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Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. Methods We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. Results ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85–0.96). Additionally, with F% = 4.05% as the threshold, the Youden’s J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P

Abstract High-quality standard views in two-dimensional echocardiography are essential for accurate cardiovascular disease diagnosis and treatment decisions. However, the quality of echocardiographic images is highly dependent on the practitioner’s experience. Ensuring timely quality control of echocardiographic images in the clinical setting remains a significant challenge. In this study, we aimed to propose new quality assessment criteria and develop a multi-task deep learning model for real-time multi-view classification and image quality assessment (six standard views and “others”). A total of 170,311 echocardiographic images collected between 2015 and 2022 were utilized to develop and evaluate the model. On the test set, the model achieved an overall classification accuracy of 97.8% (95%CI 97.7–98.0) and a mean absolute error of 6.54 (95%CI 6.43–6.66). A single-frame inference time of 2.8 ms was achieved, meeting real-time requirements. We also analyzed pre-stored images from three distinct groups of echocardiographers (junior, senior, and expert) to evaluate the clinical feasibility of the model. Our multi-task model can provide objective, reproducible, and clinically significant view quality assessment results for echocardiographic images, potentially optimizing the clinical image acquisition process and improving AI-assisted diagnosis accuracy.

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

Abstract Early patterning of DNA methylation (DNAm) may play an important role in later disease development. To better understand intergenerational epigenetic inheritance, we investigated the correlation between DNAm in blood in mother-newborn and in father-newborn pairs in the Isle of Wight (IoW) birth cohort. For parent-newborn pairs (n = 48), offspring DNAm was measured in cord blood and the parent’s DNAm in whole blood. Mothers’ DNAm was analyzed at birth (Guthrie card), age 18, early and late pregnancy respectively, and fathers’ DNAm was measured during the mother’s pregnancy. Linear regressions were applied to assess the intergenerational correlation of parental DNAm with that of offspring. Among various pairs of mother-newborn and father-newborn DNAm, the pairs where the mothers’ DNAm was measured at age 18 years exhibited the highest number of CpGs with significant intergenerational correlation in DNAm, with 1829 CpGs (0.54%) of the 338,526 CpGs studied (FDR

Abstract Objectives Newly detected hepatic nodules during follow-up of cancer survivors receiving chemotherapy may pose a diagnostic dilemma. We investigated a series of hepatic focal nodular hyperplasia (FNH) diagnosed by either typical MRI features and follow-up or pathology in cancer survivors. Methods This retrospective study evaluated 38 patients with tumours who developed new hepatic FNH after cyclophosphamide-based (n = 19) and oxaliplatin-based (n = 19) chemotherapies. The main tumour types were breast cancer (n = 18) and colorectal cancer (n = 17). MRI findings, clinical features, and temporal evolution of all target hepatic lesions (n = 63) were reported. In addition, the two chemotherapy drug groups were compared. Results The median interval between chemotherapy completion and FNH detection was 30.4 months (12.9, 49.4). Six patients underwent biopsy or surgery, while the remaining patients were diagnosed based on typical MRI features and long-term follow-up. Among the patients, 60.5% (23/38) presented with multiple nodules and 63 target lesions were detected. The median size of target lesions was 11.5 mm (8.4, 15.1). The median follow-up time was 32.5 months (21.2, 48.6), and 15 patients experienced changes in their lesions during the follow-up period (11 increased and 4 decreased). The cyclophosphamide-based treatment group had a younger population, a greater proportion of females, and a shorter time to discovery than the oxaliplatin-based chemotherapy group (all p ≤ 0.016). Conclusions FNH may occur in cancer survivors after cyclophosphamide- or oxaliplatin-based chemotherapy. Considering a patient’s treatment history and typical MRI findings can help avoid misdiagnosis and unnecessary invasive treatment. Clinical relevance statement When cancer survivors develop new hepatic nodules during follow-up, clinicians should think of the possibility of focal nodular hyperplasia in addition to liver metastasis, especially if the cancer survivors were previously treated with cyclophosphamide or oxaliplatin. Key Points Cancer survivors, after chemotherapy, can develop hepatic focal nodular hyperplasia. Cyclophosphamide and oxaliplatin are two chemotherapeutic agents that predispose to focal nodular hyperplasia development. Focal nodular hyperplasia occurs at shorter intervals in patients treated with cyclophosphamide. Graphical Abstract

Abstract Background Occupational stress can affect specialty nurses’ quality of work, especially for those working in care units. This study, therefore, investigated role stress and its related factors among specialty nurses working in tertiary general hospitals. Methods This cross-sectional descriptive study used convenience sampling to recruit 795 Chinese specialty nurses in 11 tertiary general hospitals (from February to March 2023). A questionnaire survey was conducted using the Basic Information Questionnaire and the Role Stress Scale. Multiple linear regression analyses were performed on the survey data to explore the factors affecting role stress. Results The total role stress score of specialty nurses in tertiary general hospitals was 52.05 ± 19.98. The highest mean item score was quantitative overload, followed by qualitative overload, role conflict, and role ambiguity, which had the lowest score. Multiple linear regression analysis revealed that gender (β = -0.085, p

The nabla fractional-order uncertain difference equation with Caputo-type was analyzed in this article. To begin, the existence and uniqueness theorem of solutions for nabla Caputo uncertain difference equations with almost surely bounded uncertain variables was presented. Furthermore, the uncertainty distributions of the solutions for the proposed equations were obtained by establishing a connection between the solutions of equations and their α-paths based on new comparison theorems. Finally, an application of the uncertain difference equations in a logistic population model involving Allee effect was provided and examples were performed to demonstrate the validity of the theoretical results presented.

Abstract Modeling user intention with limited evidence in short-term historical sequences is a major challenge in session recommendation. In this domain, research exploration extends from traditional methods to deep learning. However, most of them solely concentrate on the sequential dependence or pairwise relations within the session, disregarding the inherent consistency among items. Additionally, there is a lack of research on context adaptation in session intention learning. To this end, we propose a novel session-based model named C-HAN, which consists of two parallel modules: the context-embedded hypergraph attention network and self-attention. These modules are designed to capture the inherent consistency and sequential dependencies between items. In the hypergraph attention network module, the different types of interaction contexts are introduced to enhance the model’s contextual awareness. Finally, the soft-attention mechanism efficiently integrates the two types of information, collaboratively constructing the representation of the session. Experimental validation on three real-world datasets demonstrates the superior performance of C-HAN compared to state-of-the-art methods. The results show that C-HAN achieves an average improvement of 6.55%, 5.91%, and 6.17% over the runner-up baseline method on Precision@K, Recall@K, and MRR evaluation metrics, respectively.

Most recently, high-entropy alloys (HEAs) with 5 or more elements open a new area for materials exploration with substantial mechanical properties. The large composition space and numerous structures of HEAs bring significant difficulties for phase design and determination of mechanical property. Machine learning, one of most rapidly growing scientific and technical field, meets at the intersection of computer science and materials science, and at the center of artificial intelligence. Machine learning provides the opportunity to build up the relationship between multiple physical properties and mechanical properties. The fast changes of this field call for significant practice for materials community to utilize it as a more efficient, accurate and interpretable tool. In this review, we summarize the most promising machine learning models, combined with high-throughput simulation and experimental screening, to predict and fabricate HEAs with desired superb mechanical properties.

Abstract Background Myopia is increasing in prevalence worldwide. Combination therapy showed a better effect on myopia control than monotherapy. Repeated low-level red light therapy (RLRL) therapy and defocus-incorporated multiple segment (DIMS) spectacle lenses have been reported to retard myopia progression significantly. However, whether these two therapies are better than one is still unknown. The present study aims to report the study protocol of a trial designed to evaluate the efficacy and safety of combination therapy of RLRL and DIMS versus DIMS alone for reducing the progression of myopia among Chinese school-aged children. Methods This study is a 12-month, randomized, parallel-controlled, single-center clinical trial. We will recruit children aged 8–12 years with spherical equivalence (SE) between − 0.50 D and − 6.00 D under cycloplegia in both eyes. We will recruit 66 participants with an allocation ratio of 1:1 from our hospital. Participants in the intervention group will be treated with an RLRL therapy device twice a day from Monday to Friday at home, 3 min per session, with a minimum interval of 4 h, under the supervision of their parents/guardians. They will wear DIMS spectacles for myopia correction during the day. Participants in the control group will not receive the RLRL therapy and will only wear DIMS spectacles to correct myopia. Participants from both groups will attend the hospital every 6 months. The primary outcome is the change in axial length at 12 months. Secondary outcomes include changes in refraction under cycloplegia, optical coherence tomography (OCT), multifocal electroretinogram (mfERG), color vision, and participants’ self-reporting of adverse events at 12 months. Discussion This study will report the efficacy and safety outcome of the combination therapy of RLRL and DIMS versus DIMS for school-aged children with myopia in detail. Trial registration ChiCTR2300075398. Registered 4 September 2023. https://www.chictr.org.cn/bin/project/edit?pid=200751 .

Laser powder bed fusion (LPBF) Al–Li alloy technology demonstrates adaptability to the development requirements of structural complexity and functional integration, making it a promising area of research in additive manufacturing for the aerospace, defense industry, and other fields. However, challenges such as microstructure anisotropy and metallurgical defects inevitably arise during the LPBF process of lightweight alloys, significantly impeding further enhancements in their formability properties. Some improvement measures offer a viable solution to enhance the microstructure, mitigate metallurgical defects, and optimize residual stress distribution in additive structures, thereby enabling high–performance Al–Li alloy production by LPBF. This paper first introduces the fundamental principle of LPBF and discusses the process of parameter optimization for LPBF Al–Li alloys. It then describes the typical microstructures and common metallurgical defects of LPBF Al–Li alloys, along with examining the evolution process of microstructures and formation mechanism of metallurgical defects. Specifically, it focuses on discussing the influence of Li element on solidification structure. On this basis, it presents the mechanical properties and anisotropy of mechanical properties for LPBF Al–Li alloys. Afterward, a comprehensive review is provided of the current research status regarding LPBF improvement measures, including powder alloying, heat treatment, and other technologies. Emphasis is placed on improvements in microstructure anisotropy and reductions in metallurgical defects through these improvement measures. Finally, this article summarizes the research progress made in LPBF Al–Li alloys and its improvement measures while also prospecting future research work.

Abstract Background Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China’s NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. Methods Children hospitalised for LRTI at the Department of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. Results Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p

The goal of palliative care is to help patients and their families improve their quality of life,reflect the core content of professional ethics of medical care,and respect the life value and personality dignity of patients,including relieving physical,mental,and psychological pain and meeting the needs of patients to prolong their lives through analgesia and controlling various symptoms.This article expounds the integration of palliative care concept into geriatric medical education,provides a sustainable development teaching mode and practical experience for the training of geriatric medical workers,improves the quality of geriatric medical education,improves the post competence of geriatric specialists,and provides certain ideas for the establishment of comprehensive and standardized geriatric medical education.

Abstract Salicylic acid (SA) is a multi-functional phytohormone, regulating diverse processes of plant growth and development, especially triggering plant immune responses and initiating leaf senescence. However, the early SA signaling events remain elusive in most plant species apart from Arabidopsis, and even less is known about the multi-facet mechanism underlying SA-regulated processes. Here, we report the identification of a novel regulatory module in cucumber, CsNPR1-CsWRKY11, which mediates the regulation of SA-promoted leaf senescence and ROS burst. Our analyses demonstrate that under SA treatment, CsNPR1 recruits CsWRKY11 to bind to the promoter of CsWRKY11 to activate its expression, thus amplifying the primary SA signal. Then, CsWRKY11 cooperates with CsNPR1 to directly regulate the expression of both chlorophyll degradation and ROS biosynthesis related genes, thereby inducing leaf de-greening and ROS burst. Our study provides a solid line of evidence that CsNPR1 and CsWRKY11 constitute a key module in SA signaling pathway in cucumber, and gains an insight into the interconnected regulation of SA-triggered processes.

Abstract Background Cadmium (Cd) is extremely toxic and non-essential for plants. Different soybean varieties differ greatly in their Cd accumulation ability, but little is known about the underlying molecular mechanisms. Results Here, we performed transcriptomic analysis using Illumina pair-end sequencing on root tissues from two soybean varieties (su8, high-Cd-accumulating (HAS) and su7, low Cd-accumulating (LAS)) grown with 0 or 50 μM CdSO4. A total of 18.76 million clean reads from the soybean root samples were obtained after quality assessment and data filtering. After Cd treatment, 739 differentially expressed genes (DEGs; 265 up and 474 down) were found in HAS; however, only 259 DEGs (88 up and 171 down) were found in LAS, and 64 genes were same between the two varieties. Pathway enrichment analysis suggested that after cadmium treatment, the DEGs between LAS and HAS were mainly enriched in glutathione metabolism and plant-pathogen interaction pathways. KEGG analysis showed that phenylalanine metabolism responding to cadmium stress in LAS, while ABC transporters responding to cadmium stress in HAS. Besides we found more differential expressed heavy metal transporters such as ABC transporters and zinc transporters in HAS than LAS, and there were more transcription factors differently expressed in HAS than LAS after cadmium treatment in two soybean varieties, eg. bHLH transcription factor, WRKY transcription factor and ZIP transcription factor. Conclusions Findings from this study will shed new insights on the underlying molecular mechanisms behind the Cd accumulation in soybean.

In the process of high-speed additive manufacturing, machining defects such as low surface accuracy, high surface roughness, residual stresses and micro-cracks have a serious impact on the performance and life of the product. These machining defects need to be removed by post-treatment in order to promote the use of additive manufactured parts in industrial production. This article provides a systematic review of existing post-treatment technologies for additive manufactured parts, divided into surface post-treatment technologies and overall post-treatment technologies. The processing cost expenditure of the most common post-processing methods is analyzed. The core values and key metrics of post-processing are explored. The prospects for post-processing technology for additive manufactured parts in six key development directions are discussed. The present review systematically discusses the process capabilities and research developments of post-processing technologies for high-speed additive manufacturing, taking into account knowledge from both basic and applied research areas.

Background: Pollen exposure is an environmental risk factor for asthma symptoms and allergic reactions in children. The extent to which pollen exposure in pregnancy and the first year of life influences the development of childhood asthma and rhinitis is not fully understood. Objective: We aimed to investigate early life exposures to pollen with childhood asthma and rhinitis at age 6 in a longitudinal birth cohort of the United Kingdom. Methods: In this retrospective cohort study, via logistic regressions, we analyzed the associations between pollen exposures in pregnancy and the first year of life with childhood asthma and rhinitis. Results: Higher pollen exposure accumulated during pregnancy and during the first year of life both associated with an increased odds of asthma at age 6 (OR = 1.14, 95% CI 1.03–1.26, p = 0.01; OR = 1.15, 95% CI 1.03–1.29, p = 0.02, respectively). We did not observe statistically significant associations between early life pollen exposures and the odds of rhinitis at the same age. Conclusion: High pollen exposure during early life (prenatal and postnatal) associated with an increased risk of asthma incidence at age 6. Further studies are desired to validate these findings and to elucidate the mechanisms of early life exposures to pollen on asthma etiology.

With the rapid development of the Yangtze River Basin, the issue of underwater noise pollution has become increasingly severe, which has adversely affected aquatic creatures, particularly fish. Ecological fish-nest bricks (EFNBs), a new type of eco-friendly revetment, can provide a favorable habitat for fish. However, its effects on the acoustic environment remain unclear. The finite element numerical simulation method of acoustic-structure coupling is adopted to explore the acoustic environment of EFNBs, analyzing the impact of sound source frequency (within 300 Hz), structural forms, and arrangement of these bricks on the internal sound pressure level. The sound pressure level distribution of A-EFNBs were also analyzed at a distance of 0–0.5 m from the opening. A method of acoustic environment improvement is proposed, which utilizes porous polyurethane sponge (PPS) sound-absorbing material to establish a conducive acoustic environment for fish in EFNBs. The study results indicate that at low frequencies of sound source (f ≤ 150 Hz), the sound pressure level within EFNBs slightly decreases compared to the adjacent areas without EFNBs. The sound pressure level variation within the bricks increases with sound source frequency. The peak sound pressure increases with the number of openings. Interval arrangements can in general decrease sound pressure by less than 20 dB. At higher frequencies(f＞200 Hz), the sound pressure level at the opening of the A-EFNBs tends to increase. However, the PPS sound-absorbing material substantially reduces the sound pressure level by 15 –55 dB, rendering it an effective method for improving the acoustic environment for fish. The PPS sound-absorbing material is more suitable for habitat improvement of black carp (Mylopharyngodon piceus) and grass carp (Ctenopharyngodon idellus) with relatively low hearing thresholds among the four famous Chinese carps. The research findings can serve as a reference for designing and implementing river ecological restoration projects.

BackgroundQualitative myocardial perfusion (QMP) derived from myocardial contrast echocardiography reflects the capillary flow, while coronary flow velocity reserve from Doppler spectrum (D-CFVR) of the left anterior descending coronary artery (LAD) is used to assess coronary microvascular function, particularly after excluding severe epicardial coronary stenosis. The present study aimed to assess the relationship of QMP and D-CFVR in detecting coronary microvascular disease (CMVD) by using adenosine triphosphate stress myocardial contrast echocardiography (ATP stress MCE).Methods and resultsSeventy-two patients (mean age: 54.22 ± 12.78 years) with chest pain and

Shade has a direct impact on photosynthesis and production of plants. Exposure to shade significantly reduces crops yields. Identifying shade-tolerant genomic loci and soybean varieties is crucial for improving soybean yields. In this study, we applied a shade treatment (30% light reduction) to a natural soybean population consisting of 264 accessions, and measured several traits, including the first pod height, plant height, pod number per plant, grain weight per plant, branch number, and main stem node number. Additionally, we performed GWAS on these six traits with and without shade treatment, as well as on the shade tolerance coefficients (STCs) of the six traits. As a result, we identified five shade-tolerance varieties, 733 SNPs and four candidate genes over two years. Furthermore, we developed four kompetitive allele-specific PCR (KASP) makers for the STC of S18_1766721, S09_48870909, S19_49517336, S18_3429732. This study provides valuable genetic resources for breeding soybean shade tolerance and offers new insights into the theoretical research on soybean shade tolerance.

ObjectivesSpecialty nurses play a crucial role in specialized nursing practice, teaching, management, and research. These nurses often face significant work pressure; therefore, scientifically and effectively assessing their job stress and its sources is vital for enhancing the quality of their work. However, there is currently a dearth of verified assessment tools for measuring job stressors among specialty nurses. Therefore, this study aimed to develop and test an instrument to assess the job stressors applicable to specialty nurses.MethodsWe conducted a multiphase mixed-methods study. The initial scale items were developed from a literature review and structured interviews. The scale was then refined through two rounds of expert consultation (N = 14) and a primary test (N = 20). A main survey (N = 552) was then conducted to evaluate the scale’s construct validity and reliability using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA).ResultsThe final scale comprises four dimensions with 27 items. The factors included “specialized nursing and work,” “workload and time allocation,” “patient care,” and “work resources and environment.” The EFA explained 69.10% of the variance, while the CFA confirmed a good model fit. The content validity index was 0.980 at the scale level and 0.790–1.000 at the item level. The scale’s reliability was supported by its high Cronbach’s α (0.958), test–retest reliability (0.946), and split-half reliability (0.868).ConclusionOur findings indicate that the job stressor scale developed in this study is valid and reliable, and is recommended for use among specialty nurses to assess their stressors.

Objectives Specialty nurses play a significant role in improving patient care; however, little is known about the factors affecting their work engagement. This study aimed to explore the relationship between role stress and work engagement among specialty nurses in China.Design A descriptive, cross-sectional study was applied in this study.Setting The study was conducted in the Henan Provincial People’s Hospital in China.Participants From March to April 2023, we conducted a cross-sectional descriptive study, using convenience sampling to recruit 972 specialty nurses from 42 specialised fields in China.Methods An online questionnaire survey was conducted using the Basic Information Questionnaire, Role Stress Scale and Specialty Nurse Work Engagement Scale. The collected data were analysed by using SPSS 21.0 software. The differences in total work engagement scores between subgroups were investigated using a single-factor analysis of variance. A Spearman’s rank correlation and a Pearson’s correlation were used to determine the relationship between general information, role stress and work engagement. A ridge regression analysis explored the impact of role stress on work engagement.Results The total score of role stress was (52.44±19.92) and the total score of work engagement was (140.27±17.76). Among the scores of various dimensions of specialty nurses’ work engagement, the standardised score for work attitude was the highest (4.54±0.56), followed by work values (4.46±0.64); the standardised score of work enthusiasm and focus was the lowest (4.22±0.64). Additionally, role ambiguity (r=−0.352, p

Abstract Functional traits reflect plants' adaptability to their environment, and environmental gradients influence their distribution. But few studies have investigated the link between these traits and species substitution patterns or the relevant ecological factors. We measured the aboveground (leaf) and belowground (root) functional traits of Stipa species in 17 plots across natural grasslands in Ningxia in Northern China. Redundancy analysis was used to explore the relationships between Stipa's functional traits and its species substitution distribution. Then, on the species substitution gradient, principal component analysis (PCA) was used to verify and quantify the leaf economic spectrum (LES), root economic spectrum (RES), and whole‐plant economic spectrum (WPES), with the relation between these spectra investigated by fitting standardized major axis regressions. The effects of aboveground, belowground, and whole‐plant ecological factors were quantified and ranked by variance decomposition and hierarchical partitioning. Our results showed that functional traits drive the substitution distribution of Stipa species, in being variously coupled with its desert, typical, and meadow steppe habitat types. The leaf, root, and whole‐plant economic spectra of Stipa species in desert steppe exhibit a “quick investment‐acquisition” strategy. In typical steppe, the leaf and whole‐plant economic spectra of Stipa species correspond to a “fast investment‐acquisition” strategy, whereas the root economic spectrum adopts a “slow investment‐acquisition” strategy. On meadow steppe, the leaf, root, and whole‐plant economic spectra of Stipa species similarly adopt a “slow investment‐acquisition” strategy. Finally, when considering the environmental factors involved, we find that the substitution distribution of Stipa spp. is chiefly a response to shifting soil patterns, these mainly driven by soil total nitrogen and nitrogen/phosphorus ratio. Collectively, these findings provide an important reference for the ecological restoration and reconstruction of grassland ecosystems, to better understand the relationship between plant functional traits and ecological niche attributes, and thus guide the reasonable restoration of grassland vegetation.

Introduction There is a growing emphasis on the importance of the availability of specialist palliative care for people with motor neuron disease (MND). However, the palliative care needs of this population and the utilisation of different specialist services remain poorly defined.Objectives To (1) describe clinical characteristics, symptom burden and functional levels of patients dying with MND on their admission to palliative care services; (2) determine factors associated with receiving inpatient or community palliative care services.Design An observational study based on point-of-care assessment data from the Australian Palliative Care Outcomes Collaboration.Participants A total of 1308 patients who received palliative care principally because of MND between 1 January 2013 and 31 December 2020.Measures Five validated clinical instruments were used to assess each individual’s function, distress from symptoms, symptom severity and urgency and acuity of their condition.Results Most patients with MND had no or mild symptom distress, but experienced a high degree of functional impairment. Patients who required ‘two assistants for full care’ relative to those who were ‘independent’ (OR=11.53, 95% CI: 4.87 to 27.26) and those in ‘unstable’ relative to ‘stable’ palliative care phases (OR=16.74, 95% CI: 7.73 to 36.24) were more likely to use inpatient versus community-based palliative care. Associations between the use of different palliative care services and levels of symptom distress were not observed in this study.Conclusions Patients with MND were more likely to need assistance for decreased function and activities of daily living, rather than symptom management. This population could have potentially been cared for in the palliative phase in a community setting if greater access to supportive services were available in this context.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Background and purpose: GLP-1 receptor agonists are clinically utilized for type 2 diabetes and obesity. In vitro and in vivo preclinical studies were performed to assess the druggability of a novel small molecule GLP-1 receptor biased agonist SAL0112. Experimental approach: The HTRF assay, FLIPR assay, TR-FRET assay, and PathHunter assay were utilized for in vitro studies. Liver transporter tests were conducted using the HEK293-OATP1B1 and HEK293-OATP1B3 cell lines. In vitro stability assessments of various species and in vivo PK studies in rodents were performed. A model of type 2 diabetes and obesity induced by a high-energy diet in transgenic C57BL/6 mice expressing the human GLP-1 receptor gene was conducted. Principal results: SAL0112 demonstrated high potency and selectivity in activating the Gαs pathway of the GLP-1 receptor, with no observed desensitization. SAL0112 demonstrated greater stability in human and rat liver microsomes compared to Danuglipron. In vivo PK studies revealed higher absorption of SAL0112 in rats. SAL0112 displayed a significantly lower potential for DDI on liver transporters compared to Danuglipron. SAL0112 led to significant reductions in body weight (P

Abstract. Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

BackgroundSleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. ObjectiveTo evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. MethodsThis study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. ResultsThe median (P25, P75) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L−1] was higher than that in the control group [54.33 (24.86, 97.97) μg·L−1]. Additionally, the PSQI score (\begin{document}$ \overline{x}\pm {s} $\end{document}) in the exposure group (5.16±3.84) was higher than that in the control group (4.60±3.17). The multiple linear regression revealed that an increase in the sum of the concentrations of eight OH-PAHs after natural logarithmic transformation (lnΣ8OH-PAHs) was associated with an increase of 0.3646 (95%CI: 0.1337, 0.5955) in PSQI score, and an increase in lnΣlow-ring OH-PAHs was associated with an increase of 0.2954 (95%CI: 0.0941, 0.4967) in PSQI score. The BKMR analysis demonstrated that PSQI score was gradually increased as the increasing of lnΣ8OH-PAHs concentration. The quantile g-computation analysis indicated that a quantile increase in lnΣ8OH-PAHs concentration was associated with an increase of 0.4062% (95%CI: 0.1176%, 0.6949%) in PSQI score. ConclusionCompared to the controls, the coking workers show a higher concentration of urinary OH-PAHs and report worse sleep quality. The concentration of OH-PAHs is significantly negatively associated with sleep quality.

Objective:. Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods:. A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results:. The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion:. This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Abstract Background Newly recruited nurses face multiple sources of stress and their coping styles need to be focused on to ensure good mental health. This study aimed to examine the relationship among mental health literacy, psychological capital and coping styles in newly recruited nurses. Methods A cross-sectional study was conducted in August and September 2022. A total of 315 newly recruited nurses were recruited in a tertiary hospital in Henan Province, central China, employing the convenience sampling method. The self-reported questionnaires were sent through a QR code, including the Mental Health Literacy Scale for Healthcare Students, Psychological Capital Questionnaire, and Simplified Coping Style Questionnaire. Pearson correlation analysis was used to evaluate the relationships among the variables. Mediation analysis was performed to identify the mediating effect of psychological capital on the relationship between mental health literacy and coping styles. Results Positive coping showed a positive relationship with psychological capital and mental health literacy, while negative coping showed a negative relationship with psychological capital and mental health literacy. For positive coping, psychological capital was a partial mediator with an effect of 0.140, accounting for 62.8%. For negative coping, a full mediating effect was shown by psychological capital between mental health literacy and negative coping, with an indirect effect of -0.048. Conclusion Psychological capital plays a partial and complete mediating role between mental health literacy and different coping styles among newly recruited nurses. Diversified training and personalized guidance in improving mental health literacy and increasing psychological capital simultaneously can be provided to newly recruited nurses continuously to adjust their coping styles.

Abstract Background The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience. Methods A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed. Results Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (P

Abstract Background DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying these differentially methylated CpG regions (DMRs) associated with the phenotypes contributes to disease prediction and precision medicine development. Results We propose a novel DMR detection algorithm, gbdmr. In contrast to existing methods under a linear regression framework, gbdmr assumes that DNA methylation levels follow a generalized beta distribution. We compare gbdmr to alternative approaches via simulations and real data analyses, including dmrff, a new DMR detection approach that shows promising performance among competitors, and the traditional EWAS that focuses on single CpG sites. Our simulations demonstrate that gbdmr is superior to the other two when the correlation between neighboring CpG sites is strong, while dmrff shows a higher power when the correlation is weak. We provide an explanation of these phenomena from a theoretical perspective. We further applied the three methods to multiple real DNA methylation datasets. One is from a birth cohort study undertaken on the Isle of Wight, United Kingdom, and the other two are from the Gene Expression Omnibus database repository. Overall, gbdmr identifies more DMR CpGs linked to phenotypes than dmrff, and the simulated results support the findings. Conclusions Gbdmr is an innovative method for detecting DMRs based on generalized beta regression. It demonstrated notable advantages over dmrff and traditional EWAS, particularly when adjacent CpGs exhibited moderate to strong correlations. Our real data analyses and simulated findings highlight the reliability of gbdmr as a robust DMR detection tool. The gbdmr approach is accessible and implemented by R on GitHub: https://github.com/chengzhouwu/gbdmr .

Abstract Optimizing resource allocation and routing to satisfy service needs is paramount in large-scale networks. Software-defined networking (SDN) is a new network paradigm that decouples forwarding and control, enabling dynamic management and configuration through programming, which provides the possibility for deploying intelligent control algorithms (such as deep reinforcement learning algorithms) to solve network routing optimization problems in the network. Although these intelligent-based network routing optimization schemes can capture network state characteristics, they are prone to falling into local optima, resulting in poor convergence performance. In order to address this issue, this paper proposes an African Vulture Routing Optimization (AVRO) algorithm for achieving SDN routing optimization. AVRO is based on the African Vulture Optimization Algorithm (AVOA), a population-based metaheuristic intelligent optimization algorithm with global optimization ability and fast convergence speed advantages. First, we improve the population initialization method of the AVOA algorithm according to the characteristics of the network routing problem to enhance the algorithm’s perception capability towards network topology. Subsequently, we add an optimization phase to strengthen the development of the AVOA algorithm and achieve stable convergence effects. Finally, we model the network environment, define the network optimization objective, and perform comparative experiments with the baseline algorithms. The experimental results demonstrate that the routing algorithm has better network awareness, with a performance improvement of 16.9% compared to deep reinforcement learning algorithms and 71.8% compared to traditional routing schemes.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.

Background Vorinostat (SAHA) is a histone deacetylase inhibitor that has shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, only a subset of patients with CTCL (30–35%) respond to SAHA and the response is not always sustainable. Thus, understanding the mechanisms underlying evasive resistance in this cancer is an unmet medical need to improve the efficacy of current therapies.Purpose This study aims to identify factors contributing to resistance against SAHA in CTCL and ways to mitigate it.Methods and results In this study, we demonstrated that attenuated reactive oxygen species (ROS) induces the expression of interleukin (IL)-2Rα, one of the IL-2 receptors, which drives resistance to SAHA in CTCL. We also determined that cantharidin could overcome SAHA resistance to CTCL by blocking IL-2Rα-related signaling via ROS-dependent manner. Mechanistically, accelerated translation of IL-2Rα contributes to excessive IL-2Rα protein formation as a result of reduced ROS levels in SAHA-resistant CTCL. At the same time, amplified IL-2R signals are evidenced by strengthened interaction of IL-2Rβ with IL-2Rγ and Janus kinase/signal transducer and activator of transcription molecules, and by increased expression of protein kinase B (AKT)/mTOR and mitogen-activated protein kinase signaling. Moreover, cantharidin, an active constituent of Mylabris used in traditional Chinese medicine, markedly increased ROS levels, and thereby restrained IL-2Rα translation, resulting in suppression of downstream pathways in SAHA-resistant cells. Cantharidin is also found to synergize with SAHA and triggers SAHA-resistant cell death via IL-2R signaling both in vitro and in vivo.Conclusion Our study uncovers a novel molecular mechanism of acquired SAHA resistance and also suggests that using cantharidin is a potential approach to overcome CTCL therapy resistance. Our findings underlie the therapeutic potential of cantharidin in treating CTCL.

BackgroundSnijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in CHD3 gene. There is limited information on SNIBCPS and few studies on its pathogenic gene CHD3.MethodsWe utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords “Snijders Blok-Campeau syndrome,” “CHD3,” or “SNIBCPS” to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS.ResultsWe identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function.ConclusionOur findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.

The incorporation of steel fibers in concrete imparts strain-hardening characteristics, significantly elevating the tensile toughness of the concrete mixture. However, this enhancement often comes at the expense of reduced workability and strength, posing challenges in achieving optimal densification in practical engineering applications. Moreover, the improvement of the performance of steel fiber-reinforced concrete (SFRC) hinges on the establishment of interfacial transition zone (ITZ) between steel fibers and the concrete paste. It has been established that the introduction of fly ash and silica fume to concrete mixtures can increase fluidity and strength. Consequently, this study investigates the impact of fly ash and silica fume on the performance enhancement and workability of SFRC mixtures, scrutinizing both macroscopic and microscopic aspects. Two sets of high-flowable steel fiber-reinforced concretes (HF-SFRC) incorporating silica fume or fly ash were prepared and subjected to testing. The assessment covered mechanical properties, including compressive strength, compressive toughness, and flexural toughness, along with the microstructure. The microstructure provides evidence that fly ash and silica fume reduced the voids in the concrete matrix to different degrees and that the fully hydrated dense matrix contributed to reinforcing the bond between steel fibers and the cement matrix. The synergistic effect among fly ash or silica fume, steel fibers, and cement in the mixture resulted in enhanced flowability and improved mechanical properties in HF-SFRC.

Washed red blood cells (RBCs) can be used to treat immune-related diseases. However, whether the washing process changes the quality of RBCs and affects the curative effect of transfusion therapy remains unclear. We retrospectively analysed the clinical data of patients who received blood transfusion. The physiological and biochemical parameters of RBCs were tested on an automated haematology-biochemical analyser. CD47 and phosphatidylserine (PS) plasma membrane expression were analysed using flow cytometry. Morphological changes in RBCs were observed using scanning electron microscopy. The results showed that the curative effect on patients who received washed RBCs was weaker than that on those who received non-washed RBCs. Physiological and biochemical parameters of RBCs were not significantly different. RBC immune indices changed significantly after washing. The expression of “don't eat me” signals was weakened, whereas the intensity of “eat me” signals was enhanced. This study suggests that the current use of physiological and biochemical parameters as indicators to evaluate the quality of RBCs may not be comprehensive and that evaluation of the real status of RBCs requires other effective parameters. Immune molecules in RBCs are expected to become supplementary markers for evaluating RBC quality.

Epigenetic mechanisms are involved in several cellular functions, and their role in the immune system is of prime importance. Histone deacetylases (HDACs) are an important set of enzymes that regulate and catalyze the deacetylation process. HDACs have been proven beneficial targets for improving the efficacy of immunotherapies. HDAC11 is an enzyme involved in the negative regulation of T cell functions. Here, we investigated the potential of HDAC11 downregulation using RNA interference in CAR-T cells to improve immunotherapeutic outcomes against prostate cancer. We designed and tested four distinct short hairpin RNA (shRNA) sequences targeting HDAC11 to identify the most effective one for subsequent analyses. HDAC11-deficient CAR-T cells (shD-NKG2D-CAR-T) displayed better cytotoxicity than wild-type CAR-T cells against prostate cancer cell lines. This effect was attributed to enhanced activation, degranulation, and cytokine release ability of shD-NKG2D-CAR-T when co-cultured with prostate cancer cell lines. Our findings reveal that HDAC11 interference significantly enhances CAR-T cell proliferation, diminishes exhaustion markers PD-1 and TIM3, and promotes the formation of T central memory TCM populations. Further exploration into the underlying molecular mechanisms reveals increased expression of transcription factor Eomes, providing insight into the regulation of CAR-T cell differentiation. Finally, the shD-NKG2D-CAR-T cells provided efficient tumor control leading to improved survival of tumor-bearing mice in vivo as compared to their wild-type counterparts. The current study highlights the potential of HDAC11 downregulation in improving CAR-T cell therapy. The study will pave the way for further investigations focused on understanding and exploiting epigenetic mechanisms for immunotherapeutic outcomes.

Lung cancer is the leading cause of cancer-related deaths worldwide. Bone is a common metastatic site of lung cancer, about 50% of bone metastatic patients will experience skeletal related events (SREs). SREs not only seriously impact the quality of life of patients, but also shorten their survival time. The treatment of bone metastasis requires multi-disciplinary therapy (MDT) and development of individualized treatment plan. In order to standardize the diagnosis and treatment of bone metastasis in lung cancer, the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract Aims To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). Materials and methods In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. Results Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12–2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13–4.44; p = 0.033). Conclusion In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Abstract Background and objective Although chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD. Methods We identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups. Results We collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50–59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading. Conclusion A screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.

Abstract Background Domestic goose breeds are descended from either the Swan goose (Anser cygnoides) or the Greylag goose (Anser anser), exhibiting variations in body size, reproductive performance, egg production, feather color, and other phenotypic traits. Constructing a pan-genome facilitates a thorough identification of genetic variations, thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic variability. Results To comprehensively facilitate population genomic and pan-genomic analyses in geese, we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq samples. By constructing the pan-genome for geese, we generated non-reference contigs totaling 612 Mb, unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes, 1,324 softcore genes, 2,734 shell genes, and 878 cloud genes in goose genomes. Furthermore, we detected an 81.97 Mb genomic region showing signs of genome selection, encompassing the TGFBR2 gene correlated with variations in body weight among geese. Genome-wide association studies utilizing single nucleotide polymorphisms (SNPs) and presence-absence variation revealed significant genomic associations with various goose meat quality, reproductive, and body composition traits. For instance, a gene encoding the SVEP1 protein was linked to carcass oblique length, and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique length. Notably, the pan-genome analysis revealed enrichment of variable genes in the “hair follicle maturation” Gene Ontology term, potentially linked to the selection of feather-related traits in geese. A gene presence-absence variation analysis suggested a reduced frequency of genes associated with “regulation of heart contraction” in domesticated geese compared to their wild counterparts. Our study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple organs and tissues in geese and analyzing population variation. Conclusion This accomplishment originates from the discernment of a multitude of selection signals and candidate genes associated with a wide array of traits, thereby markedly enhancing our understanding of the processes underlying domestication and breeding in geese. Moreover, assembling the pan-genome for geese has yielded a comprehensive apprehension of the goose genome, establishing it as an indispensable asset poised to offer innovative viewpoints and make substantial contributions to future geese breeding initiatives.

Objective A micro‐electromechanical system (MEMS) was developed based on spatial alignment and navigation technology to assist femoral extramedullary alignment osteotomy (FEAO) in total knee arthroplasty (TKA). The system can locate and adjust the femoral distal condylar osteotomy (FDCO) to obtain a better femoral prosthesis placement. It is a portable navigation device and provides an innovative approach for FDCO. Methods Sixty patients who suffered from severe knee osteoarthritis who underwent unilateral TKA from May 14, 2021 to May 30, 2022 were randomly divided into a MEMS‐FEAO group and a conventional femoral intramedullary alignment osteotomy (FIAO) group, with 30 cases in each group for a controlled retrospective study. The hip‐knee‐ankle angle (HKAA) of the lower limb was measured before and after surgery, the femoral valgus angle (FVA) was measured preoperatively, and the femoral prosthesis valgus angle (FPVA) and the femoral prosthesis flexion angle (FPFA) were measured postoperatively following computed tomography imaging protocols. Measurement data is statistically described as mean ± standard deviation c. The count data is described by frequency (constituent ratio) using the rank sum test. Result A total of 6.7% (2/30) of FEAO compared to 20.0% (6/30) of FIAO cases were postoperative deviations where the HKAA exceeded ±3° of neutral alignment (p 0.05), and there was no statistical significance between the two groups. Conclusion The MEMS‐FEAO system can improve the accurate alignment and can be utilized as a locator to obtain the best femoral prosthesis placement in TKA and significantly reduce the rate of poor force line of the lower limb.

This paper introduces fractional Brownian motion into the study of Maxwell nanofluids over a stretching surface. Nonlinear coupled spatial fractional-order energy and mass equations are established and solved numerically by the finite difference method with Newton’s iterative technique. The quantities of physical interest are graphically presented and discussed in detail. It is found that the modified model with fractional Brownian motion is more capable of explaining the thermal conductivity enhancement. The results indicate that a reduction in the fractional parameter leads to thinner thermal and concentration boundary layers, accompanied by higher local Nusselt and Sherwood numbers. Consequently, the introduction of a fractional Brownian model not only enriches our comprehension of the thermal conductivity enhancement phenomenon but also amplifies the efficacy of heat and mass transfer within Maxwell nanofluids. This achievement demonstrates practical application potential in optimizing the efficiency of fluid heating and cooling processes, underscoring its importance in the realm of thermal management and energy conservation.

Two-dimensional (2D) metallic transition metal dichalcogenides (TMDs) have garnered significant attention as promising candidates for various applications, including electronics, spintronics, and energy-related fields. Their appeal lies in their exceptional electronic conductivity, room-temperature ferromagnetism, charge density wave (CDW) phenomena, and catalytic properties, among other attributes. Among the diverse array of metallic TMDs, vanadium dichalcogenides (VX2, X = S, Se, and Te) stand out due to their distinctive set of physical and chemical properties. These properties have positioned VX2 materials at the forefront of both fundamental research and technological exploration in fields such as condensed matter physics, materials science, and device physics. In this comprehensive review, we present a thorough investigation of the recent advancements in 2D metallic VX2 materials and related heterostructures in the aspects of their structures, fabrication methods, key properties, and potential applications. First, the electronic and crystal structures of 2D VX2 are introduced. Second, the growth methods of VX2 and their heterostructures are discussed. Then, the novel physical properties and potential applications of 2D VX2 and its heterostructures are highlighted. Finally, we assess the current state of development in this growing field, acknowledging the obstacles ahead and the promising avenues for future research.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.