhibiting the ADAM8/Fra-1 axis. Furthermore, treatment with BK-1361 alleviated glial scar formation, and also preserved myelin and axonal structures. The locomotor recovery of SCI mice treated with BK-1361 was therefore better than those without treatment. Conclusions Taken together, the results showed that ADAM8 was a critical molecule, which positively regulated neuroinflammatory development and secondary pathogenesis by promoting microglial activation and migration. Mechanically, ADAM8 formed a complex with ERK and Fra-1 to further activate the Map3k4/JNK/p38 axis in microglia. Inhibition of ADAM8 by treatment with BK-1361 decreased the levels of neuroinflammation, glial formation, and neurohistological loss, leading to favorable improvement in locomotor functional recovery in SCI mice. Graphical Abstract

Abstract Background Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. Methods A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. Results The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. Conclusion The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Abstract Background Cardiovascular disease (CVD) is a major global health threat, particularly in China, contributing to over 40% of deaths. While sleep behaviors, sedentary behaviors, and physical activities are recognized as independent lifestyle risk factors for CVD, there remains limited understanding of specific movement behavior patterns and their CVD risks, especially considering sex-specific differences. This study examines movement behavior patterns among Chinese adults (40–75) and their associations with cardiovascular risk, with a focus on sleep, physical activity (PA), and sedentary behavior (SB). Methods Data pertaining to 13,465 male participants and 15,613 female participants, collected from the Chronic Disease and Risk Factor Surveillance Survey in Nanjing from February 2020 to December 2022. The latent class analysis method was employed to identify underlying movement patterns across sexes. Multinomial logistic regression models assessed CVD risk, and the China-PAR model calculated 10-year risk. Results Three male and four female movement patterns emerged. Active Movers (17.10% males, 5.93% females) adhered to PA recommendations but had poorer sleep quality. Moderate Achievers (61.42% males, 45.32% females) demonstrated moderate behavior. Sedentary Sleepers (21.48% males, 10.20% females) exhibited minimal PA but good sleep. Female Moderate Physical Activity (MPA) Dominant Movers demonstrated a prevalent adherence to recommended MPA levels. Active movers had the lowest CVD risk. After adjusting for potential confounders, moderate achievers (OR = 1.462, 95% CI 1.212, 1.764) and sedentary sleepers (OR = 1.504, 95% CI 1.211, 1.868) were both identified as being associated with a high-risk of cardiovascular diseases (CVDs) compared to active movers in males, demonstrating a similar trend for intermediate risk. Such associations were not statistically significant among females. Conclusions Our study revealed sex-specific movement patterns associated with CVD risks among middle-aged Chinese adults. We suggest that adopting an active movement behavior pattern, characterized by meeting or exceeding recommended levels of vigorous physical activity (VPA) and reducing sedentary behavior, is beneficial for all middle-aged adults, particularly males. An active lifestyle could help counteract the adverse effects of relatively poor sleep quality on the risk of developing CVD in this population. Integrating sleep, PA, and SB information provides a holistic framework for understanding and mitigating CVD risks.

Abstract Background Osteoarthritis (OA) is a common degenerative joint condition marked by inflammation and cartilage breakdown. Currently, there is a dearth of treatment medications that can clearly slow the course of OA. Glaucocalyxin A (GLA) is a diterpene chemical identified and extracted from Rabdosia japonica with antithrombotic, anticoagulant, anti-tumor, anti-inflammatory, anti-oxidant, and other pharmacological properties. Previous research has linked inflammation to abnormalities in the homeostasis of the extracellular matrix (ECM). Although GLA has been shown to have anti-inflammatory qualities, its effects on the progression of OA are unknown. As a result, the goal of this study was to see if GLA could slow the course of OA. Methods ATDC5 cells were stimulated by IL-1β to create an inflammatory chondrocyte damage model. Quantitative polymerase chain reaction, Western Blot, high-density culture, and immunofluorescence were used to detect the expression levels of associated gene phenotypes. We also created a mouse model of OA induced by destabilization of the medial meniscus (DMM) instability, and GLA was administered intraperitoneally once every two days for eight weeks. Mice knee specimens were stained with hematoxylin–eosin, Safranin O/fast green, and immunohistochemical, and the Osteoarthritis Research Society International grade system and Mankin’s score were used to assess the protective effect of GLA on cartilage. Results In vitro and in vivo, we explored the effects and molecular processes of GLA as a therapy for OA. The findings demonstrated that GLA might reduce the expression of associated inflammatory mediators and protect the ECM by inhibiting the NF-κB and MAPK signaling pathways. Animal research revealed that GLA could protect against the DMM-induced OA model mice by stabilizing ECM. Conclusion Taken together, our findings show that GLA has a protective impact on cartilage throughout OA progression, implying that GLA could be employed as a possible therapeutic agent for OA, thus giving a new therapeutic method for the treatment of OA.

CH4 production rate of coalbed methane (CBM) well decreases rapidly during primary recovery in the deeply buried coal seam, resulting in a lot of CH4 residues. CO2 pour into deep coal seam with high stress sensitivity is available for enhancing CH4 recovery by improving permeability for reservoir fracture and displacing CH4 adsorbed in matrix. A coupled adsorp-hydro-thermo-mechanical (AHTM) model for deep methane development is established by considering the coupling relationships of non-isothermal and non-constant pressure competitive adsorption between CO2 and CH4, multi-phase flow, unsteady diffusion, heat transmission and in-situ stress variety. The model is verified by historical production and then used for CO2 enhanced CBM (CO2-ECBM) of deep coal reservoir in a sedimentary basin in Northwest China. The simulation results show that: (1) For primary recovery, permeability in coal reservoir drops rapidly with the development of CBM, which seriously restricts the production of CH4. The permeability of the reservoir decreases from 7.89 × 10−16 m2 to less than 1.50 × 10−16 m2, CH4 production rate in CBM well reduces to below 2000 m3/d, and the average total CH4 content of coal reservoir is reduced by 5.49 m3/t with the decrease of only 1.12 m3/t of average adsorbed CH4 in a production duration of 2000 d (2) With 10 MPa CO2 continuous injection into coal seam after 700d of primary, the permeability for reservoir and CH4 production rate increase while the total CH4 content and adsorption CH4 content in reservoir decrease compared with the primary recovery. (3) CO2 pouring into coal reservoir increases the CH4 production time and rate, which improves CH4 recovery of coal reservoir. And it increases by 23.36 %, 23.07 % and 22.46 % with shut-in thresholds of CH4 production rate of 1000 m3/d, 800 m3/d and 600 m3/d, respectively. The investigation is of great significance for the development of deep coalbed methane.

ObjectiveThis study aimed to characterize multivariate trajectories of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] jointly and examine their impact on incident cardiovascular disease (CVD) among a Chinese elderly medical examination population.MethodsA total of 13,504 individuals without CVD during 2018–2020 were included from the Chinese geriatric physical examination cohort study. The group-based trajectory model was used to construct multi-trajectories of systolic blood pressure and diastolic blood pressure. The primary outcome was the incidence of the first CVD events, consisting of stroke and coronary heart diseases, in 2021. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between BP multi-trajectories and incident CVD events.ResultsWe identified four blood pressure (BP) subclasses, summarized by their SBP and DBP levels from low to high as class 1 (7.16%), class 2 (55.17%), class 3 (32.26%), and class 4 (5.41%). In 2021, we documented 890 incident CVD events. Compared with participants in class 1, adjusted HRs were 1.56 (95% CI: 1.12–2.19) for class 2, 1.75 (95% CI: 1.24–2.47) for class 3, and 1.88 (95% CI: 1.24–2.85) for class 4 after adjustment for demographics, health behaviors, and metabolic index. Individuals aged 65 years and above with higher levels of BP trajectories had higher risks of CVD events in China.ConclusionsIndividuals with higher levels of both SBP and DBP trajectories over time were associated with an increased risk of incident CVD in the Chinese elderly population.

IntroductionPseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria.Methods and ResultsIn this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms.ConclusionWe identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.

BackgroundWith the increase in the aging population worldwide, Alzheimer’s disease has become a rapidly increasing public health concern. In the Global Burden of Disease Study 2019, there are three risk factors judged to have evidence for a causal link to Alzheimer’s disease and other dementias: smoking, high body-mass index (HBMI), and high fasting plasma glucose (HFPG).ObjectiveThis study aimed to analyze trends in AD mortality and the relevant burden across China from 1990 to 2019, as well as their correlation with age, period, and birth cohort.MethodsThe data were extracted from the GBD 2019. Trends in AD mortality attributable to metabolic risks (HFPG and HBMI) and smoking were analyzed using Joinpoint regression. The age-period-cohort (APC) model was used to evaluate cohort and period effects.ResultsFrom 1990 to 2019, the overall age-standardized mortality rate of AD increased, especially in women. There was an increase in AD mortality due to smoking in the net drift, and it was more significant in women (0.46, 95%CI = [0.09, 0.82]) than men (−0.03, 95%CI = [−0.11, 0.05]). For the cause of HFPG, the net drift values for men and women were 0.82% and 0.43%. For HBMI, the values were 3.14% and 2.76%, respectively, reflecting substantial increases in AD mortality.ConclusionTime trends in AD mortality caused by metabolic risks and smoking in China from 1990 to 2019 have consistently increased. Therefore, it is necessary to prevent excessive weight gain and obesity during the later stages of life, especially for females.

Abstract Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1‐positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low‐grade noninvasive and high‐grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial‐to‐mesenchymal transition generated TPCS. TPCS has stem‐cell‐like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell‐like epigenomic landscape, which might generate ITH without additional genetic diversification.

To fight against invasion by pathogens, plants have evolved an elaborate innate immune system, of which the nucleotide-binding domain leucine-rich repeat-containing receptor (NLR) acts as the sensor and immune executor. Potyviruses, comprising one of the largest genera of plant viruses, cause severe crop yield losses worldwide. Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development. This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae, Solanaceae, Brassicaceae, and Cucurbitaceae. It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.

Background/Aim. High-grade glioma (HGG) is an interstitial cell-derived primary tumor of the nervous system. The current guidelines for the diagnosis and treatment of glioma recommend the maximum safe range of tumor resection for treatment methods. Adjuvant concurrent chemoradiotherapy is recommended after surgery, followed by six cycles of single-drug chemotherapy, temozolomide. Evaluation of the early efficacy of concurrent chemoradio-therapy after HGG surgery, especially for patients with a high risk of recurrence, is a crucial step in enhancing the treatment efficiency for patients diagnosed with HGG. In this study, we investigated the clinical utility of magnetic resonance (MR) spectroscopy (MRS) in assessing the early curing impact of concurrent chemoradiotherapy following HGG surgery. Methods. A total of 50 patients with incomplete resection or suspected residual postoperative HGG, treated in the radiotherapy department of our hospital between January 2016 and June 2021, were selected for routine concurrent chemoradiotherapy. Conventional MR imaging and MRS were performed one week prior to treatment and one month after treatment to assess changes in specific brain metabolites. All 50 patients were followed up for 6 to 12 months. Based on the follow-up results, the patients were divided into two groups: the tumor recurrence group and the tumor suppression group. One month after the end of the treatment, the differences in levels of brain metabolites between the two groups were analyzed using MRS. Results. The levels of N-acetylaspartate (NAA) and creatine (Cr) increased after radiotherapy, while choline (Cho) peak value, and Cho/Cr, NAA/Cr, and Cho/NAA ratios decreased compared to pre-treatment levels. There were statistically significant differences in the NAA peak value, and Cho/Cr, and Cho/NAA ratios in the tumor enhancement area before and after treatment (p < 0.05). There were also statistically significant differences in Cho/Cr ratio in the peritumoral edema area before and after treatment (p < 0.05). Conclusion. After concurrent chemoradiotherapy, MRS can be used to detect early metabolic changes in the tumor enhancement and peritumoral edema areas of HGG.