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Abstract Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for “cancer of unknown primary”, where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.

Abstract Tuning the properties of a pair of entangled electron and hole in a light-induced exciton is a fundamentally intriguing inquiry for quantum science. Here, using semiconducting hybrid perovskite as an exploratory platform, we discover that Nd2+-doped CH3NH3PbI3 (MAPbI3) perovskite exhibits a Kondo-like exciton-spin interaction under cryogenic and photoexcitation conditions. The feedback to such interaction between excitons in perovskite and the localized spins in Nd2+ is observed as notably prolonged carrier lifetimes measured by time-resolved photoluminescence, ~10 times to that of pristine MAPbI3 without Nd2+ dopant. From a mechanistic standpoint, such extended charge separation states are the consequence of the trap state enabled by the antiferromagnetic exchange interaction between the light-induced exciton and the localized 4 f spins of the Nd2+ in the proximity. Importantly, this Kondo-like exciton-spin interaction can be modulated by either increasing Nd2+ doping concentration that enhances the coupling between the exciton and Nd2+ 4 f spins as evidenced by elongated carrier lifetime, or by using an external magnetic field that can nullify the spin-dependent exchange interaction therein due to the unified orientations of Nd2+ spin angular momentum, thereby leading to exciton recombination at the dynamics comparable to pristine MAPbI3.

Abstract Background Patient safety is paramount for all healthcare agencies. Health professionals' lack of patient safety competencies threaten patients’ lives, and increase patients, families, hospitals, and social burdens. The new nurse-related patient safety issues have particularly attracted much attention. The aim of this study was to examine the impacts of practice environment and job stress on new nurses' patient safety attitudes by employing the job demands–resources model. Methods The study used a cross-sectional structural equation modeling (SEM). A convenience sample of 370 new nurses was recruited from seven tertiary hospitals in Anhui province, China, from April 2022 to August 2022. Data were collected using self-report questionnaires including the Chinese version of the Nurse Job Stressors Scale, the Practice Environment Scale, and the Safety Attitudes Questionnaire. Results New nurses' patient safety attitudes scores were moderate (126.99 ± 14.39). Practice environment had a significant direct effect on job stress (β = -0.337, t = 6.120), patient safety attitudes (β = 0.604, t = 13.766), practice environment had an indirect effect on patient safety attitudes through job stress (β = 0.066, t = 3.690), and the indirect effect accounted for 9.9% of the total effect. This model was able to explain 48.3% of patient safety attitudes with moderate prediction accuracy. Conclusions This study emphasizes the importance of improving new nurses' attitudes toward patient safety. Hospital administrators should develop policies and strategies to address job characteristics, and establish a favorable work environment to reduce new nurses' job stress as well as to improve patient safety.

Machine learning combined with traditional experimental methods can promote the efficient research and development of materials. In this work, five kinds of algorithm models combined with a genetic algorithm (GA) were used to optimize the compositions of the alloyed high manganese steel. And then the effect of solid solution temperatures on the microstructure, mechanical properties, and impact wear properties of the steel were systematically investigated. The results showed that Categorical Boosting (CB) model exhibited the high validation accuracy (R2 > 0.95, RMSE

Abstract Objective Incontinence seriously affects the lives of middle‐aged and older people. Pelvic floor muscle assessment is very important for incontinence, and handgrip strength can be used as an auxiliary diagnostic tool. Our study aims to find new cutoff points of handgrip strength as early indicators of incontinence and analyze the association between low handgrip strength and incontinence among Chinese middle‐aged and older people. Methods Participants were recruited from the 2015 China Health and Retirement Longevity Study. Receiver operating characteristic (ROC) curves were used to find the handgrip strength cutoff point. Logistic regression analysis was performed to explore other incontinence‐related risk factors. Results The study included 10,229 middle‐aged and older people. Compared with normal handgrip strength participants, medium strength participants had 1.510 [men, 95% confidence interval (CI) = 1.017–2.243] and 1.792 (women, 95% CI = 1.294–2.480) times greater risk of incontinence, and low strength participants had 2.420 (men, 95% CI = 1.787–3.277) and 1.516 (women, 95% CI = 1.130–2.032) times greater risk of incontinence. Trend test results showed that the risk of incontinence increased with decreasing handgrip strength in middle‐aged and older people. Conclusions Our study suggests that handgrip strength

Abstract Octacosanol is a plant natural product with the potential to ameliorate alcoholic liver injury. However, its poor solubility limits its application in the food industry. This study first verified that octacosanol has a favorable effect on acute and subchronic alcoholic liver injury in mice by protecting the gastric mucosa and ameliorating disease levels. Additionally, octacosanol microcapsules were prepared under the optimal drying conditions of the feed flow rate of 400 mL/h and drying temperature of 180°C to improve the ameliorative effects of octacosanol, with moisture content, water activity, dispersibility, and solubility of 1.53%, 0.16%, 89.84%, and 95.30%, respectively. The microcapsules had a spherical structure, and the droplet sizes after redissolution ranged from 0.061 to 4.63 µm. Instrumental measurements and simulated digestion experiments have shown that microencapsulation enhanced the solubility and thermal stability of octacosanol, with 90.88% of the octacosanol being continuously released. As expected, microencapsulation significantly enhanced the effect of octacosanol in ameliorating alcoholic liver injury by determining the disease index in the mice model. This study demonstrated the beneficial effects of octacosanol on alcoholic liver injury and explored a viable method to improve its solubility and bioaccessibility, thereby enhancing its therapeutic efficacy for the treatment of alcoholic liver injury.

Abstract Background Monoterpenes are among the most important volatile aromatic compounds contributing to the flavor and aroma of grapes and wine. However, the molecular basis of monoterpene biosynthesis has not yet been fully elucidated. Results In our study, transcriptomics and gas chromatography-mass spectrometry (GC-MS) were used to mine candidate genes and transcription factors involved in monoterpene biosynthesis between high-monoterpene and zero-monoterpene table grape cultivars. We found that monoterpene biosynthesis was positively correlated by the expression of five genes encoding 1-deoxy-D-xylulose-5-phosphate synthase (VvDXSs), one encoding 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (VvHDR), three hydroxy-3-methylglutaryl-CoA synthases (VvHMGSs) and one mevalonate kinase (VvMVK), whereas the expression of one isopentenyl diphosphate isomerase (VvIDI) and one 3-hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) negatively correlated monoterpene biosynthesis. Of these genes, VvIDI was selected to validate its function in monoterpene accumulation through a transient overexpression experiment, and was shown to inhibit the biosynthesis of grape linalool and α-terpineol. Meanwhile, we found that a 64-amino acid extension sequence at the N-terminus can guide the VvIDI protein to target the chloroplast. Conclusions The findings of this study should help to guide future functional analysis of key genes as well as mining the potential regulatory mechanism of monoterpene biosynthesis in grapes and grape products.

Offshore wind farms are becoming increasingly distant from onshore centralized control centers, and the communication delays between them inevitably introduce time delays in the measurement signal of the primary frequency control. This causes a deterioration in the performance of the primary frequency control and, in some cases, may even result in frequency instability within the power system. Therefore, a frequency response model that incorporates communication delays was established for power systems that integrate offshore wind power. The Padé approximation was used to model the time delays, and a linearized frequency response model of the power system was derived to investigate the frequency stability under different time delays. The influences of the wind power proportion and frequency control parameters on the system frequency stability were explored. In addition, a Smith delay compensation control strategy was devised to mitigate the effects of communication delays on the system frequency dynamics. Finally, a power system incorporating offshore wind power was constructed using the MATLAB/Simulink platform. The simulation results demonstrate the effectiveness and robustness of the proposed delay compensation control strategy.

Abstract The spatiotemporal regulation of inflammasome activation remains unclear. To examine the mechanism underlying the assembly and regulation of the inflammasome response, here we perform an immunoprecipitation-mass spectrometry analysis of apoptosis-associated speck-like protein containing a CARD (ASC) and identify NCF4/1/2 as ASC-binding proteins. Reduced NCF4 expression is associated with colorectal cancer development and decreased five-year survival rate in patients with colorectal cancer. NCF4 cooperates with NCF1 and NCF2 to promote NLRP3 and AIM2 inflammasome activation. Mechanistically, NCF4 phosphorylation and puncta distribution switches from the NADPH complex to the perinuclear region, mediating ASC oligomerization, speck formation and inflammasome activation. NCF4 functions as a sensor of ROS levels, to establish a balance between ROS production and inflammasome activation. NCF4 deficiency causes severe colorectal cancer in mice, increases transit-amplifying and precancerous cells, reduces the frequency and activation of CD8+ T and NK cells, and impairs the inflammasome-IL-18-IFN-γ axis during the early phase of colorectal tumorigenesis. Our study implicates NCF4 in determining the spatial positioning of inflammasome assembly and contributing to inflammasome-mediated anti-tumor responses.

Abstract. Background:. Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Methods:. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results:. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. Conclusions:. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Abstract To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: “urinal collecting apparatus dominated pattern” (40.3%), “bladder compression dominated pattern” (30.7%), “intermittent catheterization dominated pattern” (19.3%) and “urethral indwelling catheterization dominated pattern” (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

Abstract Background Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. Methods Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni–NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. Results In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αβ T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. Conclusion Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Abstract The engineered clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas) system is currently widely applied in genetic editing and transcriptional regulation. The catalytically inactivated CasRx (dCasRx) has the ability to selectively focus on the mRNA coding region without disrupting transcription and translation, opening up new avenues for research on RNA modification and protein translation control. This research utilized dCasRx to create a translation-enhancement system for mammals called dCasRx-eIF4GI, which combined eukaryotic translation initiation factor 4G (eIF4GI) to boost translation levels of the target gene by recruiting ribosomes, without affecting mRNA levels, ultimately increasing translation levels of different endogenous proteins. Due to the small size of dCasRx, the dCasRx-eIF4GI translation enhancement system was integrated into a single viral vector, thus optimizing the delivery and transfection efficiency in subsequent applications. Previous studies reported that ferroptosis, mediated by calcium oxalate (CaOx) crystals, significantly promotes stone formation. In order to further validate its developmental potential, it was applied to a kidney stone model in vitro and in vivo. The manipulation of the ferroptosis regulatory gene FTH1 through single-guide RNA (sgRNA) resulted in a notable increase in FTH1 protein levels without affecting its mRNA levels. This ultimately prevented intracellular ferroptosis and protected against cell damage and renal impairment caused by CaOx crystals. Taken together, this study preliminarily validated the effectiveness and application prospects of the dCasRx-eIF4GI translation enhancement system in mammalian cell-based disease models, providing novel insights and a universal tool platform for protein translation research and future therapeutic approaches for nephrolithiasis.

Abstract The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Discriminating strong aroma-type Baijiu (SAB) of different origins was significant for product quality control and origin protection. In this study, a 4×3 sensor array was constructed based on the Ag nanoprism (AgNPR) etching mechanism, in which four AgNPRs varying in shape and size were used as sensing materials, and two metal ions and one oxide anion were used as oxidation etchants. With this array, colorimetric reaction was conducted on 41 representative SAB samples from Sichuan, Jianghuai and North China. The obtained colorimetric signal values were subjected to linear discriminant analysis (LDA). Furthermore, some samples of unknown origin were selected to perform external validation on the discrimination model. Based on the results of colorimetric reaction mechanism, the samples could promote the etching effect of AgNPRs, which might be related to various organic acids contained in Baijiu. Sample discrimination showed that single array produced a comparatively low effect on samples of different origins. The combination of three arrays significantly improved the discrimination effect, whose rate of origin discrimination was up to 99% for 41 samples, and was up to 98% for 15 unknown samples. With combined array, the discriminant rates of 21 samples from 5 brands in Sichuan and 13 samples from 3 brands in Jianghuai could reach 99% and 100%, respectively, while all the discriminant rates could reach 100% for different grades of products from various manufacturers in Sichuan with single array. Being simple and fast, the nanocolorimetric sensing method adopted in this study is not only applicable to product identification and anti-counterfeiting, but also be auxiliarily used for quality control in production process, laying a research foundation for intelligent quality monitoring of Baijiu.

Parameters of foam penetration in earth pressure balance (EPB) shield tunnelling, such as permeability coefficients and penetration distances, significantly impact tunnel face stability. However, existing studies have faced inaccuracies in analysing these parameters due to imitations in experimental methods. This study addresses this issue by employing enhanced methods for a more precise analysis of foam penetration. Experiments involving three distinct sand types (coarse, medium, and fine) and three foam expansion ratios (FER) (10, 15, and 20) are conducted using a modified model test setup. Benefiting from a novel computer vision-based method, the model test outcomes unveil two distinct foam penetration paths: liquid migration (Lw) and bubble migration (Lf). Three penetration phases — namely, injection, blockage & drainage, and breakage — are identified based on Lw and Lf variations. The initial “injection” phase conforms to Darcy's law and is amenable to mathematical description. The foam with FER of 15 has the maximum viscosity and, hence the Lf and permeability in the penetration tests with FER of 15 are the lowest in the same sand. The bubble size distribution of foam with different FER shows minor differences. Nevertheless, the characteristics of foam penetration vary due to the distinct particle size distribution (PSD) of different sands. Foam penetration creates low-permeability layers in both medium and fine sands due to the larger bubble size of the foam compared to the estimated pore sizes of medium and fine sands. While the coarse sand results in a different situation due to its large pore size. The distinctive characteristics of foam penetration in different sand strata are notably shaped by FER, PSD, and pore size distributions. These insights shed light on the complex interactions during foam penetration at the tunnel face, contributing valuable knowledge to EPB shield tunnelling practices.

Abstract Cellular behavior is regulated by mechanical signals within the cellular microenvironment. Additionally, changes of temperature, blood flow, and muscle contraction also affect cellular state and the development of diseases. In clinical practice, physical therapy techniques such as ultrasound, vibration, exercise, cold therapy, and hyperthermia are commonly employed to alleviate pain and treat diseases. However, the molecular mechanism about how these physiotherapy methods stimulate local tissues and control gene expression remains unknow. Fortunately, the discovery of YAP filled this gap, which has been reported has the ability to sense and convert a wide variety of mechanical signals into cell-specific programs for transcription, thereby offering a fresh perspective on the mechanisms by which physiotherapy treat different diseases. This review examines the involvement of Hippo/YAP signaling pathway in various diseases and its role in different physical therapy approaches on diseases. Furthermore, we explore the potential therapeutic implications of the Hippo/YAP signaling pathway and address the limitations and controversies surrounding its application in physiotherapy.

Abstract Background The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. Methods We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). Results The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. Conclusion These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Abstract Post-stroke depression (PSD) is regarded as the consequence of multiple contributors involving the process of cognition, mood and autonomic system, with the specific mechanism unclear yet. As a common type of stroke-heart syndromes, post-stroke arrhythmia shared some common pathogenesis with PSD. We presumed that post-stroke arrhythmia might be an early distinguishable marker for the presence of PSD and aimed to verity their association in this study. Patients with first-ever ischemic stroke were enrolled. The presence of post-stroke ectopic arrhythmia and the symptoms of arrhythmia were recorded with anti-arrhythmia drugs prescribed when necessary. Patients were followed up 3 months later to identify their presence and severity of PSD using Hamilton Depression Scale (HAMD) and also presence and severity of arrhythmia. Characteristics including the prevalence of various types of arrhythmias were compared between PSD and non-PSD groups. The HAMD scores were compared between patients with and without arrhythmia in PSD group. Logistic regression was used to identify the independent predictor of PSD. Patients with PSD had higher prevalence of post-stroke arrhythmia especially newly-detected arrhythmia, symptomatic arrhythmia and poor-controlled arrhythmia. In PSD group, patients of post-stroke arrhythmia had higher scores of HAMD than those without arrhythmia. Presence of newly-detected, symptomatic and poor-controlled arrhythmias were independent predictor of PSD. post-stroke arrhythmia especially newly-detected arrhythmia and symptomatic arrhythmia could be an early predictor of PSD. Successful control of arrhythmia was associated with reduced prevalence and severity of PSD.

Abstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. Methods In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP–RIPK1–NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model. Results In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. Conclusions These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.

Abstract Background The objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD). Methods All participants’ fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples’Hospital. The levels of three urinary pesticides were measured using β-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver. Results 53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD. Conclusion The present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.

Abstract Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables’ pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p

The bench slope within an open-pit coal mine plays an important supporting role for coal resource production and transportation. The stability evaluation of the slope is of great significance in guiding continuous mining operations within the mine. This study leverages monitoring data and geological surveys of the slope, employing the analytic hierarchy process (AHP) to assign weights to slope stability analysis factors. Additionally, it employs the principle of maximum membership degree, taking into account various parameters such as slope geometry, geological data, meteorological and hydrological information, and field monitoring data. This paper establishes an analytic hierarchy process - fuzzy comprehensive evaluation model for slope stability assessment. Subsequently, the model is applied to analyze the stability of the north slope at the Zhahanao’er open-pit coal mine. The research indicates that, accordingly to the established slope analytic hierarchy process - fuzzy comprehensive evaluation model, the northern slope is deemed to be fundamentally stable. The numerical simulated FOS (factor of safety) of 1.121 aligns remarkably well with model results. It is comprehensive and accurate since the model can fully consider the contribution of multiple information to the stability of slope.

Abstract Background Nowadays, both lateral mass screw (LMS) and pedicle screw were effective instrumentation for posterior stabilization of cervical spine. This study aims to evaluate the feasibility of a new free-hand technique of C7 pedicle screw insertion without fluoroscopic guidance for cervical spondylotic myelopathy (CSM) patients with C3 to C6 instrumented by lateral mass screws. Methods A total of 53 CSM patients underwent lateral mass screws instrumentation at C3 to C6 levels and pedicle screw instrumentation at C7 level were included. The preoperative 3-dimenional computed tomography (CT) reconstruction images of cervical spine were used to determine 2 different C7 pedicle screw trajectories. Trajectory A passed through the axis of the C7 pedicle while trajectory B selected the midpoint of the base of C7 superior facet as the entry point. All these 53 patients had the C7 pedicle screw inserted through trajectory B by free-hand without fluoroscopic guidance and the postoperative CT images were obtained to evaluate the accuracy of C7 pedicle screw insertion. Results Trajectory B had smaller transverse angle, smaller screw length, and smaller screw width but both similar sagittal angle and similar pedicle height when compared with trajectory A. A total of 106 pedicle screws were inserted at C7 through trajectory B and only 8 screws were displaced with the accuracy of screw placement as high as 92.5%. Conclusion In CSM patients with C3 to C6 instrumented by LMS, using trajectory B for C7 pedicle screw insertion is easy to both identify the entry point and facilitate the rod insertion.

Abstract We explored the joint effects of different metabolic obesity phenotypes on all-cause and disease-specific mortality risk among the American population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Mortality outcome data were from mortality files linked to National Death Index record and follow-up information was up to December 31, 2019. 50,013 participants were finally included. Four metabolic obesity phenotypes were defined based on obesity and metabolic status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Population-weighted Cox proportional hazards models were used to explore the all-cause and disease-specific mortality risk of metabolic obesity phenotypes. The all-cause mortality risk of MUO and MUNO was significantly higher than MHNO. MUNO was associated with a significantly increased risk of death from heart disease (HR: 1.40, 95% CI 1.16–1.70), hypertension (HR: 1.68, 95% CI 1.34–2.12), diabetes (HR: 2.29, 95% CI 1.67–3.15), and malignant neoplasms (HR:1.29, 95% CI 1.09–1.53). Metabolic unhealth significantly increased the risk of all-cause mortality, regardless of obesity status. Among individuals with metabolic unhealthy status, obesity significantly reduced the risk of all-cause mortality (HR: 0.91, 95% CI 0.85–0.98). Our study highlights the importance of identifying and characterizing metabolic obesity phenotypes in obese and metabolically abnormal patients, as well as healthy adults. Comprehensive evaluation of obesity and metabolic status is necessary to adopt appropriate interventions and treatment measures and maximize patient benefit.

Abstract Urinary tract infection (UTI) caused by spinal cord injury (SCI) can have significant morbidity. There is currently a lack of relevant data in China. This study explores incidence and risk factors of UTI in hospitalized patients with SCI in China, and will help healthcare professionals to make informed clinical decisions to reduce the incidence of UTI. This retrospective study analyzed the medical records of patients with SCI who were hospitalized at three campuses of a hospital in central China between August 2014 and August 2023. The files of patients with SCI were reviewed for demographics and clinical characteristics. Logistic regression analysis was performed to identify risk factors associated with UTI. A total of 538 patients were included in this study. The incidence of UTI was 49.8%. Sex, hypoproteinemia, urinary incontinence, bladder irrigation, timing of rehabilitation, duration of indwelling urinary catheter were risk factors of UTI. The implementation of specific preventive measures is anticipated to result in a decrease in the occurrence of UTI among individuals with SCI, consequently enhancing their overall quality of life and prognosis.

Abstract Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.

Abstract Background This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). Methods Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. Results Immunohistochemical staining showed that the tumors expressed CK7, S‐100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. Conclusion Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC.

Earthquake-induced liquefaction is a geological disaster that caused extensive damage to buildings, railways, dams. Due to the construction techniques and economic conditions, the subsurface layers of some buildings must be reinforced to resist seismic loads. Microbial-induced desaturation is a development technique which can be used for existing buildings to mitigate liquefaction. Shaking table tests were conducted to survey the effect of microbial induced desaturation on liquefaction-prone foundations beneath buildings. The test results showed that, lower saturation degree delays the generation of excess pore pressure and reduces its magnitude. It appears that the resistance to excess pressure increases as saturation degree is reduced from 100% to 93.4% or 85.6%. Desaturation prevents the decay of the amplitude of acceleration oscillations, but increases the accelerations of the structure. The settlement of the sandy soil decreases as the saturation degree decreases. Resistance to liquefaction increased by more than twice than that in the saturated sample after induced desaturation to 93.4%. The weight of the building structure contributes to the anti-liquefaction capacity.

The quantitative research on swelling properties of bentonite considering the influence of salt ions under the effect of hydrothermo-mechanical coupling is relatively weak. Based on a calculation model for the swelling characteristics of bentonite from a fractal perspective, this work proposes a novel coupled multifield control equation for unsaturated bentonite considering the influence of salt ions. The numericalization of the coupling control equation was completed by secondary development of a numerical analysis platform. The new theoretical model’s dependability and validity were validated by comparing it to experimental data. The evolution of the related-field quantities under the multifield coupled effect in salt-bearing environments was obtained, and the effect of salt ion concentration was analyzed. The calculation showed that the temperature of bentonite changed periodically with changing ambient temperature. Temperature gradient induces migratory movement of water from high to low temperature regions. The hollow axisymmetric soil sample gradually saturated from outside to inside with increasing water injection rate at the outer cylindrical surface. The swelling pressure of bentonite will increase with an increase in water content, whereas the presence of salt ions weakened the swelling behavior. Temperature and relative humidity were less affected by salt ion concentration.

Abstract Background Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti‐inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro. Methods In vitro, western blotting, real‐time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin‐1 beta (IL‐1β)‐induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture‐induced IVDD rat models. Results In vitro, API played a crucial role in anti‐inflammation and autophagy enhancement in IL‐1β‐induced NPCs. API improved inflammation by inhibiting the nuclear factor‐kappaB and mitogen‐activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3‐kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture‐induced IVDD model. Conclusions API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

BackgroundThe performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC.MethodsWe searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities.ResultsFourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89–0.94), 0.79 (95% CI 0.72–0.85), and 0.90 (95% CI 0.86–0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists.DiscussionIn conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

Abstract Iron overload is common in cardiovascular disease, it is also the factor that drives ferroptosis. Noncoding RNAs play an important role in heart disease; however, their regulatory role in iron overload‐mediated ferroptosis remains much unknown. In our study, the iron overload model in mice was constructed through a high‐iron diet, and ammonium iron citrate treatment was used to mimic iron overload in vitro. We found iron overload induced ferroptosis in cardiomyocytes, which was dependent on the high expression of transferrin receptor (TFRC). MiR‐31‐5p was downregulated during iron overload; it inhibited cardiomyocyte ferroptosis by targeting TFRC. CircPIK3C2A, a highly expressed circRNA in the heart, was upregulated when iron was overloaded. CircPIK3C2A enhanced the expression of TFRC by sponging miR‐31‐5p and promoted ferroptosis during iron overload. Our results reveal a novel mechanistic insight into noncoding RNA‐based ferroptosis and identify the circPIK3C2A/miR‐31‐5p/TFRC axis as a promising therapeutic target for myocardial damage.

Somatostatin (SST)-producing pancreatic delta-cells play an important role in maintaining the balance of insulin and glucagon secretion within the islets. This study aimed to generate a human embryonic stem cell (hESC) line with a SST-P2A-mCherry reporter using CRISPR/Cas9 system. The SST-P2A-mCherry reporter cell line was shown to maintain typical pluripotent characteristics and able to be induced into SST-producing pancreatic delta-cells. The generation of the cell line would provide useful platform for the characterization of stem cell-derived delta-cells, discovery of delta-cell surface markers and investigation of paracrine mechanisms, which will ultimately promote the drug discovery and cell therapy of diabetes mellitus.

ObjectivesThe study aims to examine the associations between exercise self-efficacy, motivation, physical activity, and body composition among emerging adults.DesignCross-sectional.MethodsA convenience sample of 147 emerging adults participated in the Releasing Weight (RELEW) project. The InBody720 analyzer was used to measure body composition, and the International Physical Activity Questionnaire-Short, the Shortened Physical Activity Self-Efficacy Scale, and the Treatment Self-Regulation Questionnaire were used to measure self-reported physical activity, self-efficacy, and motivation. Structural Equation Modeling was used to exam the complex relationships among multiple variables. in this study. The Partial least squares structural equation modeling analysis with bootstrapping in Smart PLS 3 was employed to explore the path coefficients and t-values for the relationships that were thought to exist. Significance was determined using a threshold of p < 0.05.ResultsThe mean age of 147 participants was 18.5 ± 1.87, of whom 51.7% were female, recruited for this study. Exercise self-efficacy has a significant positive correlation with exercise motivation (r = 0.220, p = 0.008) and physical activity (r = 0.279, p < 0.001). Exercise motivation does not demonstrate significant associations with physical activity (r = 0.094, p = 0.298). Utilizing SEM, the model explained 9.2% of exercise self-efficacy, 11.8% of physical activity, and 68.3% of body composition variance. Mediation analysis revealed that exercise self-efficacy partially mediated the relationship between exercise motivation and physical activity (β = 0.106, t = 2.538, p < 0.05), and physical activity partially mediated the relationship between exercise self-efficacy and body composition (β = −0.296, t = 4.280, p < 0.001).ConclusionThis study sheds light on the complex relationships among motivation, self-efficacy, physical activity and body composition during emerging adulthood. Our results highlight the mediating role of self-efficacy and its impact on physical activity behaviors, offering valuable insights for targeted interventions and policy development to improve health outcomes in this demographic.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Visual-based brain-computer interface (BCI) enables people to communicate with others by spelling words from the brain and helps professionals recognize targets in large numbers of images. P300 signals evoked by different types of stimuli, such as words or images, may vary significantly in terms of both amplitude and latency. A unified approach is required to detect variable P300 signals, which facilitates BCI applications, as well as deepens the understanding of the P300 generation mechanism. In this study, our proposed approach involves a cascade network structure that combines xDAWN and classical EEGNet techniques. This network is designed to classify target and non-target stimuli in both P300 speller and rapid serial visual presentation (RSVP) paradigms. The proposed approach is capable of recognizing more symbols with fewer repetitions (up to 5 rounds) compared to other models while possessing a better information transfer rate (ITR) as demonstrated on Dataset II (17.22 bits/min in the second repetition round) of BCI Competition III. Additionally, our approach has the highest unweighted average recall (UAR) performance for both 5 Hz ( $0.8134\pm 0.0259$ ) and 20 Hz ( $0.6527\pm 0.0321$ ) RSVP. The results show that the cascade network structure has better performance between both the P300 Speller and RSVP paradigms, manifesting that such a cascade structure is robust enough for dealing with P300-related signals (source code is available at https://github.com/embneural/Cascade-xDAWN-EEGNet-for-ERP-Detection).

Abstract Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Abstract This study aims to develop an advanced mathematic model and investigate when and how will the COVID-19 in the US be evolved to endemic. We employed a nonlinear ordinary differential equations-based model to simulate COVID-19 transmission dynamics, factoring in vaccination efforts. Multi-stability analysis was performed on daily new infection data from January 12, 2021 to December 12, 2022 across 50 states in the US. Key indices such as eigenvalues and the basic reproduction number were utilized to evaluate stability and investigate how the pandemic COVD-19 will evolve to endemic in the US. The transmissional, recovery, vaccination rates, vaccination effectiveness, eigenvalues and reproduction numbers ( $${R}_{0}$$ R 0 and $${R}_{0}^{end}$$ R 0 end ) in the endemic equilibrium point were estimated. The stability attractor regions for these parameters were identified and ranked. Our multi-stability analysis revealed that while the endemic equilibrium points in the 50 states remain unstable, there is a significant trend towards stable endemicity in the US. The study's stability analysis, coupled with observed epidemiological waves in the US, suggested that the COVID-19 pandemic may not conclude with the virus's eradication. Nevertheless, the virus is gradually becoming endemic. Effectively strategizing vaccine distribution is pivotal for this transition.

Abstract Spinal cord injuries are incredibly disabling and can have fatal consequences. At present, there is a lack of available information regarding the epidemiological characteristics of patients who have experienced spinal cord injury (SCI) in China. This retrospective hospital-based study was conducted in the Rehabilitation department of Wuhan’s Tongji Hospital between 2016 and 2022. A total of 649 individuals diagnosed with SCI (both traumatic and non-traumatic) were admitted during this period. Data regarding various epidemiological features were gathered, including sex, age, etiology, occupation, neurological level of injury, the American Spinal Injury Association Impairment Scale at the time of admission, and information on any accompanying injuries. Out of the 649 cases of SCI, there were 539 cases of traumatic SCI and 110 cases of non-traumatic SCI. The mean age at the time of injury was 45.6 ± 14.8 years. The ratio of male to female patients was higher in traumatic SCI at 2.82:1compared to non-traumatic SCI at 1.68:1. Traffic accidents were the most common cause of TSCI, accounting for (n = 207/539; 38.40%) of cases. On the other hand, neoplasm was the most common cause of NTSCI, accounting for (n = 38/110; 34.54%) of cases. The findings indicated a higher proportion of males, with traffic accidents being the main cause of injury among TSCI patients. It is crucial to prioritize the risk of falling among older adults and allocate more attention to this issue. These results emphasize the need for tailored preventive strategies that consider the unique characteristics of different types of SCI patients.

Abstract Background and aim Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear. Methods Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. Results Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. Conclusion Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit.

Purpose – The purpose of this paper is to explore the concept of data assets and how companies can assetize their data. Using the literature review methodology, the paper first summarizes the conceptual controversies over data assets in the existing literature. Subsequently, the paper defines the concept of data assets. Finally, keywords from the existing research literature are presented visually and a foundational framework for achieving data assetization is proposed. Design/methodology/approach – This paper uses a systematic literature review approach to discuss the conceptual evolution and strategic imperatives of data assets. To establish a robust research methodology, this paper takes into account two main aspects. First, it conducts a comprehensive review of the existing literature on digital technology and data assets, which enables the derivation of an evolutionary path of data assets and the development of a clear and concise definition of the concept. Second, the paper uses Citespace, a widely used software for literature review, to examine the research framework of enterprise data assetization. Findings – The paper offers pivotal insights into the realm of data assets. It highlights the changing perceptions of data assets with digital progression and addresses debates on data asset categorization, value attributes and ownership. The study introduces a definitive concept of data assets as electronically recorded data resources with real or potential value under legal parameters. Moreover, it delineates strategic imperatives for harnessing data assets, presenting a practical framework that charts the stages of “resource readiness, capacity building, and data application”, guiding businesses in optimizing their data throughout its lifecycle. Originality/value – This paper comprehensively explores the issue of data assets, clarifying controversial concepts and categorizations and bridging gaps in the existing literature. The paper introduces a clear conceptualization of data assets, bridging the gap between academia and practice. In addition, the study proposes a strategic framework for data assetization. This study not only helps to promote a unified understanding among academics and professionals but also helps businesses to understand the process of data assetization.

Abstract Background Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20–50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. Methods PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). Results Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39–10.98, p

Abstract Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor–brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.

Abstract Short‐term interval estimation can effectively and precisely quantify the uncertainties of renewable energy, accurately represent the range of fluctuations of uncertain variables in robust optimisation of electricity‐heating integrated energy system (EHIES) and it is getting crucial for reliable and flexible operation of renewable dominated new energy systems. The authors present a multivariate data‐driven short‐term PV power interval prediction model that consists of multiple layers, including one‐dimensional convolutional layer, ultra‐lightweight subspace attention mechanism (ULSAM), bidirectional long and short‐term memory (BiLSTM), quantile regression (QR) and kernel density estimation (KDE). The one‐dimensional convolutional layer and ULSAM can extract sequential features and highlight key information from the data; the BiLSTM processes time series data in both directions and conveys historical information; the QR and KDE models generate interval prediction with a given confidence level. Based on the proposed interval estimation, a refined PV uncertainty set can be established and adopted by robust optimal scheduling of EHIES utilising min‐max‐min algorithm. The simulation results have demonstrated the estimation accuracy and adaptability to various weather scenarios.

Abstract Background Human papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center. Methods A total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed. Results In both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%). Conclusion High grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China.

Abstract Background Bone fracture is a common orthopedic disease that needs over 3 months to recover. Promoting the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is beneficial for fracture healing. Therefore, this research aimed to study the roles of long non-coding RNA (lncRNA) KCNQ10T1 in osteogenic differentiation of BMSCs. Methods BMSCs were treated with osteogenic medium and assessed by CCK-8 and flow cytometry assays. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), as well as concentration of osteoblast markers were measured to evaluate osteogenic differentiation of BMSCs. Western blot was employed to detect proteins; while, qRT-PCR was for mRNA levels. Additionally, targeted relationships between KCNQ10T1 and miR-19a-3p, as well as miR-19a-3p and SMAD5 were verified by dual luciferase reporter gene assay along with RNA pull-down method. Results Upregulation of KCNQ10T1 promoted the ALP staining and ARS intensity, increased the cell viability and decreased the apoptosis rate of BMSCs. Besides, KCNQ10T1 overexpression increased the ALP, OPG, OCN and OPN protein levels. KCNQ10T1 sponges miR-19a-3p, which targets Smad5. Upregulated miR-19a-3p reversed the overexpressed KCNQ10T1-induced effects, and depletion of SMAD5 reversed the miR-19a-3p inhibitor-induced effects on osteogenic medium-treated BMSCs. Conclusions Upregulation of KCNQ10T1 promoted osteogenic differentiation of BMSCs through miR-19a-3p/SMAD5 axis in bone fracture.