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Abstract Background Bioterrorism is an important topic in the field of biosecurity. Nurses, the largest group of healthcare workers, play a critical role in addressing the threat of bioterrorism. This study aimed to examine the present level of bioterrorism knowledge, attitudes, and practices among nurses. It also explored the relationships among bioterrorism knowledge, attitudes, and practices, as well as demographic variables that influence the scores of each dimension. Methods A descriptive correlational research design was conducted using a convenience sample of 429 nurses in five tertiary general hospitals in Tianjin. Registered nurses with six months or more of work experience, currently still working in hospitals, and volunteering to participate in the study are included; otherwise, they are excluded. A structured questionnaire with four components was used: sociodemographic characteristics, knowledge of bioterrorism, attitudes toward bioterrorism, and practices related to bioterrorism. The acquired data were analyzed using the Mann‒Whitney test, Kruskal‒Wallis test, Spearman correlation analysis, and multiple linear regression. This study followed the STROBE guidelines. Results The study ultimately included 429 valid surveys. The mean score for bioterrorism knowledge was satisfactory (33.06 ± 4.87), the mean score for bioterrorism attitudes was good (23.83 ± 5.23), and the mean score for bioterrorism practices was poor (10.94 ± 6.51). There was a significant negative correlation between bioterrorism knowledge and attitudes (r=-0.38, p

Abstract This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway.

Abstract Background Breast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway. Results It was demonstrated that ZFP64 was overexpressed in BC specimens compared to adjacent normal tissues, and patients with high ZFP64 expression had shorter overall survival and disease-free survival. The analysis of the association of ZFP64 expression with clinicopathological characteristics showed that high ZFP64 expression is closely associated with N stage, TNM stage, and progesterone receptor status. Knockdown of ZFP64 suppressed the viability and colony formation capacity of BC cells by CCK8 and colony formation assays. The subcutaneous xenograft models revealed that ZFP64 knockdown reduced the volume of formatted tumors, and decreased Ki67 expression in tumors. The opposite effects on cell proliferation and tumorigenesis were demonstrated by ZFP64 overexpression. Furthermore, we suggested that the stem cell-like properties of BC cells were inhibited by ZFP64 depletion, as evidenced by the decreased size and number of formatted mammospheres, the downregulated expressions of OCT4, Nanog, and SOX2 proteins, as well as the reduced proportion of CD44+/CD24− subpopulations. Mechanistically, glycolysis was revealed to mediate the effect of ZFP64 using mRNA-seq analysis. Results showed that ZFP64 knockdown blocked the glycolytic process, as indicated by decreasing glycolytic metabolites, inhibiting glucose consumption, and reducing lactate and ATP production. As a transcription factor, we identified that ZFP64 was directly bound to the promoters of glycolysis-related genes (ALDOC, ENO2, HK2, and SPAG4), and induced the transcription of these genes by ChIP and dual-luciferase reporter assays. Blocking the glycolytic pathway by the inhibition of glycolytic enzymes ENO2/HK2 suppressed the high proliferation and stem cell-like properties of BC cells induced by ZFP64 overexpression. Conclusions These data support that ZFP64 promotes stem cell-like properties and tumorigenesis of BC by activating glycolysis in a transcriptional mechanism.

This paper introduces a novel metaheuristic algorithm, known as the efficient multiplayer battle game optimizer (EMBGO), specifically designed for addressing complex numerical optimization tasks. The motivation behind this research stems from the need to rectify identified shortcomings in the original MBGO, particularly in search operators during the movement phase, as revealed through ablation experiments. EMBGO mitigates these limitations by integrating the movement and battle phases to simplify the original optimization framework and improve search efficiency. Besides, two efficient search operators: differential mutation and Lévy flight are introduced to increase the diversity of the population. To evaluate the performance of EMBGO comprehensively and fairly, numerical experiments are conducted on benchmark functions such as CEC2017, CEC2020, and CEC2022, as well as engineering problems. Twelve well-established MA approaches serve as competitor algorithms for comparison. Furthermore, we apply the proposed EMBGO to the complex adversarial robust neural architecture search (ARNAS) tasks and explore its robustness and scalability. The experimental results and statistical analyses confirm the efficiency and effectiveness of EMBGO across various optimization tasks. As a potential optimization technique, EMBGO holds promise for diverse applications in real-world problems and deep learning scenarios. The source code of EMBGO is made available in https://github.com/RuiZhong961230/EMBGO.

This paper introduces a hierarchical RIME algorithm with multiple search preferences (HRIME-MSP) to tackle complex optimization problems. Although the original RIME algorithm is recognized as an efficient metaheuristic algorithm (MA), its reliance on a single, simplistic search operator poses limitations in maintaining population diversity and avoiding premature convergence. To address these challenges, we propose a hierarchical partition strategy that categorizes the population into superior, borderline, and inferior layers based on their fitness values. Individuals in the superior layer utilize an exploitative local search operator, individuals in the borderline layer inherit the expert-designed soft- and hard-rime search operators from the original RIME algorithm, and individuals in the inferior layer employ the explorative OBL method. We conduct comprehensive numerical experiments on the CEC2017 and CEC2022 benchmarks, six engineering problems, and extreme learning machine (ELM) training tasks to evaluate the performance of HRIME-MSP. Twelve popular and high-performance MA approaches are used as competitor algorithms. The experimental results and statistical analyses confirm the effectiveness and efficiency of HRIME-MSP across various optimization tasks. These findings practically support the scalability and applicability of HRIME-MSP as an advanced optimization technique for diverse real-world applications.

AbstractRadiotherapy (RT) is a highly valuable method in cancer therapy, but its therapeutic efficacy is limited by its side effects and tumour radiation resistance. The resistance is mainly induced by hypoxia in the tumour microenvironment (TME). As a nano-oxygen carrier, Haemoglobin-based oxygen carriers (HBOCs) administration is a promising strategy to alleviate tumour hypoxia which may remodel TME to ameliorate radiation resistance and enable RT more effective. In this study, we administered fractionated RT combined with HBOC to treat Miapaca-2 cell and Hela cell xenografts on nude mice. The study found that HBOC relieved hypoxic environment and down-regulate expression of hypoxia-inducible factor-1α (Hif-1α) both in regular (100 mm3) and large (360/400 mm3) tumours. The proliferation and metastasis of tumour tissue also decreased after HBOC application. Nevertheless, in vivo RT combined with HBOC performed more effectively to suppress tumour growth in large tumours than in regular tumours. This is due to more severe hypoxic regions exist in the large solid tumours compared to the regular counterparts, and HBOC administration may be more effective in alleviating hypoxia in large tumours. Thus, HBOC sensitization therapy is more suitable for large solid tumours.

Abstract Objective We aimed to investigate whether each type of sleep disturbances (i.e., pRBD, EDS, and insomnia) is specifically associated with faster decline in global cognition and different cognitive domains among de novo PD patients. We also assessed the influence of sleep disturbances on core AD CSF biomarkers alterations and conversion to dementia. Methods Prospectively longitudinal data were obtained from the PPMI cohort. Sleep disturbances and cognition ability were assessed by questionnaires at baseline and follow‐up visits. Generalized linear mixed models were utilized to assess the effect of sleep disturbances on cognitive decline and core AD CSF biomarkers change. The associations between sleep disturbances and conversion to dementia were analyzed using Cox regression analysis. Results Baseline pRBD was associated with faster decline in global cognition and all cognitive domains, including verbal episodic memory, visuospatial ability, executive function, language, and processing speed. EDS was associated with faster decline in three cognitive domains, including verbal episodic memory, executive function/working memory, and processing speed. Insomnia was associated with faster decline in global cognition and verbal episodic memory. Meanwhile, pRBD and EDS were associated with longitudinal decrease of CSF Aβ42. Baseline pRBD increased the risk of conversion to dementia. The risk of dementia in PD patients with multiple sleep disturbances also increased compared with those without sleep disturbance. Interpretation Sleep disturbances (i.e., pRBD, EDS, and insomnia) were associated with cognitive decline in early PD. EDS and pRBD were associated with decrease of CSF Aβ42. Moreover, pRBD was associated with conversion to dementia.

Abstract Porphyry-type molybdenum deposits, many of which are in China, supply most of the World’s molybdenum. Of particular importance are the molybdenum deposits located in the Qinling-Dabie region that are responsible for more than half of China’s molybdenum production. A feature that distinguishes this suite of deposits from the better-known Climax and Endako sub-types of porphyry molybdenum deposits is their formation from CO2-rich magmatic-hydrothermal fluids. The role of CO2, if any, in the transport of molybdenum by these fluids, however, is poorly understood. We conducted experiments on the partitioning of molybdenum between H2O-CO2, H2O-NaCl, and H2O-NaCl-CO2 fluids and a felsic melt at 850 °C and 100 and 200 MPa. Here we show that the exsolution of separate (immiscible) brine and vapor leads to the very high brine D Mo values needed for efficient extraction of Mo from the magmas forming Dabie-type porphyry molybdenum deposits.

BackgroundProstate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.MethodsClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.ResultsWe constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.ConclusionBuilding on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.

Abstract Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon‐γ (IFN‐γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine‐2,3‐dioxygenase (IDO)‐ kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan‐to‐phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV‐positive GC continuously secreted IFN‐γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV‐positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV‐positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti‐tumor immunotherapy.

A full-scale hybrid beam consisting of a UHPC slab and FRP truss girder was fabricated. The novel side plate FRP joint characterized with improved load-carrying capacity, stiffness, and preferred failure mode along with the tailored shear connector validated in the previous studies of the authors were adopted. Its flexural performance was characterized and compared with that of hybrid beams employing NC or UHPC slab but I-profile girder. The failure of the proposed hybrid beam subjected to bending was pseudo ductile whereas those of the other two hybrid beams were brittle. The load-carrying capacity and stiffness of the proposed hybrid beam outperformed the other two hybrid beams with comparable dimensions and material properties.

With 252 species, Pseudopoda Jäger, 2000, is the largest genus in the family Sparassidae and is widely distributed in South (49 species in Bhutan, India, Nepal and Pakistan), East (158 species in China and Japan) and Southeast Asia (51 species in Indonesia, Laos, Myanmar, Thailand and Vietnam). Few species have been found in more than one region. In this paper, three new species of Pseudopoda are described from East and Southeast Asia. Among them, one from China: P. fengtongzhaiensis Jäger & Liu, sp. nov. (♀); one from Laos: P. baimai Jäger & Liu, sp. nov. (♀); and one from Thailand: P. inthanonensis Jäger & Liu, sp. nov. (♀). Additionally, the female of P. kavanaughi Zhang, Jäger & Liu, 2023 is described for the first time. Photos of the habitus and genitalia, as well as a distribution map of all four species, are provided.

Carbon fibers (CFs) reinforced alkali-activated (AA) ground granulated blast furnace slag (GGBFS) geopolymer composites have excellent mechanical and thermoelectrical properties, as well as low energy consumption and low CO2 emissions during their production. However, the dispersion of CFs in the geopolymer matrix is always a technical issue in the preparation of the green composite material. Therefore, this study comparatively investigated various dispersion methods, including, mixing sequence (pre-mixing and after-mixing methods), dispersing agent (nano silicon dioxide [nSiO2]), and ultrasonic treatment time (0, 15, 30, and 45 min), as well as CFs content (0.5, 1.0, and 1.5 wt% of GGBFS). The distribution of CFs was then qualitatively and quantitatively evaluated by a series of tests, such as flowability, electrical resistivity, flexural strength, scanning electron microscope (SEM) analysis, and X-ray computed tomography (CT). The experimental results showed that the proposed pre-mixing method provided excellent dispersion characteristics for CFs compared with the after-mixing method. The introduction of nSiO2 can enhance the dispersion of CFs and the mechanical and electrical properties of AA GGBFS geopolymer composites. At a carbon fiber content of 1.5 %, the pre-mixing method and the addition of nSiO2 dispersant reduced the resistivity of the 28-day geopolymer composites by 17.0 % and 38 %, respectively, compared with the after-mixing method. It is feasible to use X-ray CT scanning with the gray-scale frequency map to analyze the dispersion effect of CFs in AA GGBFS geopolymer composites. However, the results were not intuitive when less agglomeration of CFs occurred for the low content of CFs. The scanning method is more applicable to the sample with over 1.0 wt% CFs. The average pixel areas of uniformly dispersed CF bundles in the 2D images of the pre-mixing method and the addition of nSiO2 dispersant specimens were 3.32 % and 6.55 % higher than those of the after-mixing method, respectively. The 2D and 3D scanning results from the dispersion characteristics of CFs were consistent. 2D scanning could provide a time-consuming option for the measurement of CFs dispersion characteristics.

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Most of the energy we need comes from mitochondria. Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. The pathogenesis of DN involves a variety of factors, such as altered haemodynamics, oxidative stress, and inflammation, and studies from animal models suggest that mitochondrial dysfunction plays an important role in the development of DN. Traditional Chinese medicine (TCM) has a history of more than 2,500 years and has rich experience and remarkable efficacy in the treatment of DN. Recent studies have found that TCM may have great potential in regulating mitochondrial dysfunction in the treatment of DN. This review will elucidate the main causes of mitochondrial dysfunction and the relationship with DN, and explore in depth the potential mechanisms of TCM to protect the kidney by improving mitochondrial dysfunction. Current pharmacological treatments for patients with DN do not prevent the inevitable progression to ESRD. With the rich variety of Chinese herbs, TCM is expected to be the most promising candidate for the treatment of DN as we continue to learn more about the mechanisms of DN and incorporate the current advances in extraction techniques.

Using pyrrhotite containing aggregates in concrete foundations can lead to premature deterioration visibly identifiable by extensive map cracking, expansion and deformation of the concrete foundation. The two main expansion mechanisms are: (1) aggregate expansion induced directly by the oxidation of pyrrhotite inclusions and (2) matrix expansion due to the consequent internal sulfate attack (ISA). The relative contribution of these two mechanisms of expansion were investigated in this study. Theoretical calculations based on the practical combinations of oxidation products and degrees of oxidation indicated that aggregate expansion alone may not be sufficient to cause severe deterioration of the concrete incorporating pyrrhotite-bearing aggregate. Observations and this investigation show that this mechanism leads to microcracking which initiates the deterioration process. The combination of microcracking and the release of sulfate facilitates and intensifies the local ISA. The strain derived from the ISA is substantially higher than the typical ultimate tensile strain of a typical matrix used on foundation walls, thus adding additional mechanical stress on the material, and allowing the development of the typical map cracking throughout the concrete.

Vegetation evolution (VEGE) is a newly proposed meta-heuristic algorithm (MA) with excellent exploitation but relatively weak exploration capacity. We thus focus on further balancing the exploitation and the exploration of VEGE well to improve the overall optimization performance. This paper proposes an improved Q-learning based VEGE, and we design an exploitation archive and an exploration archive to provide a variety of search strategies, each archive contains four efficient and easy-implemented search strategies. In addition, online Q-Learning, as well as ε-greedy scheme, are employed as the decision-maker role to learn the knowledge from the past optimization process and determine the search strategy for each individual automatically and intelligently. In numerical experiments, we compare our proposed QVEGE with eight state-of-the-art MAs including the original VEGE on CEC2020 benchmark functions, twelve engineering optimization problems, and wireless sensor networks (WSN) coverage optimization problems. Experimental and statistical results confirm that the proposed QVEGE demonstrates significant enhancements and stands as a strong competitor among existing algorithms. The source code of QVEGE is publicly available at https://github.com/RuiZhong961230/QVEGE.

Abstract Severe sharp angular kyphosis resulting from Pott’s disease typically necessitates surgical intervention. The deployment of three-column osteotomy within the lesion and apical regions has been validated as an effective modality for the amelioration of angular kyphosis. Nonetheless, a propensity for residual kyphosis persists, accompanied by a significant perioperative risk profile. In pursuit of optimizing correctional outcomes and diminishing complication rates, we proposed an innovative surgical approach, utilizing osteotomy in the non-lesioned zones for the rectification of severe angular kyphosis associated with Pott’s disease. This retrospective investigation encompasses 16 subjects who underwent this novel surgical tactic, involving osteotomies in non-lesioned vertebral segments, at our institution from 2016 to 2018. Radiographic measures, encompassing kyphotic angle and sagittal vertical axis (SVA), were documented at baseline and during terminal follow-up. Neurological status was evaluated via the American Spinal Injury Association (ASIA) grading system. Operative duration, volume of hemorrhage, and perioperative complications were systematically recorded. The cohort included 6 males and 10 females with an average age of 30.7 ± 11.41 years. Follow-up intervals spanned 24 to 42 months. Mean operative time and blood loss were 492 ± 127.3 min and 1791 ± 788.8 ml, respectively. The kyphotic angle improved from 97.6 ± 14.6° to 28.8 ± 18.70°. In cases with lumbar afflictions, vertebral restoration was achieved (L1–L5 and L2–S1). Initial mean SVA of 6.7 ± 3.58 cm was reduced to 3.3 ± 1.57 cm at follow-up. Neurological function enhancement was observed in six patients, while ten maintained baseline status. Complication rates, including wound infection and rod fracture at 12 months, were observed in approximately 11.8% of cases. Our findings suggest that the surgical strategy is both effective and safe for addressing severe angular kyphosis due to Pott’s disease, contingent upon the expertise of the surgical unit.

This scholarly paper presents an innovative conceptual framework that draws upon insights from fictional narratives to inform the evolution of the metaverse, a burgeoning digital ecosystem with transformative potential. The study examines key elements of fictional works, including world-building techniques, social interaction dynamics, narrative structures, and ethical considerations, to illuminate the complexities of designing immersive virtual environments. Our primary findings indicate that consistency and coherence in world-building significantly enhance user immersion and engagement in virtual environments. Furthermore, the integration of diverse cultural and historical elements in the metaverse can foster inclusivity and enrich user experiences. Additionally, ethical considerations, such as privacy, digital identity, and accessibility, are paramount to the development of a responsible and inclusive metaverse. These findings underscore the importance of fiction as a source of inspiration, foresight, and caution for metaverse development. The proposed framework aims to amalgamate the imaginative realms of fiction with the practical applications of virtual environments, thereby facilitating the creation of a metaverse that is engaging, inclusive, and ethically responsible.

BackgroundIn observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two.MethodsGenetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran’s Q test, and Leave-one-out test) were used to test the robustness of the results.ResultsAfter Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent.ConclusionThe results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.

Objective: Chondrocyte death is the hallmark of cartilage degeneration during osteoarthritis (OA). However, the specific pathogenesis of cell death in OA chondrocytes has not been elucidated. This study aims to validate the role of CDKN1A, a key programmed cell death (PCD)-related gene, in chondrogenic differentiation using a combination of single-cell and bulk sequencing approaches. Design: OA-related RNA-seq data (GSE114007, GSE55235, GSE152805) were downloaded from Gene Expression Omnibus database. PCD-related genes were obtained from GeneCards database. RNA-seq was performed to annotate the cell types in OA and control samples. Differentially expressed genes (DEGs) among those cell types (scRNA-DEGs) were screened. A nomogram of OA was constructed based on the featured genes, and potential drugs targeting the featured genes were predicted. The presence of key genes was confirmed using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC). Micromass culture and Alcian blue staining were used to determine the effect of CDKN1A on chondrogenesis. Results: Six cell types, namely HomC, HTC, RepC, preFC, FC, and RegC, were annotated in scRNA-seq data. Five featured genes (JUN, CDKN1A, HMGB2, DDIT3, and DDIT4) were screened by multiple biological information analysis methods. TAXOTERE had the highest ability to dock with DDIT3. Functional analysis indicated that CDKN1A was enriched in processes related to collagen catabolism and acts as a positive regulator of autophagy. Additionally, CDKN1A was found to be associated with several KEGG pathways, including those involved in acute myeloid leukemia and autoimmune thyroid disease. CDKN1A was confirmed down-regulated in the joint tissues of OA mouse model and OA model cell. Inhibiting the expression of CDKN1A can significantly suppress the differentiation of OA chondrocytes. Conclusion: Our findings highlight the critical role of CDKN1A in promoting cartilage formation in both in vivo and in vitro and suggest its potential as a therapeutic target for OA treatment.

Introduction Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers’ characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC miniprogram. Methods Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC miniprogram (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. Results The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0–60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). Conclusions Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.

Abstract This paper proposes a novel algorithm named surrogate ensemble assisted differential evolution with efficient dual differential grouping (SEADECC-EDDG) to deal with large-scale expensive optimization problems (LSEOPs) based on the CC framework. In the decomposition phase, our proposed EDDG inherits the framework of efficient recursive differential grouping (ERDG) and embeds the multiplicative interaction identification technique of Dual DG (DDG), which can detect the additive and multiplicative interactions simultaneously without extra fitness evaluation consumption. Inspired by RDG2 and RDG3, we design the adaptive determination threshold and further decompose relatively large-scale sub-components to alleviate the curse of dimensionality. In the optimization phase, the SEADE is adopted as the basic optimizer, where the global and the local surrogate model are constructed by generalized regression neural network (GRNN) with all historical samples and Gaussian process regression (GPR) with recent samples. Expected improvement (EI) infill sampling criterion cooperated with random search is employed to search elite solutions in the surrogate model. To evaluate the performance of our proposal, we implement comprehensive experiments on CEC2013 benchmark functions compared with state-of-the-art decomposition techniques. Experimental and statistical results show that our proposed EDDG is competitive with these advanced decomposition techniques, and the introduction of SEADE can accelerate the convergence of optimization significantly.

Abstract This paper proposes a novel surrogate ensemble-assisted hyper-heuristic algorithm (SEA-HHA) to solve expensive optimization problems (EOPs). A representative HHA consists of two parts: the low-level and the high-level components. In the low-level component, we regard the surrogate-assisted technique as a type of search strategy and design the four search strategy archives: exploration strategy archive, exploitation strategy archive, surrogate-assisted estimation archive, and mutation strategy archive as low-level heuristics (LLHs), each archive contains one or more search strategies. Once the surrogate-assisted estimation archive is activated to generate the offspring individual, SEA-HHA first selects the dataset for model construction from three principles: All Data, Recent Data, and Neighbor, which correspond to the global and the local surrogate model, respectively. Then, the dataset is randomly divided into training and validation data, and the most accurate model built by polynomial regression (PR), support vector regression (SVR), and Gaussian process regression (GPR) cooperates with the infill sampling criterion is employed for solution estimation. In the high-level component, we design a random selection function based on the pre-defined probabilities to manipulate a set of LLHs. In numerical experiments, we compare SEA-HHA with six optimization techniques on 5-D, 10-D, and 30-D CEC2013 benchmark functions and three engineering optimization problems with only 1000 fitness evaluation times (FEs). The experimental and statistical results show that our proposed SEA-HHA has broad prospects for dealing with EOPs.

Abstract Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body’s oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Abstract Background and aim The literature is sparse on the association between serum liver fibrosis markers and the development of hepatic decompensation in patients with compensated cirrhosis. We aimed to assessed whether the serum liver fibrosis markers are predictive of the occurrence of hepatic decompensation. Methods We ascertained 688 cirrhotic patients with varying etiologies, between December 2015 to December 2019. Serum hyaluronic acid (HA), laminin (LN), collagen IV (CIV), and N-terminal propeptide of type III collagen (PIIINP) levels were measured at enrollment. All subjects were followed for at least 6 months for occurrence of hepatic decompensation. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of hepatic decompensation during follow-up. Results During a median follow-up of 22.0 (13.0–32.0) months, decompensation occurred in 69 (10.0%) patients. Multivariate analysis indicated that higher LN (HR: 1.008, 95% confidence interval [CI]: 1.002–1.014, P = 0.011) and CIV (HR: 1.004, 95% CI: 1.001–1.007, P = 0.003) levels were independently associated with hepatic decompensation. Furthermore, patients in the tertile 2 and tertile 3 groups for CIV levels had HRs of 4.787 (1.419, 16.152) (P = 0.012) and 5.153 (1.508, 17.604) (P = 0.009), respectively, for occurrence of decompensation event compared with those in the tertile 1 group. Conclusion Serum liver fibrosis markers, particularly in CIV, appeared to be reliable biomarkers of disease progression and liver decompensation in patients with compensated cirrhosis with varying etiologies.

Abstract Background The severe rigid scoliosis patients with type I respiratory failure could not tolerate complicated corrective surgery. Preoperative halo-pelvic distraction (HPD) is used to reduce the curve magnitude and improve the pulmonary function before surgery. The present study aimed to retrospectively analyze the pulmonary and clinical outcomes of preoperative HPD in severe rigid spinal deformity with type I respiratory failure. Methods Eighteen cases of severe rigid scoliosis and type I respiratory failure treated with preoperative HPD and corrective surgery for spinal deformity between 2016 and 2018 were retrospectively reviewed. Patient demographics, major coronal curve and kyphosis, correction rates, heights, pulmonary function, distraction time, and postoperative neurological complications were recorded for all cases. Results The averaged duration of distraction was 9.1 ± 2.3 months. The coronal curve was corrected from 168° ± 14° to 58° ± 11° at the end of HPD. The kyphosis curve reduced from 151° ± 29° to 65° ± 10°. Meanwhile, the mean stand body height increased by 23.9 ± 5.3 cm. Significantly increased mean FVC (1.52 ± 0.43 L vs. 0.95 ± 0.44 L) and improved percent-predicted values for FVC (37 ± 10% vs. 23 ± 9%) were observed after HPD. The pressure of oxygen (PaO2) increased from 54.5 ± 2.0 to 84.8 ± 4.7 mmHg. Scoliosis and kyphosis curve, respectively, averaged 48 ± 8°and 30 ± 14° after final fusion and instrumentation, with a mean correction of 71% and 80%, respectively. No severe complication occurred during the distraction. Conclusions HPD may be useful for severe rigid scoliosis patients with type I respiratory failure. Pulmonary functions in patients with severe rigid scoliosis can be significantly improved by HPD. They are then better able to tolerate complicated corrective surgery.

Abstract Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

Abstract Background Patients with severe kyphotic deformity (Cobb > 100°) secondary to ankylosing spondylitis (AS) occasionally cannot undergo corrective surgery in the prone position. Osteotomy in the lateral position might provide a possible solution. In this study, we aim to evaluate the clinical efficacy and safety of staged osteotomy in the lateral position for the treatment of AS-related severe kyphosis with a minimum of 2-year follow-up. Methods In total, 23 patients who underwent staged osteotomy in the lateral position from October 2015 to June 2017 were analyzed. In the first stage of surgery, all but one patient underwent a single-level Ponte osteotomy, which was followed by a pedicle subtraction osteotomy in the second stage. Mean follow-up was 30.8 ± 4.6 months. Global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), osteotomized vertebra intervertebral angle (OVI), chin-brow vertical angle (CBVA), Oswestry Disability Index (ODI) score and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) were all compared pre- and postoperation. Results All kyphosis parameters were significantly improved (all P

BackgroundObservational studies have shown that changes in circulating cytokine/growth factor levels occur throughout the initiation and progression of ankylosing spondylitis (AS), yet whether they are etiologic or downstream effects remains unclear. In this study, we performed a summarized-level bidirectional Mendelian randomization (MR) analysis to shed light on the causal relationship between the two.MethodsGenetic instrumental-variables (IVs) associated with circulating cytokine/growth factor levels were derived from a genome-wide association study (GWAS) of 8,293 European individuals, whereas summary data for the AS were obtained from a FinnGen GWAS of 166,144 participants. We used the inverse-variance-weighted (IVW) method as the main analysis for causal inference. Furthermore, several sensitivity analyses (MR-Egger, weighted median, MR-PRESSO and Cochran’s Q test) were utilized to examine the robustness of the results. Finally, reverse MR analysis was performed to assess reverse causality between AS and circulating cytokine/growth factor levels.ResultsAfter Bonferroni correction, circulating levels of Cutaneous T-cell attracting (CTACK) and Monocyte specific chemokine 3 (MCP-3) were positively associated with a higher risk of AS (odds ratio [OR]: 1.224, 95% confidence interval [95% Cl]: 1.022 ~ 1.468, P = 0.028; OR: 1.250, 95% Cl: 1.016 ~ 1.539, P = 0.035). In addition, elevated circulating levels of Basic fibroblast growth factor (FGF-basic), Granulocyte colony-stimulating factor (G-CSF) and MCP-3 was considered a consequence of AS disease (β = 0.023, P = 0.017; β = 0.017, P = 0.025; β = 0.053, P = 0.025). The results of the sensitivity analysis were generally consistent.ConclusionThe present study supplies genetic evidence for the relationship between circulating cytokine levels and AS. Targeted interventions of specific cytokines may help to reduce the risk of AS initiation and progression.

Introduction Many smokers in China desire to quit, though the success rate among adults is low. This study evaluated the effects of QuitAction, a WeChat smoking cessation platform, summarized the intervention experience of the smoking cessation platform, identified aspects of the platform that necessitated improvement, and provided references for further optimization of the smoking cessation platform. Methods This single-arm study was conducted in Hunan, China, from September 2020 to October 2021. Regular smokers, who were aged ≥15 years and willing to quit smoking using QuitAction, were recruited. An in-application questionnaire evaluated participants’ baseline smoking status and intention to quit smoking. The QuitAction program included questionnaires regarding the participants’ ongoing smoking cessation status at 24 hours, one week, one month and three months after quitting. The smoking cessation procedure was discontinued if the participant had no intention of continuing. The smoking cessation rate, influencing success factors, frequency of use satisfaction, and helpfulness of QuitAction were recorded. Results A total of 303 participants registered and logged into the QuitAction program, including 59 with incomplete information and 64 with no intention of quitting. The study finally included 180 participants. The smoking cessation rate was 33.9% at 24 hours, 27.2% at one week, 26.1% at one month, and 25.0% at three months. QuitAction was reported as helpful by 94.9% of participants and 95.7% were satisfied with the program. Participants with a quitting difficulty score of 80–100 were less likely to quit smoking than participants with a difficulty score of 0–60 (OR=0.28; 95% CI: 0.10–0.78; p=0.015). Participants using the platform ≥5 times were more likely to quit smoking than those who used the platform

Abstract Background It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD+) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate‐limiting enzyme in NAD+ biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction. Methods To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow‐twitch (type I) or fast‐twitch (type II) fibres, rabbit models of rotator cuff tear‐induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection‐induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross‐sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy. Results Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86 ± 0.25 to 5.10 ± 0.79 g; P

Summary: Immunosuppressive myeloid cell populations have been documented in small cell lung cancer (SCLC) subtypes, playing a key role in remolding the tumor microenvironment (TME). However, the cancer-associated transcriptional features of monocytes and tumor-associated macrophages (TAMs) in SCLC remain poorly understood. Herein, we analyzed the molecular features and functions of monocyte/macrophage subsets aiming to inhibit monocyte recruitment and pro-tumor behavior of macrophages. We observe that NEUROD1-high SCLC subtype (SCLC-N) exhibits subtype-specific hypersialylation induced by the unique target c-Myc (MYC) of NEUROD1. The hypersialylation can alter macrophage phenotypes and pro-tumor behavior by regulating the expression of the immune-inhibiting lectin receptors on monocyte-derived macrophages (MDMs) in SCLC-N. Inhibiting the aberrant sialic acid metabolic pathways in SCLC can significantly enhance the phagocytosis of macrophages. This study provides a comprehensive overview of the cancer-specific immune signature of monocytes and macrophages and reveals tumor-associated biomarkers as potential therapeutic targets for SCLC.

Abstract Objective In the context of aging, Chinese families consisting of more than three generations (grandparents, parents, children) are the norm. The second generation (parents) and other family members may establish a downward (contact only with children) or two-way multi-generational relationship (contact with children and grandparents). These multi-generational relationships may have the potential effect on multimorbidity burden and healthy life expectancy in the second generation, but less is known about the direction and intensity of this effect. This study aims to explore this potential effect. Methods We obtained longitudinal data from the China Health and Retirement Longitudinal Study from 2011 to 2018, which included 6,768 people. Cox proportional hazards regression was used to assess the association between multi-generational relationships and the number of multimorbidity. The Markov multi-state transition model was used to analyze the relationship between multi-generational relationships and the severity of multimorbidity. The multistate life table was used to calculate healthy life expectancy for different multi-generational relationships. Results The risk of multimorbidity in two-way multi-generational relationship was 0.830 (95% CIs: 0.715, 0.963) times higher than that in downward multi-generational relationship. For mild multimorbidity burden, downward and two-way multi-generational relationship may prevent aggravation of burden. For severe multimorbidity burden, two-way multi-generational relationship may aggravate the burden. Compared with two-way multi-generational relationship, the second generations with downward multi-generational relationship has a higher healthy life expectancy at all ages. Conclusion In Chinese families with more than three generations, the second generations with severe multimorbidity burden may aggravate the condition by providing support to elderly grandparents, and the support provided by offspring to the second generations plays a vital positive role in improving the quality of life and narrowing the gap between healthy life expectancy and life expectancy.

Abstract Many optimization problems suffer from noise, and the noise combined with the large-scale attributes makes the problem complexity explode. Cooperative coevolution (CC) based on divide and conquer decomposes the problems and solves the sub-problems alternately, which is a popular framework for solving large-scale optimization problems (LSOPs). Many studies show that the CC framework is sensitive to decomposition, and the high-accuracy decomposition methods such as differential grouping (DG), DG2, and recursive DG (RDG) are extremely sensitive to sampling accuracy, which will fail to detect the interactions in noisy environments. Therefore, solving LSOPs in noisy environments based on the CC framework faces unprecedented challenges. In this paper, we propose a novel decomposition method named linkage measurement minimization (LMM). We regard the decomposition problem as a combinatorial optimization problem and design the linkage measurement function (LMF) based on Linkage Identification by non-linearity check for real-coded GA (LINC-R). A detailed theoretical analysis explains why our proposal can determine the interactions in noisy environments. In the optimization, we introduce an advanced optimizer named modified differential evolution with distance-based selection (MDE-DS), and the various mutation strategy and distance-based selection endow MDE-DS with strong anti-noise ability. Numerical experiments show that our proposal is competitive with the state-of-the-art decomposition methods in noisy environments, and the introduction of MDE-DS can accelerate the optimization in noisy environments significantly.

The deep learning-based coding schemes for lenslet images combine coding standards and view synthesis through Deep Learning (DL) models, where the compression efficiency is heavily influenced by the coding structure and quality of synthesized views. To exploit the inter-view redundancy among Sub-Aperture Images (SAIs), this paper proposes a hybrid closed-loop coding system that uses a novel coding structure based on checkerboard interleaving at a frame level. The frame-wise checkerboard interleaving method partitions an Original SAIs’ Set (OSS) of images into two mutually exclusive subsets, each consisting of alternating rows and columns of SAIs. We utilize the video coding standard Versatile Video Coding (VVC) to encode one subset while proposing a novel rate constraint-reinforced 3D Convolutional Neural Networks (CNNs) to predict the other subset, referred to as the complement subset. The rate constraint-reinforced 3D CNNs is newly designed with a gradient loss and reinforced rate cost to improve synthesized SAIs’ image quality and bit cost saving simultaneously. Experimental results on the light field image dataset demonstrate that the proposed hybrid coding system outperforms both HEVC_LDP and the previous state-of-the-art (SOTA), achieving an average BD-Bitrate savings of 41.58% and 23.31%, respectively.