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Objective Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. Methods Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. Results In OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85). Conclusion Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

As the rate of population aging accelerates, the prevalence of stroke among the older population continues to rise. Elderly stroke patients have a high prevalence of neurological impairment, severe clinical manifestations, many associated comorbidities, unfavorable prognosis, prolonged rehabilitation duration, and need extended caregiver support. Elderly stroke patients have challenges in accessing necessary long-term care services due to several circumstances, resulting in notable issues in long-term care. This paper examines the clinical features of elderly stroke patients and presents an overview of long-term care both domestically and internationally. It discusses the current issues surrounding long-term care in our country, focusing on three different forms of care. The paper proposes countermeasures to address these problems, considering the roles of the government, society, medical professionals, institutions, families, and individuals. The aim is to offer guidance for enhancing the quality of long-term care.

Abstract Breast tumor‐initiating cells (BTICs) of triple‐negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin‐α dependent manner. Nuclear SOSTDC1 interacts with the N‐terminus of the nucleoprotein, chromatin helicase DNA‐binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to β‐transducin repeat‐containing protein (β‐TrCP) binding motifs of CHD1 is found, thereby blocking the β‐TrCP‐CHD1 interaction and inhibiting β‐TrCP‐mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies.

Abstract Conductive‐bridge random access memory (CBRAM) emerges as a promising candidate for next‐generation memory and storage device. However, CBRAMs are prone to degenerate and fail during electrochemical metallization processes. To address this issue, herein we propose a self‐repairability strategy for CBRAMs. Amorphous NbSe2 was designed as the resistive switching layer, with Cu and Au as the top and bottom electrodes, respectively. The NbSe2 CBRAMs demonstrate exceptional cycle‐to‐cycle and device‐to‐device uniformity, with forming‐free and compliance current‐free resistive switching characteristics, low‐operation voltage, and competitive endurance and retention performance. Most importantly, the self‐repairable behavior is discovered for the first time in CBRAM. The device after failure can recover its performance to the initially normal state by operating with a slightly large reset voltage. The existence of Cu conductive filament and excellent controllability of Cu migration in the NbSe2 switching layer has been revealed by a designed broken‐down point approach, which is responsible for the self‐repairable behavior of NbSe2 CBRAMs. Our self‐repairable and high‐uniform amorphous NbSe2 CBRAM may open the door to the development of memory and storage devices in the future.

Four new diterpenoids, isodosins A–D (1–4), together with nine known compounds (5–13) were isolated and identified from the aerial parts of Isodon serra (Maxim.) Hara. The structures of the new diterpenoids were elucidated based on the analysis of HR-ESI-MS data, 1D/2D-NMR-spectroscopic data, and electronic circular dichroism (ECD) calculations. Cytotoxicities of compounds 2, 3, 5, 6, and 9 against the HepG2 and H1975 cell lines were evaluated with the MTT assay. As a result, compounds 2, 3, and 6 revealed higher levels of cytotoxicity against HepG2 cells than against H1975 cells. Moreover, compund 6 demonstrated the most efficacy in inhibiting the proliferation of HepG2 cells, with an IC50 value of 41.13 ± 3.49 μM. This effect was achieved by inducing apoptosis in a dose-dependent manner. Furthermore, the relationships between the structures and activities of these compounds are briefly discussed.

Abstract The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation of endogenous and exogenous aldehydes to carboxylic acids, which contributes to cellular and tissue homeostasis. ALDHs play essential parts in detoxification, biosynthesis, and antioxidants, which are of important value for cell proliferation, differentiation, and survival in normal body tissues. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Notably, the involvement of the ALDHs in tumor progression is responsible for the maintenance of the stem‐cell‐like phenotype, triggering rapid and aggressive clinical progressions. ALDHs have captured increasing attention as biomarkers for disease diagnosis and prognosis. Nevertheless, these require further longitudinal clinical studies in large populations for broad application. This review summarizes our current knowledge regarding ALDHs as potential biomarkers in tumors and several non‐tumor diseases, as well as recent advances in our understanding of the functions and underlying molecular mechanisms of ALDHs in disease development. Finally, we discuss the therapeutic potential of ALDHs in diseases, especially in tumor therapy with an emphasis on their clinical implications.

BackgroundsAs a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high.MethodsData were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs.ResultsA total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1β) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP.ConclusionsWe identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.

Abstract Background The UDP-glucuronosyltransferase 91D2 (SrUGT91D2) gene is a crucial element in the biosynthetic pathway of steviol glycosides (SGs) and is responsible for creating 1,2-β-D glucosidic bonds at the C19 and C13 positions. This process plays a vital role in the synthesis of rebaudioside M (RM) and rebaudioside D (RD). The promoter, which regulates gene expression, requires functional analysis to understand gene expression regulation. However, investigations into the function of the promoter of SrUGT91D2 (pSrUGT91D2) have not been reported. Results The pSrUGT91D2 was isolated from six S. rebaudiana lines, and subsequent multiple sequence comparisons revealed the presence of a 26 bp inDel fragment (pSrUGT91D2-B1188 type) in lines GP, GX, 110, 1114, and B1188 but not in the pSrUGT91D2 of line 023 (pSrUGT91D2-023 type). Bioinformatics analysis revealed a prevalence of significant cis-regulatory elements (CREs) within the promoter sequences, including those responsive to abscisic acid, light, anaerobic conditions, auxin, drought, low temperature, and MeJA. To verify the activity of pSrUGT91D2, the full-length promoter and a series of 5’ deletion fragments (P1–P7) and a 3’ deletion fragment (P8) from various lines were fused with the reporter β-glucuronidase (GUS) gene to construct the plant expression vector, pCAMBIA1300-pro∷GUS. The transcriptional activity of these genes was examined in tobacco leaves through transient transformation. GUS tissue staining analysis and enzyme activity assays demonstrated that both the full-length promoter and truncated pSrUGT91D2 were capable of initiating GUS expression in tobacco leaves. Interestingly, P8-pSrUGT91D2-B1188 (containing the inDel segment, 301 bp) exhibited enhanced activity in driving GUS gene expression. Transient expression studies of P8-pSrUGT91D2-B1188 and P8-pSrUGT91D2-023 in response to exogenous hormones (abscisic acid and indole-3-acetic acid) and light indicated the necessity of the inDel region for P8 to exhibit transcriptional activity, as it displayed strong responsiveness to abscisic acid (ABA), indole-3-acetic acid (IAA), and light induction. Conclusions These findings contribute to a deeper understanding of the regulatory mechanism of the upstream region of the SrUGT91D2 gene and provide a theoretical basis for future studies on the interaction between CREs of pSrUGT91D2 and related transcription factors.

Abstract Objective To analyze the influential factors of frailty in elderly patients with coronary heart disease (CHD), develop a nomogram-based risk prediction model for this population, and validate its predictive performance. Methods A total of 592 elderly patients with CHD were conveniently selected and enrolled from 3 tertiary hospitals, 5 secondary hospitals, and 3 community health service centers in China between October 2022 and January 2023. Data collection involved the use of the general information questionnaire, the Frail scale, and the instrumental ability of daily living assessment scale. And the patients were categorized into two groups based on frailty, and χ2 test as well as logistic regression analysis were used to identify and determine the influencing factors of frailty. The nomograph prediction model for elderly patients with CHD was developed using R software (version 4.2.2). The Hosmer–Lemeshow test and the area under the receiver operating characteristic (ROC) curve were employed to assess the predictive performance of the model. Additionally, the Bootstrap resampling method was utilized to validate the model and generate the calibration curve of the prediction model. Results The prevalence of frailty in elderly patients with CHD was 30.07%. The multiple factor analysis revealed that poor health status (OR = 28.169)/general health status (OR = 18.120), age (OR = 1.046), social activities (OR = 0.673), impaired instrumental ability of daily living (OR = 2.384) were independent risk factors for frailty (all P

Abstract Semiconductor‐based photoelectrochemical (PEC) organic transformations usually show radical characteristics, in which the reaction selectivity is often difficult to precisely control due to the nonselectivity of radicals. Accordingly, several simple organic reactions (e.g., oxidations of alcohols, aldehydes, and other small molecules) have been widely studied, while more complicated processes like C─C coupling remain challenging. Herein, a synergistic heterogeneous/homogeneous PEC strategy is developed to achieve a controllable radical‐induced C─C coupling reaction mediated by the copper‐coordination effect at the semiconductor/electrolyte interfaces, which additionally exerts a significant impact on the product regioselectivity. Through experimental studies and theoretical simulations, this study reveals that the copper‐chloride complex effectively regulates the formation of chloride radicals, a typical hydrogen atom transfer agent, on semiconductor surfaces and stabilizes the heterogeneous interfaces by suppressing the radical‐induced surface passivation. Taking the Minisci reaction (the coupling between 2‐phenylquinoline and cyclohexane) as a model, the yield of the target C─C coupling product reaches up to 90% on TiO2 photoanodes with a selectivity of 95% and long‐term stability over 100 h. Moreover, such a strategy exhibits a broad scope and can be used for the functionalization of various heteroaromatic hydrocarbons.

ObjectiveThe purpose of this study is to examine the changes in supportive care needs, quality of life and social support during different chemotherapy cycles among elderly colorectal cancer patients.MethodsThis prospective longitudinal study recruited 160 elderly colorectal cancer patients using convenience sampling at a hospital in Guangxi between August 2023 and April 2024. To assess supportive care needs, quality of life, and social support, we used a short form of the Supportive Care Needs Survey (SCNS-SF34), a Functional Assessment of Cancer Therapy-colorectal (FACT-C), and a perceived social support scale (PSSS) prior to chemotherapy, as well as after the first, third, and sixth cycles. Repeated measures analysis of variance was used to validate the changes over time in supportive care needs, quality of life, and social support.Results155 participants completed all questionnaire sessions across the six cycles. From pre-chemotherapy until after the sixth cycle of chemotherapy, the extent of physical and daily living requirements among all respondents fluctuated between 47.23% and 88.26%, psychological needs ranged from 60.84% to 97.67%, patient care and support needs ranged from 83.75% to 99.35%, healthcare system and information needs varied from 85.98% to 99.00%, while the level of sexual needs decreased from 1.51% to 0.65%. The mean SCNS-SF34 scores for these participants ranged between 103.81 ± 2.28 and 144.10 ± 1.08. Significant increases over time were seen for all domains of SCNS-SF34 (F=126.99, 347.41, 65.00, 72.34, 160.15, p

Background: Approximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Abstract Background Ralstonia pickettii is a low virulent, gram-negative bacillus that is rarely associated with human infections and may cause bacteremia. Microbacterium species are gram-positive coryneforms that are generally considered as a contaminant in Gram staining of blood cultures, especially when the time to positivity is longer than 48 h. Both these bacterial species are emerging opportunistic pathogens that may occasionally cause serious infections and even life-threatening health conditions. Case presentation Here, we report the case of a patient with bacteremia caused by both R. pickettii and Microbacterium. We advocate for providers to order rapid antibiotic susceptibility testing, since our patient’s suffered two kinds of rare pathogens with the opposite of drug sensitivity results to imipenem. Conclusions Our case present a patient suffered septic shock caused by R. pickettii and Microbacterium. Improving the antibiotic management based on the result of antimicrobial susceptibility tests is the key of successful treatment.

A large amount of waste slurry water will be generated in the production process of concrete mixing plant, due to the complex composition of waste slurry water, if it is not handled in time when stored, serious coagulation will occur, which will accelerate the loss of equipment and reduce the utilization rate. In this paper, a super retarder suitable for waste slurry recycled water from concrete mixing plant was prepared using composite technology. The waste slurry recycled water mixed with super retarding agent was characterized by using microscopic testing means XRD, TG and DTG. The waste slurry recycled water mixed with super retarding agent was used to replace tap water in the production of concrete, and its effect on the workability and mechanical properties of concrete was investigated. It was found that the compounding of Butane 2-phospho-1,2,4-tricarboxylic acid (PBTCA) with Reclaimed water treatment agent (ACS) resulted in a setting time of 64 h for 10% concentration of recycled water, with optimal retarding effect. When PBTCA:ACS was 1:20, mixed at 1.5% of the mass of recycled water, the 1 h slump of concrete had no loss, the loss of extension was 15 mm, the 7 days compressive strength was increased by 3.5 MPa, and the 28 days compressive strength was increased by 3.0 MPa. The microscopic results showed that the use of ACS and PBTCA does not affect the type of cement hydration products, but only affects the the rate of hydration product generation.

BackgroundTo date, more than 770 million individuals have become coronavirus disease 2019 (COVID-19) convalescents worldwide. Emerging evidence highlights the influence of COVID-19 on the oral microbiome during both acute and convalescent disease phases. Front-line healthcare workers are at an elevated risk of exposure to viral infections, and the effects of COVID-19 on their oral microbiome remain relatively unexplored.MethodsOropharyngeal swab specimens, collected one month after a negative COVID-19 test from a cohort comprising 55 healthcare workers, underwent 16S rRNA sequencing. We conducted a comparative analysis between this post-COVID-19 cohort and the pre-infection dataset from the same participants. Community composition analysis, indicator species analysis, alpha diversity assessment, beta diversity exploration, and functional prediction were evaluated.ResultsThe Shannon and Simpson indexes of the oral microbial community declined significantly in the post-COVID-19 group when compared with the pre-infection cohort. Moreover, there was clear intergroup clustering between the two groups. In the post-COVID-19 group, the phylum Firmicutes showed a significant increase. Further, there were clear differences in relative abundance of several bacterial genera in contrast with the pre-infection group, including Streptococcus, Gemella, Granulicatella, Capnocytophaga, Leptotrichia, Fusobacterium, and Prevotella. We identified Gemella enrichment in the post-COVID-19 group, potentially serving as a recovery period performance indicator. Functional prediction revealed lipopolysaccharide biosynthesis downregulation in the post-COVID-19 group, an outcome with host inflammatory response modulation and innate defence mechanism implications.ConclusionDuring the recovery phase of COVID-19, the oral microbiome diversity of front-line healthcare workers failed to fully return to its pre-infection state. Despite the negative COVID-19 test result one month later, notable disparities persisted in the composition and functional attributes of the oral microbiota.

The precise expression of transcription factors (TFs) is crucial for plant growth and development, especially during somatic embryogenesis. However, conventional overexpression approaches, commonly used for functional genetics, can lead to deleterious effects. Therefore, it is imperative to ensure that TFs are expressed in a controlled and timely manner when aiming to enhance the efficiency of somatic embryogenesis. In this study, a dexamethasone/glucocorticoid receptor (DEX/GR) inducible expression system was employed to modulate the protein expression levels of target TFs within the nucleus during somatic embryogenesis in Liriodendron hybrids. We selected the WUSCHEL (WUS) gene, a well-established functional TF known for its vital role in somatic embryogenesis, as a model to assess the effectiveness of this system. Through DEX treatment, we induced the translocation of LhWUS-GR/LhWUS-GFP-GR fusion proteins from the cytoplasm to the nucleus, consequently leading to WUS-driven somatic embryogenesis. As the DEX concentration increased, there was a corresponding increase in the migration of the LhWUS-GFP-GR fusion protein into the nucleus. Additionally, we observed a higher proliferation ratio of callus expressing LhWUS-GR when exposed to varying DEX concentrations. Notably, the efficiency of somatic embryogenesis exhibited significant improvement under optimal DEX concentration. In conclusion, our study successfully utilizes the DEX/GR inducible system in Liriodendron hybrids, offering a valuable tool for the precise control and utilization of TFs at the desired levels. This innovative approach holds promise for advancing our understanding of TF function and enhancing plant development through the regulated manipulation of TF expression.

The meshless generalized finite difference method (GFDM) was used to simulate elastic wave propagation in the frequency domain. Dispersion analysis and numerical experiments were conducted to evaluate its performance. The dispersion analysis revealed that the GFDM requires approximately 5.6 grid points in a shear wavelength to suppress the dispersion error of 1% with a regular node distribution. To handle the artificial boundary reflection problem, a multiaxial convolutional perfectly matched layer (MCPML) was introduced to the meshless numerical simulation for its good performance. Numerical experiments showed that the meshless GFDM could effectively avoid stepped diffraction and reduce the total number of nodes for the calculation, by adopting an adaptive node distribution according to the model parameters. Compared to the 25-points finite difference method (FDM), the proposed method demonstrated high calculation accuracy, less memory consumption, and good boundary absorption effect, making it a reliable approach for elastic wave simulation in the frequency domain.

Abstract To explore the interaction of instrumental activities of daily living (IADLs) and dual sensory function on cognition in the elderly. A cross‐sectional survey was conducted in six general hospitals in China, from October 2022 to December 2022. Data collection included general information, IADLs scale, self‐reported sensory function questionnaire, and mini‐mental state examination (MMSE). Binary logistic regression was used to examine the association between factors and cognition. The interactive effect was evaluated by synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (AP). The odds ratio (OR) of IADLs decline in cognition is 4.412 (95% confidence interval [CI]: 3.633–5.358, p