Hydrophilic 1T-WS2 Nanosheet Arrays toward Conductive Textiles for High-Efficient and Continuous Hydroelectric Generation and Storage.

Flexible hydroelectric generators (HEGs) are promising self-powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous operating voltage and superior current density remains a significant challenge. Herein, a textile-based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T-WS2@CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen-containing functional groups, which enhances the proton concentration gradients toward high-performance wearable HEGs. The vertically staggered 1T-WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture-induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm-2, an open-circuit voltage (Voc) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm-2. This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.

Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.

DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development.

Vertical Phase-Engineering MoS2 Nanosheet-Enhanced Textiles for Efficient Moisture-Based Energy Generation.

Flexible moisture-electric generators (MEGs) capture chemical energy from atmospheric moisture for sustainable electricity, gaining attention in wearable electronics. However, challenges persist in the large-scale integration and miniaturization of MEGs for long-term, high-power output. Herein, a vertical heterogeneous phase-engineering MoS2 nanosheet structure based silk and cotton were rationally designed and successfully applied to construct wearable MEGs for moisture-energy conversion. The prepared METs exhibit ∼0.8 V open-circuit voltage, ∼0.27 mA/cm2 current density for >10 h, and >36.12 µW/cm2 peak output power density, 3 orders higher than current standards. And the large-scale device realizes a current output of 0.145 A. An internal phase gradient between the 2H semiconductor MoS2 in carbonized silks and 1T metallic MoS2 in cotton fibers enables a phase-engineering-based heterogeneous electric double layer functioning as an equivalent parallel circuit, leading to enhanced high-power output. Owing to their facile customization for seamless adaptation to the human body, we envision exciting possibilities for these wearable METs as integrated self-power sources, enabling real-time monitoring of physiological parameters in wearable electronics.

Point clouds segmentation of rapeseed siliques based on sparse-dense point clouds mapping.

In this study, we propose a high-throughput and low-cost automatic detection method based on deep learning to replace the inefficient manual counting of rapeseed siliques. First, a video is captured with a smartphone around the rapeseed plants in the silique stage. Feature point detection and matching based on SIFT operators are applied to the extracted video frames, and sparse point clouds are recovered using epipolar geometry and triangulation principles. The depth map is obtained by calculating the disparity of the matched images, and the dense point cloud is fused. The plant model of the whole rapeseed plant in the silique stage is reconstructed based on the structure-from-motion (SfM) algorithm, and the background is removed by using the passthrough filter. The downsampled 3D point cloud data is processed by the DGCNN network, and the point cloud is divided into two categories: sparse rapeseed canopy siliques and rapeseed stems. The sparse canopy siliques are then segmented from the original whole rapeseed siliques point cloud using the sparse-dense point cloud mapping method, which can effectively save running time and improve efficiency. Finally, Euclidean clustering segmentation is performed on the rapeseed canopy siliques, and the RANSAC algorithm is used to perform line segmentation on the connected siliques after clustering, obtaining the three-dimensional spatial position of each silique and counting the number of siliques. The proposed method was applied to identify 1457 siliques from 12 rapeseed plants, and the experimental results showed a recognition accuracy greater than 97.80%. The proposed method achieved good results in rapeseed silique recognition and provided a useful example for the application of deep learning networks in dense 3D point cloud segmentation.

MIX-NET: Deep Learning-Based Point Cloud Processing Method for Segmentation and Occlusion Leaf Restoration of Seedlings.

In this paper, a novel point cloud segmentation and completion framework is proposed to achieve high-quality leaf area measurement of melon seedlings. In particular, the input of our algorithm is the point cloud data collected by an Azure Kinect camera from the top view of the seedlings, and our method can enhance measurement accuracy from two aspects based on the acquired data. On the one hand, we propose a neighborhood space-constrained method to effectively filter out the hover points and outlier noise of the point cloud, which can enhance the quality of the point cloud data significantly. On the other hand, by leveraging the purely linear mixer mechanism, a new network named MIX-Net is developed to achieve segmentation and completion of the point cloud simultaneously. Different from previous methods that separate these two tasks, the proposed network can better balance these two tasks in a more definite and effective way, leading to satisfactory performance on these two tasks. The experimental results prove that our methods can outperform other competitors and provide more accurate measurement results. Specifically, for the seedling segmentation task, our method can obtain a 3.1% and 1.7% performance gain compared with PointNet++ and DGCNN, respectively. Meanwhile, the R2 of leaf area measurement improved from 0.87 to 0.93 and MSE decreased from 2.64 to 2.26 after leaf shading completion.

Effect of mixed magnetic field on physical properties of atmospheric suspended fine particles.

In recent years, the fine particles suspended in the atmosphere, especially the particle size less than 10 µ m , have caused very adverse effects on the climate environment and human health. However, the current research on the causes of air pollution mainly focuses on human activities and weather conditions. Considering the weak magnetism and chargeability of atmospheric fine particles, this study proposed a new view that space electromagnetic radiation may affect the physical properties of fine particles. We first analyzed the dynamic characteristics of magnetic micro-particle in the electromagnetic environment, and built a simulation model in the COMSOL simulation software. Finally, based on the theoretical analysis and simulation results, we built an experimental verification system to evaluate the effects of electromagnetic radiation on the physical properties of micro-particle, and carried out a 30-day control experiment. The experimental results showed that the physical properties such as particle size distribution, mass concentration, and morphology of suspended fine particles in the atmosphere under electromagnetic radiation are significantly different from those under non-electromagnetic radiation environment. It can be inferred that the aggregation, fusion, and deposition of suspended particles in the atmosphere are closely related to the complex electromagnetic environment in space.

Clinical Evaluation of Efficacy on Ultrasound Combined with Neuromuscular Electrical Stimulation in Treating Lumbar Disc Herniation.

Purpose: To investigate the clinical efficacy of ultrasound (US) combined with neuromuscular electrical stimulation (NMES) in treating lumbar disc herniation (LDH) and its effect on the level of inflammatory factors. Methods: The data of 240 patients with LDH treated at our hospital from January 2020 to February 2021 were reviewed and classified into an US combined with NMES treatment group (US+NMES, n = 80), NMES only treatment group (NMES, n = 80), and US only treatment group (US, n = 80). Their Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores, levels of inflammatory factors and pain mediators, recovery rate, and total recovery time before and after treatment were compared. Additionally, the incidence of complications/adverse reactions was also investigated. Results: Compared with data before treatment, the three groups had lower VAS and ODI scores, inflammatory factor levels (interleukin- [IL-] 1, IL-6, and tumor necrosis factor- [TNF-] α), and pain mediators (transforming growth factor- [TGF-] ß1, prostaglandin E2 [PEG2], and 5-hydroxytryptamine [5-HT]) after treatment, with the most significant decrease observed in the US+NMES group. Compared with patients who received US or NMES treatment alone, patients from the US+NMES had faster recovery time and lower incidence of complications/adverse reactions. Conclusion: Collectively, US combined with NMES was associated with significant relief in pain and lumbar dysfunction and reduced local inflammatory response and pain mediator levels in LDH patients, suggesting that this combined approach could achieve better efficacy than US or NMES alone.

Cost-effectiveness comparisons of enhanced recovery after surgery (ERAS) vs. non-ERAS for esophageal cancer in China: a retrospective comparative cohort study.

Background: Esophageal cancer is a malignant tumor that seriously endangers human health. Compared with surgery alone, enhanced recovery after surgery (ERAS) has been widely used in clinical practice because it can improve perioperative care, minimize complications, and accelerate the recovery of esophageal cancer patients. However, there is a lack of data supporting the cost-effectiveness of ERAS. Methods: This retrospective cohort study included 968 esophageal cancer patients according to the pre-determined inclusion and exclusion criteria. Based on the Chinese expert consensus and guidelines, we improved the ERAS protocols consisting of 17 core measures. Subjects receiving >60% of the ERAS optimization measures were classified as the ERAS group, while those receiving <60% were classified as the pre-ERAS group. The demographic information, clinical and cost data of these patients were collected from the medical records. Based on the data distribution, the clinical effects and costs between the two groups were examined using the independent-sample t-test, the rank sum test, or the chi-square test. The effect of cost-effectiveness ratio calculation was measured by the disease cure rate obtained from the discharge report. Results: A total of 374 and 594 patients were included in the ERAS and pre-ERAS groups, respectively, and there were no significant differences in gender, American Society of Anesthesiologists (ASA) grade, tumor location, tumor stage, and other basic conditions between the two groups. The intraoperative blood loss, hospital stays, postoperative rehabilitation time, postoperative complications, and the number of secondary admissions within 30 days postoperatively of the ERAS group were lower than those of the pre-ERAS group (P<0.05). Compared with the pre-ERAS group, participants in the ERAS group had lower direct medical cost, direct non-medical cost, and indirect cost (P<0.05). Moreover, the cost-effectiveness ratio of the ERAS group (118,439.0 Yuan) was lower than that of the pre-ERAS group (143,369.0 Yuan) with respect to the cure rate. Conclusions: The study demonstrated that compared with pre-ERAS, the application of ERAS in esophageal cancer patients may accelerate postoperative rehabilitation, reduce the length of hospital stays and postoperative complications, and have better cost-effectiveness, highlighting the potential of ERAS to improve the quality of medical care.

Incidence and mortality of lung cancer in 2018 and the temporal trends from 2010 to 2018 in Henan province, China: a population-based registry study.

Background: The disease burden of lung cancer is high in Henan province, China, it is out of the utmost significance to figure the current epidemic status and temporal trend of lung cancer for effective prevention and control. Methods: The qualified data was obtained from the Henan Provincial Central Cancer Registry of China, covering 30.51% of the whole population. Incidence, mortality, proportions, and cumulative rates (among patients aged 0-74 years old) of lung cancer by areas, sex and age groups were estimated. The world Segi's standard population was applied to calculate the age-standardized rate. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate temporal trends from 2010 to 2018. Results: In 2018, there were about 55,344 new cases of lung cancer in Henan province, with the crude incidence of 50.75/100,000, the age-standardized incidence rate by world standard (Segi's) population (ASIRW) of 37.14/100,000, and the cumulative rate of 4.57%. About 41,782 people died from lung cancer in 2018, with the crude mortality rate of 38.31/100,000, the age-standardized mortality rate by world standard (Segi's) population (ASMRW) of 27.09/100,000, and the cumulative rate of 3.22%. The age-specific incidence and mortality of lung cancer increased gradually as age increased and reached the peak at the age of 85+ years. The overall ASIRW (AAPC =0.3, P=0.531) and ASMRW (AAPC =-0.2, P=0.687) remained stable from 2010 to 2018, but decreased in urban areas from 2014 to 2018 (APC for ASIRW =-4.7, P=0.023; APC for ASMRW =-5.3, P=0.012). From 2010 to 2018, the incidence rate increased in the rural population aged 75+ years old (AAPC =4.2, P=0.023). Conclusions: The incidence and mortality rates of lung cancer significantly decreased in urban areas partly due to the Cancer Screening Program in Urban China. Nonetheless, the disease burden remains high, especially in males and elderly population. Comprehensive prevention and control programs, such as smoking cessation intervention, screening, early diagnosis and early treatment programs, need to be implemented to reduce the burden of lung cancer.

Incidence and mortality of gastric cancer in 2018 and their trends from 2010 to 2018 in Henan Province, China: results from a provincial population-based cancer registry.

Background: Endoscopic screening program was carried out in Henan Province, China to reduce the large gastric cancer burden, and its effect evidence is insufficient. Knowledge on current status and time-trend of gastric cancer is need for policy makers to optimize the strategy of gastric cancer control. Methods: Gastric cancer data were pooled from registries in the Henan Cancer Registration System which may reflect the whole province cancer incidence and mortality. The pooled registration data, stratified by area (urban/rural), gender, and age groups, was combined with the provincial population data to estimate the incidence and mortality of gastric cancer in Henan Province. The Segi's world standard population was applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the time-trend in the incidence and mortality. Results: Gastric cancer was diagnosed in 33,971 patients in 2018, ranking second among all cancers. The crude incidence and age-standardized incidence rate (ASIRW) per 100,000 population were 31.15 and 23.05, respectively. In 2018, there were an estimated 25,921 gastric cancer-related deaths, ranking second among all cancer-related deaths. The crude mortality rate and age-standardized mortality rate by world standard population (ASMRW) were respectively 23.77 and 16.80 per 100,000 population. Gender and geographical differences were observed. Notably, the ASIRW and ASMRW were higher in males than females and higher in rural areas than urban areas. For ASIRW and ASMRW, the male to female ratio was 2.50 and 2.71, respectively, and the rural to urban ratio was 1.23 and 1.24, respectively. Declines in the incidence [average annual percent change (AAPC): -3.9%, P=0.001] and mortality (AAPC: -3.1%, P=0.004) of gastric cancer were observed in rural areas due to declines in the incidence and mortality among residents aged 40-69 years. The overall trend of ASIRW and ASMRW were observed to decline with AAPCs of -3.5% (P=0.003) and -2.8% (P=0.007), respectively. Conclusions: Gastric cancer incidence and mortality decreased in Henan Province, China, from 2010 to 2018, which may due to the implementation of endoscopic screening for gastric cancer in rural areas. The disease burden, however, remains high, and screening strategies and measures to reduce it should be strengthened.

Analysis of the factors influencing teamwork among oncology nurses based on multigroup structural equation model.

Background: Effective teamwork among nurses could help reduce patient mortality and improve patient satisfaction. Previous studies have revealed factors influencing nursing teamwork, including internal factors, types of hospitals and departments, demographic factors of nurses, and scheduling. However, the factors influencing teamwork among oncology nurses have not yet been analyzed in domestic studies. This study investigated the status quo and influencing factors of teamwork among oncology nurses in order to inform strategies for improving clinical treatment effect and survival time of cancer patients. Methods: Nurses from the oncology department were recruited through convenience sampling. The survey tools included a general information questionnaire, professional identity scale, missed nursing care scale, and nursing teamwork scale. SPSS 25.0 and Amos 24.0 were used to verify the reliability and validity of each scale and to modify them. A structural equation model was constructed to analyze the model fit and each path coefficient. The structural equation model was used to analyze the factors influencing nursing teamwork in the oncology department, and a multigroup structural equation model was used to analyze whether the degree of nurses' participation in enhanced recovery after surgery (ERAS) was a moderating variable of nursing teamwork. Results: A total of 583 valid questionnaires were collected from participants, and the total score for nursing teamwork was 126.86±15.62. The comprehensive influence path coefficients of professional identity and missed nursing care on nursing teamwork were as follows: team leadership (0.454) > trust and support (0.407) > team mental model (0.348). The coefficients of structural path H4 (professional identity → trust and support), H5 (professional identity → team leadership), and H7 (missed nursing care → team mental model) in the 2 group structural equation models based on the degree of nurses' participation in ERAS showed significant differences [Δχ2 =7.033, Degrees of freedom (DF)=4, P=0.000]. Conclusions: The professional identity of oncology nurses had a direct positive impact on team leadership, trust and support, team mental model, and missed nursing care. The degree of nursing staff's participation in ERAS had a moderating effect on nursing teamwork.

A cluster randomized controlled trial to evaluate the efficacy of esophageal and gastric cancer screening in mortality reduction in a non-high-incidence area: methodology and initial results.

Background: A cluster randomized controlled trial of endoscopy-based screening for esophageal cancer (EC) and gastric cancer (GC) was conducted to evaluate the efficacy and feasibility of this strategy in a non-high-incidence rural area of China. The trial design and baseline findings are presented here. Methods: A total of 33 eligible villages in Luoshan County in Henan Province were assigned randomly to the intervention or control group in a 1:1 ratio by a computer-generated randomization list. Local residents aged 40 to 69 years were enrolled from the villages. Participants in the intervention group were risk-stratified with a questionnaire, and high-risk individuals were subsequently screened by endoscopy. The primary outcomes were EC and GC mortality. The secondary outcomes comprised the detection rate, stage distribution, and the treatment rate. In this study, baseline characteristics were assessed by a questionnaire. Multivariate logistic regression analysis was performed to explore factors associated with endoscopy compliance. Results: Trial recruitment was completed in 2017, and ultimately, there were 12,475 and 11,442 participants allocated to the intervention (17 clusters) and the control group (16 clusters), respectively. We included 23,653 participants in the analysis, with 12,402 in the intervention group and 11,251 in the control group. A total of 6,286 (50.7%) participants in the intervention group were estimated as high-risk individuals, and 2,719 (43.3%) underwent endoscopy. Multivariate logistic regression analysis demonstrated that some factors including age, gender, education, personality and mental health, and upper gastrointestinal diseases or symptoms might affect endoscopy compliance. The detection rates for positive cases of EC and GC were 0.22% and 0.55%, respectively. The rates for esophageal and gastric precancerous lesions were 0.70% and 2.35%, respectively. The early detection rates for EC and GC were 50.0% and 33.3%, respectively. Additionally, the overall treatment rate for positive cases was 90.0%. Conclusions: The diagnostic yield of endoscopy-based screening for EC and GC was relatively low in a non-high-incidence rural area. The study may offer clues for the improvement of endoscopy compliance and the optimization of screening strategies for upper gastrointestinal cancer in non-high-incidence areas. Trial Registration: Chinese Clinical Trial Registry ChiCTR-EOR-16008577.

Time-trend of the incidence and mortality of esophageal cancer from 2010 to 2018 and its statistics in 2018 in Henan, China.

Background: It is great of significance to figure the time-trend of esophageal cancer (EC) and its current status for effective prevention and control, especially in EC high risk areas. As one of world-renowned high-risk areas, the epidemiology of EC in Henan has not been recently updated. Therefore, we aimed to depict the status quo of EC and analyze its time-trend in Henan. Methods: The EC data were extracted from the Henan Provincial Cancer registry database derived from the population based cancer registry system, which covered 30.51% of the whole population in Henan and were qualified according to national and international guidelines. The incidence and mortality of EC were estimated by area (rural/urban), gender, and age groups. The age-standardized rates (ASRs) were calculated according to the Segi's population. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate the time-trend of EC. Results: As estimated, there were 29,913 new EC cases in Henan, 2018. The crude incidence and the age-standardized incidence rate by world standard population (ASIRW) was 27.43/105 and 19.96/105, respectively. The incidence in males and rural was 1.83 and 1.51 times higher than that in females and urban areas, respectively. Meanwhile, it was estimated that 22,688 deaths occurred in 2018. The crude mortality and the age-standardized mortality rate by world standard population (ASMRW) were 20.80/105 and 14.47/105, respectively. Similarly, males and rural areas had higher mortality compared with females and urban areas. The age-specific incidence and mortality of EC showed significant increasing after 60-64 years group. In general, the time-trend of incidence (APC: -8.9, P<0.001) and mortality (APC: -7.6, P<0.001) of EC showed a significant decreasing trend since 2014, and downward trend were also observed in rural areas for incidence (APC: -5.2, P<0.001) and mortality (APC: -3.9, P<0.001) from 2010 to 2018. Conclusions: The EC incidence and mortality in Henan has exhibited a significant declining trend in past years. Nonetheless, the disease burden remains high, especially in males and rural areas. Therefore, the ongoing prevention and control strategies of EC should be maintained alongside the establishment of more effective strategies.

End-to-End Point Cloud Completion Network with Attention Mechanism.

We propose a conceptually simple, general framework and end-to-end approach to point cloud completion, entitled PCA-Net. This approach differs from the existing methods in that it does not require a "simple" network, such as multilayer perceptrons (MLPs), to generate a coarse point cloud and then a "complex" network, such as auto-encoders or transformers, to enhance local details. It can directly learn the mapping between missing and complete points, ensuring that the structure of the input missing point cloud remains unchanged while accurately predicting the complete points. This approach follows the minimalist design of U-Net. In the encoder, we encode the point clouds into point cloud blocks by iterative farthest point sampling (IFPS) and k-nearest neighbors and then extract the depth interaction features between the missing point cloud blocks by the attention mechanism. In the decoder, we introduce a new trilinear interpolation method to recover point cloud details, with the help of the coordinate space and feature space of low-resolution point clouds, and missing point cloud information. This paper also proposes a method to generate multi-view missing point cloud data using a 3D point cloud hidden point removal algorithm, so that each 3D point cloud model generates a missing point cloud through eight uniformly distributed camera poses. Experiments validate the effectiveness and superiority of PCA-Net in several challenging point cloud completion tasks, and PCA-Net also shows great versatility and robustness in real-world missing point cloud completion.

[Analysis of CHD7 gene variants in 22 patients with idiopathic hypogonadotropic hypogonadism].

OBJECTIVE: To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing (WES) and Sanger method were used for variant analysis and verification. RESULTS: Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c.307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T (p.Arg2319Leu) and c.3145A>T (p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+PP1+PM2, PM2+PM6+PP2+PP3, PM2+PM5+PM6+PP2+PP3 and PM2+PM6+PP2+PP3), the remaining 14 cases of IHH patients had negative genetic screening. CONCLUSION: CHD7 gene variants may be related to IHH disease.

Status and associated factors of cross-regional healthcare-seeking among patients with advanced colorectal cancer in China: a multicenter cross-sectional study.

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services. Methods: From March 2020 to March 2021, a cross­sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4. Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care. Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services.

Real-time holographic quantitative measurement of vapor density distribution of suspended droplets.

We applied digital holography (DH) technology in a quantitative measurement of the density distribution of a low refractive index transparent substance (e.g., the vapor of suspended droplets). An optical setup was built based on the Mach-Zehnder interferometer. A measurement performance test showed the mean relative error of the measurement error was about 2.0%; that of the environment disturbance error was about 0.47%. By a quantitative method to assess the precision limit, the temperature measurement precision could achieve 0.01°C, and the vapor density measurement precision could achieve 0.0001kg/m3. We believe that all the benefits above make the setup a good choice for application in the Chinese space station.

TGF-ß blockade-improved chemo-immunotherapy with pH/ROS cascade-responsive micelle via tumor microenvironment remodeling.

Immunosuppressive tumor microenvironment and low delivery efficiency severely impede the tumor chemotherapy effect. To address this issue, we develop a pH/ROS cascade-responsive prodrug micelle to deliver siTGF-ß with size-shrinkage and charge-reversal property, leading to synergistical tumor microenvironment remodeling. The nanosystem highly improved endocytosis efficiency and tumor penetration depth through charge reversal and size reduction upon exposure to weakly acidic tumor microenvironment. Moreover, the nanocarrier would rapidly escape from endo/lysosome, disassemble and release siTGF-ß and hydroxycamptothecin in response to high intracellular ROS. Furthermore, the nanosystem significantly boosted antitumor immune response and reduced immune tolerance with remodeling tumor microenvironment, which significantly prolonged the survival time of tumor-bearing mice (75% survival rate upon 35 days). It is realized by the combined effects of chemotherapy-enhanced immunogenicity and recruitment of effector T cells, TGF-ß-blockade immunotherapy-activated inhibition immunosuppressive tumor microenvironment and epithelial-to-mesenchymal transition (EMT), and regulation physical tumor microenvironment via reducing the dense tumor extracellular matrix and the high tumor interstitial pressure obstacles. To this end, the nanosystem not only overcame biobarriers and reinforced antitumor immune response, but also effectively inhibited tumor growth, metastasis and recurrence in vivo.

Phosphorylation of Tet3 by cdk5 is critical for robust activation of BRN2 during neuronal differentiation.

Tet3 regulates the dynamic balance between 5-methylcyotsine (5mC) and 5-hydroxymethylcytosine (5hmC) in DNA during brain development and homeostasis. However, it remains unclear how its functions are modulated in a context-dependent manner during neuronal differentiation. Here, we show that cyclin-dependent kinase 5 (cdk5) phosphorylates Tet3 at the highly conserved serine 1310 and 1379 residues within its catalytic domain, changing its in vitro dioxygenase activity. Interestingly, when stably expressed in Tet1, 2, 3 triple-knockout mouse embryonic stem cells (ESCs), wild-type Tet3 induces higher level of 5hmC and concomitant expression of genes associated with neurogenesis whereas phosphor-mutant (S1310A/S1379A) Tet3 causes elevated 5hmC and expression of genes that are linked to metabolic processes. Consistent with this observation, Tet3-knockout mouse ESCs rescued with wild-type Tet3 have higher level of 5hmC at the promoter of neuron-specific gene BRN2 when compared to cells that expressed phosphor-mutant Tet3. Wild-type and phosphor-mutant Tet3 also exhibit differential binding affinity to histone variant H2A.Z. The differential 5hmC enrichment and H2A.Z occupancy at BRN2 promoter is correlated with higher gene expression and more efficient neuronal differentiation of ESCs that expressed wild-type Tet3. Taken together, our results suggest that cdk5-mediated phosphorylation of Tet3 is required for robust activation of neuronal differentiation program.