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Xue-Lian Zhang,1 Ming-Xia Yuan,1 Gang Wan,2 Guang-Ran Yang,1 Dong-Mei Li,3 Han-Jing Fu,1 Liang-Xiang Zhu,1 Rong-Rong Xie,1 Jian-Dong Zhang,4 Yu-Jie Lv,5 Yu-Ling Li,6 Xue-Ping Du,7 Zi-Ming Wang,8 Xue-Li Cui,9 De-Yuan Liu,10 Ying Gao,11 Shu-Yan Cheng,12 Qian Wang,13 Yu Ji,14 Guang-Wei Li,15,16 Shen-Yuan Yuan1 1Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Medical Records and Statistics Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Clinical and Translational Science Institute, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; 4Department of General Practice, Jinsong Community Health Service Center, Beijing, People’s Republic of China; 5Department of General Practice, Cuigezhuang Community Health Service Center, Beijing, People’s Republic of China; 6Department of General Practice, Xinjiekou Community Health Service Center, Beijing, People’s Republic of China; 7Department of General Practice, Yuetan Community Health Service Center of Fuxing Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of General Practice, Jiangtai Community Health Service Center, Beijing, People’s Republic of China; 9Department of General Practice, Sanlitun Community Health Service Center, Beijing, People’s Republic of China; 10Department of General Practice, Zuojiazhuang Community Health Service Center, Beijing, People’s Republic of China; 11Department of General Practice, The First People’s Hospital of Chongwen District, Beijing, People’s Republic of China; 12Department of General Practice, Balizhuang Community Health Service Center, Beijing, People’s Republic of China; 13Department of General Practice, Majiapu Community Health Service Center, Beijing, People’s Republic of China; 14Department of Endocrinology, Beijing Aerospace General Hospital, Beijing, People’s Republic of China; 15Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 16Center of Endocrinology and Cardiovascular Disease, Department of Endocrinology, National Center of Cardiology and Fuwai Hospital, Beijing, People’s Republic of China Objective: It is well known that diabetic kidney disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). In this study, the effects of urine albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population of T2DM. Methods: The study was carried out using recorded information of a cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were enrolled in an 8 years prospective study and received multifactorial intervention. The risk of CVD outcomes was assessed according to chronic kidney disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2). The effects of AER and eGFR on risk of CVD onset were also analyzed. Results: During the follow-up period (median 6.8 years), 71 CVD events occurred. At baseline, those with AER ≥300 mg/d and coexisting eGFR 60–89 mL/min/ 1.73 m2 or

Haijuan Hu, Jidong Zhang, Yan Wang, Zejun Tian, Demin Liu, Guangming Zhang, Guoqiang Gu, Hongmei Zheng, Ruiqin Xie, Wei Cui Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China Background: The objective of the study was to investigate the relationship between baseline blood pressure (BP) and the magnitude of BP reduction in patients with essential hypertension treated with nifedipine gastrointestinal therapeutic system (NGTS).Methods and patients: One hundred and thirty-eight patients with essential hypertension were enrolled in this prospective, single-arm, open-label study. NGTS was administered for 24 weeks to achieve target BP of 140/90 mmHg. The dose could be uptitrated to 60 mg/d in case of unsatisfactory BP reduction after 4-week treatment. Home blood pressure measurement was recorded through the initial 1–14 days, and office BP and heart rate were evaluated at 2, 4, 8, 12, and 24 weeks.Results: One hundred and seventeen patients (84.8%) completed the study, and their average BP decreased by 19.0/11.3 mmHg after 24 weeks. The reduction of either systolic or diastolic BP was positively correlated with baseline BP at weeks 2, 4, or 24 after treatment (r=0.603–0.762, all p

Objective: To evaluate the value of ultrasonography in non-displaced and mini-displaced humeral lateral condyle fractures in children.Methods: Nine children aged 2-9 years with non-displaced or mini-displaced humeral lateral condyle fractures were examined by high-resolution ultrasonography. The fracture line through the joint surface was visualized by ultrasonography in 6 case, in which closed reduction and percutaneous pinning was performed on 3 patients and other 3 patients did not receive the treatment because of patients'or their parents'refusal. In the remaining 3 children, ultrasonography did not reveal the cartilaginous trochle involvement at the joint surface and conservative treatment was adopted.Results: The average follow-up period was 8 months. The sonographic findings were confirmed by magnetic resonance imaging in one child who received conservative treatment and another child who received percutaneous pinning. The elbow function and fracture healing were good in cases received closed reduction and percutaneous pinning. Among the three cases who refused to receive closed reduction and internal fixation, re-displacement occurred in 1 case and delayed union in 1 case. All three cases receiving conservative treatment had good results both in elbow function and fracture healing.Conclusion: High-resolution ultrasonography enable to reveal non-displaced and mini-displaced humeral lateral condyle fractures as well as to ascertain whether the cartilaginous trochlea humeri was involved. For these cases, arthrography or magnetic resonance imaging is unnecessary. [ABSTRACT FROM AUTHOR]

Colchicine is a widely prescribed anti-inflammatory drug for the treatment of gout, familial Mediterranean fever and pericarditis, but its narrow therapeutic window presents a significant risk of severe toxicity. Despite its clinical relevance, the molecular mechanisms underlying colchicine's pharmacological effects and associated toxicity and explored potential therapeutic interventions to mitigate its adverse effects. We showed the colchicine's impact on cellular morphology in human umbilical vein endothelial cells (HUVEC) and HeLa cells including cell rounding and detachment following 24 h of exposure that revealed pronounced cytotoxic effects. We then established a large-scale screening model to identify small molecules capable of reversing colchicine-induced cellular toxicity, and identified MLN4924, an inhibitor of the Cullin-RING E3 ligase (CRL) system, as a promising candidate for mitigating colchicine-induced cellular injury. Through a comprehensive multi-omics approach including transcriptomics, proteomics, phosphoproteomics and ubiquitinomics, we systematically characterized the molecular perturbations caused by colchicine and delineated the protective mechanisms of MLN4924. We found that MLN4924 exerted its protective effects by modulating critical cellular pathways, specifically preventing the dysregulation of cell cycle progression, mitotic disruption and microtubule destabilization triggered by colchicine. Furthermore, proteomic and phosphoproteomic analyses revealed significant alterations in kinase signaling networks, with combined inhibition of CDK1 and PAK1 emerging as an effective strategy to counteract colchicine-induced cellular dysfunction. These results not only provide a detailed molecular characterization of colchicine toxicity but also identify key therapeutic targets, laying the groundwork for the development of targeted interventions to mitigate colchicine-induced adverse effects in clinical practice., Competing Interests: Competing interests: The patent application (ZL 2021 1 0280667.1) was filed by Min-jia Tan, Bin Liu, and Lin-hui Zhai for the novel application of MLN4924 in alleviating colchicine poisoning. All the authors in this project declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The potential universality of chemical transformation principles makes it a powerful tool for nanocrystal (NC) synthesis. An example is the nanoscale Kirkendall effect, which serves as a guideline for the construction of hollow structures with different properties compared to their solid counterparts. However, even this general process is still limited in material scope, structural complexity, and, in particular, transformations beyond the conventional solid-to-hollow process. We demonstrate in this work an extension of the Kirkendall effect that drives reversible structural and phase transformations between metastable metal chalcogenides (MCs) and metal phosphides (MPs). Starting from Ni 3 S 4 /Cu 1.94 S NCs as the initial frameworks, ligand-regulated sequential extractions and diffusion of host/guest (S 2- /P 3- ) anions between Ni 3 S 4 /Cu 1.94 S and Ni 2 P/Cu 3 P phases enable solid-to-hollow-to-solid structural motif evolution while retaining the overall morphology of the NC. An in-depth mechanistic study reveals that the transformation between metastable MCs and MPs occurs through a combination of ligand-dependent kinetic control and anion mixing-induced thermodynamic control. This strategy provides a robust platform for creating a library of reconfigurable NCs with tunable compositions, structures, and interfaces.

Background: Environmental pollution seriously endangers people's physical and mental health, especially the health of middle-aged and elderly people. Environmental pollution, trade openness, and population health are interconnected. Environmental pollution may have a nonlinear impact on health, and the impact of trade openness on the health effects of environmental pollution may not be a simple strengthening or weakening effect. However, few studies have used threshold effects model to explore the nonlinear mechanisms of environmental pollution's impact on health in China. As a result, this study incorporates trade openness into the research framework on the health effects of environmental pollution, aiming to study the mechanism of environmental pollution on health., Methods: Using the China Health and Retirement Longitudinal Study (CHARLS) data from 2013 to 2020 and the data of 111 prefecture-level cities in China, we combine two-way fixed-effects models and threshold models to explore the effects of environmental pollution on the health of middle-aged and elderly people and the role of trade openness in the path of environmental pollution affecting health., Results: Environmental pollution impairs the health of middle-aged and elderly people, and there is a single threshold effect and regional heterogeneity in this negative impact. Trade openness has the effect of first weakening and then strengthening in the inhibitory effect of environmental pollution on health., Conclusion: The negative impact of environmental pollution on health has regional heterogeneity, and there is a nonlinear relationship between environmental pollution and the health of middle-aged and elderly people. The health effect of environmental pollution is mainly long-term effect, and trade openness has a threshold effect on the impact of environmental pollution on health. Therefore, instead of adopting a one-size-fits-all policy, environmental and economic policies should be customized according to the degree of environmental pollution, trade openness, and regional variations, so as to safeguard the health of middle-aged and elderly individuals through effective environmental governance., (© 2024. The Author(s).)

Phagocytosis is an indispensable function of microglia, the brain professional phagocytes. Microglia is particularly efficient phagocytosing cells that undergo programmed cell death (apoptosis) in physiological conditions. However, mounting evidence suggests microglial phagocytosis dysfunction in multiple brain disorders. These observations prompted us to search for phagocytosis modulators (enhancers or inhibitors) with therapeutic potential. We used a bottom-up strategy that consisted on the identification of phagocytosis modulators using phenotypic high throughput screenings (HTSs) in cell culture and validation in organotypic cultures and in vivo. We performed two complementary HTS campagnes: at Achucarro, we used primary cultures of mouse microglia and compounds of the Prestwick Chemical Library; at Roche, we used human iPSC derived macrophage-like cells and a proprietary chemo-genomic library with 2200 compounds with known mechanism-of-action. Next, we validated the more robust compounds using hippocampal organotypic cultures and identified two phagocytosis inhibitors: trifluoperazine, a dopaminergic and adrenergic antagonist used as an antipsychotic and antineoplastic; and deoxytubercidin, a ribose derivative. Finally, we tested whether these compounds were able to modulate phagocytosis of apoptotic newborn cells in the adult hippocampal neurogenic niche in vivo by administering them into the mouse hippocampus using osmotic minipumps. We confirmed that both trifluoperazine and deoxytubercidin have anti-phagocytic activity in vivo, and validated our bottom-up strategy to identify novel phagocytosis modulators. These results show that chemical libraries with annotated mechanism of action are an starting point for the pharmacological modulation of microglia in drug discovery projects aiming at the therapeutic manipulation of phagocytosis in brain diseases., (© 2024 F. Hoffmann‐La Roche Ltd and The Author(s). GLIA published by Wiley Periodicals LLC.)

Because of the unique and superior optoelectronic properties, metal halide perovskites (MHPs) have attracted great interest in photocatalysis. Element doping strategy is adopted to modify perovskite materials to improve their photocatalytic performance. However, the contribution of bare doping-site onto photocatalytic efficiency, and the correlation between doping locations and activity have not yet to be demonstrated. The unique properties of non-active alkali metals promoted us to systematically explore the potential of A-site-doped MHPs for photocatalysis. Herein, we dope potassium (K + ) into CsPbBr 3 via an anti-solvent precipitation method and first reveal that the occupied locations of K + in CsPbBr 3 is lattice incorporation rather than surface segregation, which would change from A-site substitution to interstitial site in lattice with the increase of K + concentrations. Taking hydrogen (H 2 ) evolution as a model reaction, photocatalytic activity of CsPbBr 3 after K + doping could be significantly improved ~11-fold with A-site substitution, which is superior to that of interstitial site doping. Moreover, other alkali metals including lithium (Li), sodium (Na), and rubidium (Rb) doping give the same results. The structure of photocatalysts during reaction confirmed the contribution of A-site doping onto enhanced photocatalytic activity. Mechanistic insights show it is a result of the relaxed lattice strain induced promoted charge-carriers dynamics and upward shifting of band after K + A-site doping., (© 2024 Wiley-VCH GmbH.)

Captivity is a key strategy for protecting endangered species, but research has primarily focused on artificial breeding and reintroduction to bolster wild populations, often overlooking the environmental and health risks associated with antibiotic resistance genes (ARGs). Here, we conducted a comprehensive analysis of the microbiome and ARG profiles in the gut of wild giant pandas across five representative populations, as well as one captive population, utilizing 16S rRNA gene sequencing and High-Throughput Quantitative PCR. Our findings revealed that both geographic location and captivity significantly influenced the gut microbial community and ARG composition in the gut of giant pandas. Additionally, we identified core microbiomes with essential ecological functions, particularly those related to food utilization, were identified in the giant panda gut across different regions. The gut ARGs in giant pandas exhibited a broad range of subtypes, with multidrug resistance genes being the most prevalent. Notably, the captive population harbored the highest abundance of high-risk ARGs, especially those conferring tetracycline resistance. High-risk multidrug ARGs (e.g., tolC, mepA, and mdtA) were found to be strongly correlated with the potential pathogens, such as Escherichia_Shigellina and Pseudomonas. Furthermore, bamboo-associated ARGs and mobile genetic elements (MGEs) contributed significantly to the ARG abundance in the giant panda gut, indicating that diet plays a crucial role in shaping gut resistome. Collectively, our study provides a detailed mapping of giant panda gut microbiomes and ARG distribution, offering valuable insights for conservation efforts and advancing our understanding of ARG dynamics in giant panda populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Most fluorogens with aggregation-induced emission (AIE) characteristics are hydrophobic and most common sugars are hydrophilic and naturally nontoxic. The combination of AIEgens and sugars can construct glycosyl AIEgens with the advantages of good water-solubility, low fluorescent background and satisfactory biocompatibility. Based on the specific reaction or binding with analytes to change the conjugate system or restrict intramolecular motions, glycosyl AIEgens can be used as powerful tools for detecting bioactive molecules or imaging living cells. In this feature article, we summarize recent advances in sugar-based AIE luminogens and their applications in biosensing and imaging. The sugar units could significantly increase the solubility, biocompatibility, target activity, and chemical modifying capacity and often decrease the background fluorescence of the AIE probes. Corresponding studies not only expand the application fields of AIEgens but also provide effective tools for broad carbohydrate research.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care., (© 2024. The Author(s).)

Background: The lipid accumulation product (LAP) and the visceral adiposity index (VAI) are suggested as dependable measures for assessing visceral fat levels. Prediabetes is recognized as a condition that precedes the potential onset of diabetes. The objective of this research is to investigate how VAI and LAP are related to prediabetes among the adult population in the United States., Methods: Information from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) was scrutinized in a cross-sectional study. To evaluate the connection between VAI or LAP and the presence of prediabetes, both univariate analysis and multivariate logistic regression were utilized. Threshold effect analysis and fitted smoothing curves were used to delve into the non-linear association between VAI or LAP and prediabetes. Additional analyses were performed on specific subgroups, along with tests to explore potential interactions., Results: In general, 12,564 American adults were included. After full adjustment, prediabetes with VAI (OR: 1.128, 95% CI: 1.073-1.185) or LAP (OR: 1.006, 95% CI: 1.004-1.008) showed a positive correlation. Individuals in the 4th VAI quartile group faced a significant 61.9% elevated risk for prediabetes (OR: 1.619, 95% CI: 1.354-1.937) when contrasted to those in the 1st VAI quartile. Participants in the 4th LAP quartile group had a significant 116.4% elevated risk for prediabetes (OR: 2.164, 95% CI: 1.747-2.681) when contrasted to individuals of the 1st LAP quartile. Smooth curve fitting analysis revealed a nonlinear correlation of VAI or LAP and prediabetes, and threshold effect analysis was used to determine an inflection point of 4.090 for VAI and 68.168 for LAP., Conclusions: The values of VAI and LAP are positively associated with the prevalence of prediabetes. The VAI and LAP indices may be used as predictors of prediabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally., Methods: We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990-2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age‑period‑cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature., Results: In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14-4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019., Conclusion: There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations., (© 2024. The Author(s).)

Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, presents significant health challenges, and the intricate connection between insomnia and AF has garnered substantial attention. This cohort study aims to investigate the relationship between insomnia and AF recurrences following radiofrequency ablation., Materials and Methods: Data were retrieved from an electronic database of patients who underwent radiofrequency ablation for AF. The primary endpoint was AF recurrence. We utilized a multivariable Cox model, coupled with three propensity score methods, for analysis., Results: Between January 1, 2017, and June 1, 2022, 541 patients who underwent radiofrequency ablation for AF were recorded in the database. After excluding 185 patients, the final cohort comprised 356 patients. Among them, 68 were afflicted by insomnia, while 288 were not. Over a median follow-up of 755 days, one patient died, and 130 (36.5%) experienced AF recurrence. Multivariate Cox regression analysis revealed that the insomnia group had a higher risk of AF recurrence compared to the non-insomnia group (HR: 1.83, 95% CI: 1.16-2.89). Further landmark analysis showed no significant difference in AF recurrence rates during the initial 1-year follow-up. However, beyond 1 year, the insomnia group demonstrated a significantly higher AF recurrence rate. As the number of insomnia symptoms increased, the risk of AF recurrence also rose significantly, indicating a dose-response relationship., Conclusion: This study establishes a significant link between insomnia and long-term AF recurrence following radiofrequency ablation. It underscores the importance of identifying and addressing insomnia in patients with AF undergoing radiofrequency ablation.

Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs), enabling precise determination of their reactivity and properties. Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact for the factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co 3 S 4 -MoS 2 heteronanostructures (HNs) via cation exchange. MoS 2 in parent Cu 1.94 S-MoS 2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co 3 S 4 -MoS 2 HNs with controlled phase. This MoS 2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its diversity. Further, theoretical calculations demonstrate that Co 3 S 4 (111)/MoS 2 (001) exhibits a higher adhesion work, providing further evidence that MoS 2 enables phase control in the HNs CE reactions, inducing the generation of novel Co 3 S 4 -MoS 2 HNs. As a proof-of-concept application for crystal phase- and dimensionality-dependent of cobalt sulfide based HNs, the obtained Co 3 S 4 -MoS 2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique design strategy to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering that are otherwise inaccessible., (© 2024 Wiley-VCH GmbH.)

Motivation: Analysis of alternative splicing using short-read RNA-seq data is a complex process that involves several steps: alignment of reads to the reference genome, identification of alternatively spliced features, motif discovery, analysis of RNA-protein binding near donor and acceptor splice sites, and exploratory data visualization. To the best of our knowledge, there is currently no integrative open-source software dedicated to this task., Results: Here, we introduce splicekit , a Python package that provides and integrates a set of existing and novel splicing analysis tools for conducting splicing analysis., Availability and Implementation: The software splicekit is open-source and available at Github (https://github.com/bedapub/splicekit) and via the Python Package Index., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China., Methods: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software., Results: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines., Conclusion: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps., (© 2024. The Author(s).)

The synthesis of transition metal nitrides nanocrystals (TMNs NCs) has posed a significant challenge due to the limited reactivity of nitrogen sources at lower temperatures and the scarcity of available synthesis methods. In this study, we present a novel colloidal synthesis strategy for the fabrication of Cu 3 N nanorods (NRs). It is found that the trace oxygen (O 2 ) plays an important role in the synthesis process. And a new mechanism for the formation of Cu 3 N is proposed. Subsequently, by employing secondary lateral epitaxial growth, the Cu 3 N-Cu 2 O heteronanostructures (HNs) can be prepared. The Cu 3 N NRs and Cu 3 N-Cu 2 O HNs were evaluated as precursor electrocatalysts for the CO 2 reduction reaction (CO 2 RR). The Cu 3 N-Cu 2 O HNs demonstrate remarkable selectivity and stability with ethylene (C 2 H 4 ) Faradaic efficiency (FE) up to 55.3%, surpassing that of Cu 3 N NRs. This study provides innovative insights into the reaction mechanism of colloidal synthesis of TMNs NCs and presents alternative options for designing cost-effective electrocatalysts to achieve carbon neutrality.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC., (© 2024. The Author(s).)

Resolving the separation between two incoherent optical sources with high precision is of great significance for fluorescence imaging and astronomical observations. In this paper, we focus on a more general scenario where two sources have unequal brightnesses. We give the ultimate precision limit with respect to separation by using the quantum Fisher information. Through the calculation of the classical Fisher information, we analyze and compare several specific measurement schemes including direct measurement, Gaussian mode measurement and zero-photon measurement. The results indicate that Gaussian mode measurement is the nearly optimal for a small separation. On this basis, the effects of relative brightness fluctuation are addressed. Our work provides a positive complement to the aspect of superresolution imaging of incoherent sources.