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The medicine field continues to encounter obstacles in understanding the etiology of skin inflammation and the process of skin wound repair. Developing sustainable and effective three-dimensional (3D) skin models for investigating inflammatory skin biology remains a challenge. By incorporating halloysite nanotubes (HNT) into a composite collagen/alginate/hyaluronic acid hydrogel, we created a novel 3D skin model and introduced keratinocytes and fibroblast cells into it. We demonstrate that the modified 3D skin model is capable of enhancing the differentiation and adhesion behaviors of keratinocytes and fibroblast cells in vitro and promoting wound healing in vivo. These characteristics highlight the potential of this approach for the study of skin inflammation, wound healing, regeneration, aging, and beyond.

BackgroundNeedle stick injury (NSI) is one of the most common and severe occupational hazards for healthcare workers (HCWs), leading to both physical harm and psychological distress and ultimately affecting patient safety. Previous studies on NSI were predominantly focused on general clinical practice, and limited research has targeted specifical NSI occurring in acupuncture practice in China, which has the greatest use of acupuncture.ObjectiveThis study aimed to investigate NSI and associated factors among acupuncture practitioners in China.MethodsA cross-sectional online survey was conducted among acupuncture practitioners across 98 hospitals in southwest China from April to May 2024. A researcher-developed questionnaire was used to collect participants’ experiences of NSI, general information, and knowledge, behavior, and risk perception related to occupational exposure. Multivariate logistic regression was employed to examine factors associated with NSI.ResultsA total of 578 acupuncture practitioners completed the questionnaire, among whom 34.3% experienced at least one NSI in the past three years, yet 46.0% of these incidents were not reported. Factors associated with an increased risk of NSIs included postgraduate education or higher (OR = 2.174, 95% CI: 1.020, 4.634), high probability of occupational exposure (OR = 2.940, 95% CI: 1.826, 4.735), moderate perception of exposure severity (OR = 9.149, 95% CI: 1.948, 42.97), and high perception of exposure severity (OR = 7.025, 95% CI: 1.497, 32.969). Conversely, factors associated with a reduced risk of NSIs included females (OR = OR = 0.576, 95% CI: 0.379, 0.876), nurses (OR = 0.396, 95% CI: 0.210, 0.746), working in other professions (OR = 0.362, 95% CI: 0.151, 0.868), adherence to standard preventive measures (OR = 0.396, 95% CI: 0.210, 0.746), and consistent adherence to post-exposure procedures (OR = 0.092, 95% CI: 0.021, 0.398).ConclusionNSI is common among acupuncture practitioners in Chinese medical institutions, and under-reporting is significant. Our findings suggest that standard prevention strategies, adherence to exposure protocols, enhanced training, and effective reporting policies may help reduce NSI and improve reporting rates.

Abstract Background Long-term care insurance (LTCI) in China provides financial and care security for persons with disabilities and includes caregivers in the paid labour workforce. However, it is unclear how the LTCI affects health outcomes in female recipients, female caregivers, and female non-recipients and female non-caregivers. Methods Using the China Health and Retirement Longitudinal Study data and staggered difference-in-differences method, we evaluated the effect of LTCI on health outcomes in women with different roles, including female recipients, female caregivers, and female non-recipients and female non-caregivers, and discussed the heterogeneity of the effect on women’s health outcomes. Results LTCI statistically significant increased self-rated health and reduced depression in women and improved the health in women with different roles by increasing self-rated health in female recipients, reducing chronic diseases in female caregivers, and reducing depression in female non-recipients and female non-caregivers. There was a more pronounced improvement in health outcomes among women in the west and northeast and women in rural village. Conclusions After the implementation of LTCI, health outcomes in female recipients, female caregivers, and female non-recipients and female non-caregivers were improved. LTCI’ improvement on women’s health outcomes was heterogeneous geographically and socially. Our findings highlight the importance of delivering differentiated health interventions for women with different roles in the implementation process of LTCI and minimizing women’s health inequalities in geography and society.

BackgroundCDK7 has been demonstrated to play a crucial role in the initiation and progression of malignancy. Therefore, targeting CDK7, which regulates the transcription process, has emerged as a new promising approach for treating cancer. Research on CDK7 inhibitors has significantly increased over the past 2 decades, with almost 600 related papers in the Web of Science Core Collection database. To effectively identify future research hotspots and potential future directions, it is crucial to systematically review and visually present the research on this topic from a comprehensive viewpoint, ensuring scientific reliability.MethodsThis study performed bibliometric analysis via CiteSpace and VOSviewer scientometrics analysis software to examine data on the publication of articles on CDK7 inhibitors over the past 2 decades; the data included country of publication, author names, institution names, scientific categories, cited journals, and keywords related to the field of CDK7 inhibitors.ResultsThis bibliometric analysis included 426 publications from 41 different nations, referencing a total of 15,892 sources. Research associated with CDK7 inhibitors has rapidly expanded since 2016, and the US and China are the two countries with the highest publication output among the countries and institutes that produce literature on CDK7 inhibitors. Furthermore, the US is the country that most frequently engages in international cooperation. The evolution of keywords identifying antitumor strategies related to CDK7-mediated cellular transcription processes has been the research focus in recent years.ConclusionIn this study, we identified research efforts and their evolving patterns and predicted advances in the CDK7 inhibitor field. The knowledge structure of CDK7 inhibitors encompasses pharmacological mechanisms, therapeutic targets, and cancer treatment strategies. The primary objectives of contemporary research are to discover the processes underlying cancer progression, identify specific signaling pathways, and develop effective clinical medicines.

Abstract Background Policy effect might be multidimensional and spill over to non-recipients. It is unclear how the implementation of Long-Term Care Insurance (LTCI) policy affects depression in non-disabled people and how this effect differs in different non-disabled groups. Methods Using time-varying differences-in-differences method and nationally representative health survey data in wave 2011, wave 2013, wave 2015 and wave 2018 from the China Health and Retirement Longitudinal Study, we assessed the effect of LTCI policy on depression in non-disabled people aged 45 years and older, and discussed the heterogeneity of effect across different population characteristics: retirement, financial support and social participation status. Results We found LTCI policy statistically significant reduced depression by 0.76 units in non-disabled people compared to non-pilot cities. Depression in non-disabled people who unretired, with financial support and without social participation was reduced by 0.8267, 0.7079 and 1.2161 units, respectively. Conclusions Depression in non-disabled people was statistically significant reduced because of LTCI policy in China, and non-disabled people who unretired, with financial support and without social participation benefited more from LTCI policy. Our findings highlight the depression-reducing effect of LTCI policy in non-recipients and suggest that non-disabled people who unretired, with financial support and without social participation should be concerned during LTCI policy progress.

Gait impairment in Parkinson’s Disease (PD) is quantitatively assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a well-established clinical tool. Objective and efficient PD gait assessment is crucial for developing interventions to slow or halt its advancement. Skeleton-based PD gait MDS-UPDRS score estimation has attracted increasing interest in improving diagnostic efficiency and objectivity. However, previous works ignore the important cross-spacetime dependencies between joints in PD gait. Moreover, existing PD gait skeleton datasets are very small, which is a big issue in deep learning-based gait studies. In this work, we collect a sizable PD gait skeleton dataset by multi-view Azure Kinect sensors. The collected dataset contains 102 PD patients and 30 healthy older adults. In addition, gait data from 16 young adults (aged 24–50 years) are collected to further examine the effect of age on PD gait assessment. For skeleton-based automatic PD gait analysis, we propose a novel cross-spatiotemporal graph convolution network (CST-GCN) to learn complex features of gait patterns. Specifically, a gait graph labeling strategy is designed to assemble and group cross-spacetime neighbors of the root node according to the spatiotemporal semantics of the gait skeleton. Based on this strategy, the CST-GCN module explicitly models the cross-spacetime dependencies among joints. Finally, a dual-path model is presented to realize the modeling and fusion of spatial, temporal, and cross-spacetime gait features. Extensive experiments validate the effectiveness of our method on the collected dataset.

Abstract Background To alleviate the shortage of caregivers associated with disabled persons, China has implemented a pilot policy for long-term care insurance. This policy has the characteristics of "familialization" and "de-familialization" policy orientation, and it is indeed essential to clarify whether the policy has a positive spillover effect on the health of family caregivers, which is of great value to the pilot from local practice to national institutional arrangement. Methods Based on the China Health and Retirement Longitudinal Study microdata and time-varying DID method, our study used the implementation of the pilot policy as a "quasi-natural experiment" to assess the health spillover effects of the pilot policy on family spousal caregivers. Results This policy significantly improved the health of spousal caregivers, increasing self-rated health and life satisfaction, and reducing depression; Compared with female, urban and central-western spousal caregivers, male, rural and eastern spousal caregivers were "beneficiaries" in more dimensional health. Conclusions Our research indicated that spousal caregivers of disabled people, particularly male, rural and eastern spousal caregivers, experienced positive health spillovers after implementing long-term care insurance. These results suggest that the imbalance between supply and demand of nursing staff could be solved in terms of de-familialization and familialization, spousal caregivers should be promoted to equally enjoy the policy benefits on gender, urban–rural and regions.

This paper proposes a multifractal least squares support vector machine detrended fluctuation analysis (MF-LSSVM-DFA) model. The system is an extension of the traditional MF-DFA model. To address potential overfitting or underfitting caused by the fixed-order polynomial fitting in MF-DFA, LSSVM is employed as a superior alternative for fitting. This approach enhances model accuracy and adaptability, ensuring more reliable analysis results. We utilize the p model to construct a multiplicative cascade time series to evaluate the performance of MF-LSSVM-DFA, MF-DFA, and two other models that improve upon MF-DFA from recent studies. The results demonstrate that our proposed modified model yields generalized Hurst exponents h(q) and scaling exponents τ(q) that align more closely with the analytical solutions, indicating superior correction effectiveness. In addition, we explore the sensitivity of MF-LSSVM-DFA to the overlapping window size s. We find that the sensitivity of our proposed model is less than that of MF-DFA. We find that when s exceeds the limited range of the traditional MF-DFA, h(q) and τ(q) are closer than those obtained in MF-DFA when s is in a limited range. Meanwhile, we analyze the performances of the fitting of the two models and the results imply that MF-LSSVM-DFA achieves a better outstanding performance. In addition, we put the proposed MF-LSSVM-DFA into practice for applications in the medical field, and we found that MF-LSSVM-DFA improves the accuracy of ECG signal classification and the stability and robustness of the algorithm compared with MF-DFA. Finally, numerous image segmentation experiments are adopted to verify the effectiveness and robustness of our proposed method.

In recent years, the unrivalled self‐assembly properties of DNA molecules have driven the rapid development of a new class of DNA self‐assembly technology—DNA origami technology. Over the past decade, this technology has enabled the construction of DNA nanostructures with different shapes, such as 2D and 3D structures. Meanwhile, the application of DNA origami are also developed rapidly. DNA origami structures are widely used in nanomaterial preparation and drug delivery due to their characteristics of accurate addressability, excellent programmability, and good biocompatibility, especially in the field of nanomaterial preparation. Such structures provide a new platform to construct nanomaterials with high precision. Herein, the development of DNA origami technology is introduced, and the research progress of 2D and 3D DNA origami in the past two decades is systematically summarized. Then, the application of DNA origami template in nanomaterial preparation is emphasized. Finally, the main challenges and opportunities for nanomaterials fabrication based on DNA origami technology are illustrated.

Abstract Background Multiple system atrophy (MSA) associated with neuroleptic malignant-like syndrome (NMLS) is rare and few cases have been described in the literature. Case presentation In the present study, three patients with MSA associated with NMLS were analyzed from January 2012 to January 2020 to characterize their clinical presentations. Data collected from the patients for analysis included general patient history, the fluctuation and severity of disease symptoms, the indicated therapies and disease progression at follow-up. All patients had histories of sudden withdrawal or reduction of levodopa prior to the onset of symptoms. Clinical presentations were characterized by hyperthermia, autonomic dysfunction, worsening of extrapyramidal symptoms, and elevated serum creatine kinase (CK) levels. During hospitalization, one patient rapidly progressed and died, while the other two patients were successfully treated. Conclusions Early diagnosis and treatment are very important for patient outcomes in NMLS. Notably, the correct dose and time of administration of dopaminergic medication may be key in treating NMLS.

A method of designing and fabricating substrate-free Au/SiNx/Au metafilms as the terahertz (THz) absorber of metamaterial focal plane arrays (MFPA) is reported. The absorption was investigated by the finite integration method simulation and new explicit functions. The substrate-free structure was well fabricated by microelectromechanical system (MEMS) technology. The frequency-dependent absorption of MFPA was measured by THz time-domain spectroscopy (THz-TDS) system. It exhibits an extremely high absorptance of 98.7% at 1.36 THz. The absorption characteristic shows an asymmetric profile, which is well fitted with an Asymmetric Double Sigmoidal (Asym2sig) model. Our results show that the Au/SiNx/Au metafilms have potential in optical readout THz real-time imaging, and highly sensitive sensing applications.

A broadly tunable erbium-doped fiber ring laser is proposed and demonstrated based on the tapered polarization maintaining fiber (PMF) Sagnac interferometer, in which the Sagnac and intermodal interferences are superimposed to generate one localized peak over a wide wavelength range in its transmission spectrum. By heating the tapered PMF, the localized peak may be discretely tuned with the temperature at the step, depending on the intermodal interference. Tunability may become continuous when additional stress is exerted longitudinally on the tapered PMF. The tapered PMF Sagnac interferometer is inserted into the laser cavity to achieve broadly and continuously tunable output. Specifically, by optimizing the PMF length and its tapering section to obtain proper channel intervals of the Sagnac and intermodal interference, the lasing wavelength is continuously tuned over 60 nm covering from 1565.1 nm to 1625.2 nm with sidemode suppression ratio higher than 50 dB and power uniformity better than 1 dB. The tuning responses to temperature and axial stress are both linear with sensitivity of −1.1 nm/°C and −29.4 pm/μϵ. Most importantly, the temperature and axial stress affect the Sagnac and intermodal interferences, respectively, which makes it convenient to set the lasing wavelength beforehand during operation.

Background: Obsessive-compulsive disorder (OCD) is associated with psychosocial impairment, which can be exacerbated by depressive symptoms. In this study, we employed graph theory analysis to investigate the association among neuroimaging, clinical features, and psychosocial functioning in OCD patients, with a specific focus on the differential impact of depressive symptoms. Methods: 216 OCD patients were divided into two subgroups based on depressive symptoms. Resting-state functional MRI data were acquired from a subset of 106 OCD patients along with 77 matched healthy controls (HCs). We analyzed the topological characteristics of the entire brain and the cognition-related subnetworks and performed Pearson correlation analyses to further explore the relationship with psychosocial functioning. Results: OCD patients with more severe depressive symptoms exhibited greater impairment across all dimensions of psychosocial functioning. Graph theory analysis revealed more pronounced reductions in network efficiency within the entire brain, the default mode network (DMN), and the cingulo-opercular network (CON) among patients with non or mild depressive symptoms. Lower nodal efficiency and degree centrality of the right superior temporal gyrus (STG) were found in OCD patients and these variables were positively correlated with psychosocial functioning impairment. Conclusions: This study revealed that the presence of depressive symptoms generally exacerbated psychosocial functioning impairment in OCD patients. Abnormalities in the functional integration of the entire brain, the DMN, and the CON in OCD patients may comprise the basis of cognitive deficits, while dysfunction of the right STG may affect the psychosocial functioning through its role in emotion, intention perception, and insight.

Background: In this study, we sought to detect the expression of complement C3 and C4 in serum and maternal-fetal interface in patients with unexplained recurrent spontaneous abortion, and analyze their correlation, in order to explore the clinical significance and role of C3 and C4 in unexplained recurrent spontaneous abortion. Methods: In a prospective cohort study, products of conception of 20 women who underwent curettage due to unexplained recurrent spontaneous abortion in the Department of Obstetrics and Gynecology at the Sichuan Provincial People’s Hospital from December 2021 to December 2022 were chosen as the case group, and 23 healthy early-pregnancy women who underwent elective abortion due to personal reasons during the same period were chosen as the control group. Serum samples before curettage and decidual tissues samples after curettage were collected. C3 and C4 levels in serum samples were detected by immunoturbidimetry, and semi-quantitative scoring analysis was performed after immunohistochemical staining of decidual tissues samples. The correlation between C3 and C4 in serum and decidual tissues was analyzed. Results: The levels of C3 and C4 in serum and decidual tissues in the case group were significantly higher than those in the control group, and the differences were statistically significant (p < 0.05). There was a positive correlation between C3 and C4 in serum in the case group (r = 0.481, p < 0.05). There was no significant correlation between C3 and C4 in decidual tissues in the case group (p > 0.05). There was no significant correlation between C3 in serum and C3 in decidual tissues, nor between C4 in serum and C4 in decidual tissues in the case group (p > 0.05). Conclusions: The levels of C3 and C4 in serum and decidual tissues in the case group were higher than those in the healthy, normal early pregnancy women. This implies that elevated levels of activated C3 and C4 may be related to the pathogenesis of unexplained recurrent miscarriage. C3 and C4 can be used as early diagnostic criteria for recurrent miscarriage. There is a positive correlation between C3 in serum and C4 in serum in the case group, indicating that different pathways of complement activation may be involved in the pathogenic process of unexplained recurrent miscarriage.

Abstract Background The COVID-19 pandemic called for a new ethical climate in the designated hospitals and imposed challenges on care quality for anti-pandemic nurses. Less was known about whether hospital ethical climate and nurses’ ethical sensitivity were associated with care quality. This study examined the association between the perceived hospital ethical climate and self-evaluated quality of care for COVID-19 patients among anti-pandemic nurses, and explored the mediating role of ethical sensitivity in this relationship. Methods A cross-sectional study was conducted through an online survey. A total of 399 anti-pandemic nurses from ten designated hospitals in three provinces of China were recruited to fill out an online survey. Multiple linear regression analysis and a bootstrap test were used to examine the relationships between ethical climate, ethical sensitivity and care quality. Results Nurses reported mean scores of 4.43 ± 0.577 (out of 5) for hospital ethical climate, 45.00 ± 7.085 (out of 54) for ethical sensitivity, and 5.35 ± 0.661 (out of 6) for self-evaluated care quality. After controlling for covariates, perceived hospital ethical climate was positively associated with self-evaluated care quality (direct effect = 0.710, 95% confidence interval [CI] 0.628, 0.792), and was partly mediated by ethical sensitivity (indirect effect = 0.078, 95% confidence interval [CI] 0.002, 0.145). Conclusions Chinese nurses who cared for COVID-19 patients perceived high levels of hospital ethical climate, ethical sensitivity, and self-evaluated care quality. Positive perceptions of hospital ethical climate were both directly associated with a higher level of self-evaluated care quality and indirectly associated, through the mediation effect of ethical sensitivity among anti-pandemic nurses.

Abstract Background Paraneoplastic syndrome is a distant effect caused by malignant tumors, which is related to the production of cellular immune response. The nervous system is the most common involved system of paraneoplastic syndrome. It is easy to be misdiagnosed. Lung cancer is the most common cancer relating to paraneoplastic neurological syndrome (PNS). Method This study retrospectively analyzed clinical data of patients with the combination of PNS and lung cancer between January 2005 and March 2021 at Qilu Hospital of Shandong University, China. Results A total of 111 patients were diagnosed with lung cancer complicated with PNS. A total of 95 (85.6%) cases had neurological symptoms as the first symptom. Sixty‐three cases had the pathological results. A total of 43 (68.3%) of small cell lung cancer (SCLC) were diagnosed. PNS patients diagnosed with SCLC included peripheral neuropathy (15 cases, 34.9%). PNS patients diagnosed with non‐small cell lung cancer (NSCLC) included peripheral neuropathy (6 cases, 30%) and limbic encephalitis (6 cases, 30%). Anti‐Hu is popular in patients with SCLC (12 cases, 42.9%) and NSCLC (6 cases, 40%). Conclusions Most patients with PNS had neurological symptoms as the first symptom. It was more common in males. It had a higher incidence in SCLC. Peripheral neuropathy was the most common PNS associated with SCLC, followed by Lambert‐Eaton syndrome. Peripheral neuropathy and limbic encephalitis were the most common PNS associated with NSCLC. Anti‐Hu is the most common antibodies both in SCLC and NSCLC. Tumor markers do not have significant difference between different pathological types.

Objectives: To describe the professional quality of life and explore its associated factors among nurses coming from other areas of China to assist with the anti-epidemic fight in Wuhan and especially examine whether the hospital ethical climate was independently associated with nurses’ professional quality of life. Methods: A cross-sectional online survey was conducted from March 2020 to April 2020. The nurses working in Wuhan from the other parts of China were the target population. The Professional Quality of Life Scale version 5, the Hospital Ethical Climate Survey, and a basic information sheet were used to collect data. Descriptive statistics, t-test, ANOVA, Pearson correlation, and multiple linear regression analysis were used to analyze the data. Results: In total, 236 nurses participated in this study, and 219 valid questionnaires were analyzed. The average age of the participants was 31.2 ± 5.0 years. Most nurses were female (176/219; 80.4%) and married (145/219; 66.2%). In term of professional quality of life, nurses reported moderate (129/219; 58.9%) to high (90/219; 41.1%) levels of compassion satisfaction, low (119/219; 54.3%) to moderate (100/219; 45.7%) levels of burnout, and low (67/219; 36.0%) to high (10/219; 4.6%) levels of secondary traumatic stress. Regarding hospital ethical climate, nurses reported moderately high hospital ethical climates with an average score of 4.46. After controlling for socio-demographic characteristics, the multiple linear regression models showed that the hospital ethical climate subscale of “relationship with physicians” was independently associated with the compassion satisfaction (β = 0.533, P

Carbon price fluctuations significantly impact the development of industries, energy, agriculture, and stock investments. The carbon price possesses the features of nonlinearity, non-stationarity, and high complexity as a time series. To overcome the negative impact of these characteristics on prediction and to improve the prediction accuracy of carbon price series, a combination prediction model named Lp-CNN-LSTM, which utilizes both convolutional neural networks and long short-term memory networks, has been proposed. Strategy one involved establishing distinct models of CNN-LSTM and LSTM to analyze high-frequency and low-frequency carbon price sequences; the combination of output was integrated to predict carbon prices more precisely. Strategy two comprehensively considered the economic and technical indicators of carbon price sequences based on the Pearson correlation coefficient, while the Multi-CNN-LSTM model selected explanatory variables that strongly correlated with carbon prices. Finally, a predictive model for a combination of carbon prices was developed using Lp-norm. The empirical study focused on China’s major carbon markets, including Hubei, Guangdong, and Shanghai. According to the error indicators, the performance of the Lp-CNN-LSTM model was superior to individual strategy prediction models. The Lp-CNN-LSTM model has excellent accuracy, superiority, and robustness in predicting carbon prices, which can provide a necessary basis for revising carbon pricing strategies, regulating carbon trading markets, and making investment decisions.

Objective China has seen an increasing number of international students in recent years, mostly from Africa and Asia. However, little is known about these students’ HIV knowledge, sexual practices and potential HIV risk. This study aimed to describe HIV-related risk among international students.Design An online cross-sectional survey.Setting 10 universities situated in one province of China.Participants 617 international students filled out the questionnaire and 607 international students were included in this study.Primary and secondary outcome measures Socio-demographic and programme-related characteristics, HIV-related knowledge, sexual practices and other HIV/sexually transmitted infection-related variables. Logistic regression analyses were performed to examine factors associated with inconsistent condom use among international students.Result The results showed that in total, only 51.6% (313/607) of international students had adequate HIV-related knowledge, and 64.9% (394/607) reported not receiving any HIV related education or training while studying in China. Moreover, 32.3% (196/607) reported having penetrative sex including oral, vaginal and anal sex during the period in which they studied in China and among them. The proportions of inconsistent condom use in vaginal and oral intercourse while studying in China were 52.6% (50/95) and 79.5% (35/44), respectively, with casual partners, and 60% (80/129) and 91.2% (52/57) with regular partners, respectively. Female gender, being married and having multiple sexual partners were associated with inconsistent condom use.Conclusion The present study indicated that international students in one province of China have suboptimal HIV-related knowledge, significant unprotected sex, less HIV testing and less safe sex education, which highlights an urgent need to provide HIV education and related health services to international students in China.

As a neurodevelopmental disorder, autism spectrum disorder (ASD) severely affects the living conditions of patients and their families. Early diagnosis of ASD can enable the disease to be effectively intervened in the early stage of development. In this paper, we present an ASD classification network defined as CNNG by combining of convolutional neural network (CNN) and gate recurrent unit (GRU). First, CNNG extracts the 3D spatial features of functional magnetic resonance imaging (fMRI) data by using the convolutional layer of the 3D CNN. Second, CNNG extracts the temporal features by using the GRU and finally classifies them by using the Sigmoid function. The performance of CNNG was validated on the international public data—autism brain imaging data exchange (ABIDE) dataset. According to the experiments, CNNG can be highly effective in extracting the spatio-temporal features of fMRI and achieving a classification accuracy of 72.46%.

Liver hepatocellular carcinoma (LIHC) is a primary malignancy, and there is a lack of effective treatment for advanced patients. Although numerous studies exist to reveal the carcinogenic mechanism of LIHC, few studies have integrated multi-omics data to systematically analyze pathogenesis and reveal potential therapeutic targets. Here, we integrated genomic variation data and RNA-seq profiles obtained by high-throughput sequencing to define high- and low-genomic instability samples. The mutational landscape was reported, and the advanced patients of LIHC were characterized by high-genomic instability. We found that the tumor microenvironment underwent metabolic reprograming driven by mutations accumulate to satisfy tumor proliferation and invasion. Further, the co-expression network identifies three mutant long non-coding RNAs as potential therapeutic targets, which can promote tumor progression by participating in specific carcinogenic mechanisms. Then, five potential prognostic markers (RP11-502I4.3, SPINK5, CHRM3, SLC5A12, and RP11-467L13.7) were identified by examining the association of genes and patient survival. By characterizing the immune landscape of LIHC, loss of immunogenicity was revealed as a key factor of immune checkpoint suppression. Macrophages were found to be significantly associated with patient risk scores, and high levels of macrophages accelerated patient mortality. In summary, the mutation-driven mechanism and immune landscape of LIHC revealed by this study will serve precision medicine.

Abstract Background Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear. Methods Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial–mesenchymal transition (EMT) by co-interacting the TGF-β pathway was examined. Results In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-β pathway stimulated by TGF-β ligand. Conclusions The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.

Drought can seriously hinder the growth of plants, resulting in reduced crop yield and quality. At present, the tolerance of DEAD-box helicases (DHC) to abiotic stresses, such as drought, high salinity, low temperature, and high temperature, has been confirmed in a variety of plants; therefore, using DEAD-box helicases to develop stress-resistant plants has great application prospects. In this study, Brassica rapa was used as a model to explore the response of the BrDHC1 gene to drought stress by creating RNA interference and overexpressing lines in B. rapa. The mechanism of BrDHC1 involved in drought resistance was revealed by the analysis of morphological characteristics, physiological indicators, and expression analysis of related stress response genes. The results showed that the overexpression of the BrDHC1 gene was more conducive to enhancing the resilience of plants under drought stress in B. rapa. Taken together, these results confirmed BrDHC1 as a newly identified DEAD-box helicase gene that could actively regulate plant growth and development under drought stress in B. rapa.

Introduction: Studies have shown that excess formaldehyde accumulation in the brain accelerates cognitive decline in people with Alzheimer’s disease (AD). Recently, reports from our research team revealed that red light treatment (RLT) improved memory in AD mice by activating formaldehyde dehydrogenase (FDH) and thus reducing formaldehyde levels. Here, we developed a medical RLT device to investigate the safety and efficacy of this device in older adults with mild to moderate AD.Methods: This will be a randomized controlled trial (RCT) that will include 60 participants who will be recruited and randomly divided into an RLT group and a control group. The RLT group will receive RLT intervention 5 days a week for 30 min each time for 24 weeks while the control group will continue their routine treatments without RLT. All participants will undergo neuropsychological and functional assessments including the Mini-Mental State Examination, the AD assessment scale-cognitive subscale (ADAS-cog), the Geriatric Depression Scale (GDS), the Neuropsychiatric Inventory (NPI) and the Barthel Index at baseline, 12 weeks and 24 weeks. All participants will undergo functional magnetic resonance imaging (fMRI) scanning and blood/urine biomarkers tests at baseline and 24 weeks. The primary outcome will be the ADAS-cog score while the secondary outcomes will be the GDS and NPI scores. Adverse events will be recorded and treated when necessary. Both an intention-to-treat analysis and a per-protocol analysis will be performed to evaluate the safety and efficacy of RLT.Discussion: This protocol outlines the objectives of the study and explained the RLT device developed by the research team. The study is designed as an RCT to evaluate the safety and effects of the RLT device on older adults with mild to moderate AD. This study will provide evidence for the clinical use of RLT on treatment for AD.Clinical Trial Registration:www.ClinicalTrials.gov, ChiCTR1800020163; Pre-results.

PARP proteins are highly conserved homologs among the eukaryotic poly (ADP-ribose) polymerases. After activation, ADP-ribose polymers are synthesized on a series of ribozymes that use NAD+ as a substrate. PARPs participate in the regulation of various important biological processes, such as plant growth, development, and stress response. In this study, we characterized the homologue of PARP1 in B. rapa using RNA interference (RNAi) to reveal the underlying mechanism responding to drought stress. Bioinformatics and expression pattern analyses demonstrated that two copy numbers of PARP1 genes (BrPARP1.A03 and BrPARP1.A05) in B. rapa following a whole-genome triplication (WGT) event were retained compared with Arabidopsis, but only BrPARP1.A03 was predominantly transcribed in plant roots. Silencing of BrPARP1 could markedly promote root growth and development, probably via regulating cell division, and the transgenic Brassica lines showed more tolerance under drought treatment, accompanied with substantial alterations including accumulated proline contents, significantly reduced malondialdehyde, and increased antioxidative enzyme activity. In addition, the findings showed that the expression of stress-responsive genes, as well as reactive oxygen species (ROS)-scavenging related genes, was largely reinforced in the transgenic lines under drought stress. In general, these results indicated that BrPARP1 likely responds to drought stress by regulating root growth and the expression of stress-related genes to cope with adverse conditions in B. rapa.

Node importance is a key factor affecting the overall operation efficiency of a railway freight transportation network (RFTN) that can be measured with the indicators of Hub and PageRank. Based on complex network theory and the national railway cargo exchange data of China’s provinces, this study constructs an RFTN model with the 31 provinces as the nodes and measures the values of Hub and PageRank for the 31 provinces. Then, the time evolution law of the importance of the provincial nodes is analyzed comprehensively, and, using a regression model, the influencing factors of the importance of the provincial nodes are identified. The results show the following. (1) The uneven distribution of natural resources will affect the spatial changes in the importance of RFTN nodes. The Hub values tended to cluster around the average, and the economic structure of the output-oriented provinces improved as a whole. At the same time, the PageRank values of many provinces in the central and western regions significantly increased, and those provinces exhibited more frequent exchanges of goods with other provinces and closer economic ties with other regions. (2) The traffic fixed asset investments and the population density have the most obvious influences on the importance of the provincial nodes with a positive effect. In contrast, the railway freight concentration (RFC) coefficient, geographical location (longitude and latitude), and coastal region all have negative effects on the importance of provincial nodes. The results of this study provide scientific decision-making support for the reasonable establishment and distribution of RFTN hubs in China.

DOI：10.3969/j.issn.1672-6731.2011.02.011

We study the global well-posedness and uniform boundedness of a two-dimensional reaction–advection–diffusion system with nonlinear advection. This strongly coupled system of nonlinear partial differential equations represents the continuum of a 2D lattice model designed to describe residential burglary, where each location is characterised by a tractability value that varies in both space and time. We show that the model with sublinear advection enhancement is globally well-posed, with a unique solution that is classical and uniformly bounded in time. Our results provide valuable insights into the development of urban crime models with nonlinear advection enhancements, making them suitable for broader applications, including nonlocal or heterogeneous near-repeat victimisation effects.