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.

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.

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.

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.

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.

Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation.

In mammals, active DNA demethylation involves oxidation of 5-methylcytosine (5mC) into 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by Tet dioxygenases and excision of these two oxidized bases by thymine DNA glycosylase (TDG). Although TDG is essential for active demethylation in embryonic stem cells and induced pluripotent stem cells, it is hardly expressed in mouse zygotes and dispensable in pronuclear DNA demethylation. To search for other factors that might contribute to demethylation in mammalian cells, we performed a functional genomics screen based on a methylated luciferase reporter assay. UNG2, one of the glycosylases known to excise uracil residues from DNA, was found to reduce DNA methylation, thus activating transcription of a methylation-silenced reporter gene when co-transfected with Tet2 into HEK293T cells. Interestingly, UNG2 could decrease 5caC from the genomic DNA and a reporter plasmid in transfected cells, like TDG. Furthermore, deficiency in Ung partially impaired DNA demethylation in mouse zygotes. Our results suggest that UNG might be involved in Tet-mediated DNA demethylation.

[Diagnostic value of combining detection of human epididymis protein 4 and CA125 in patients with malignant ovarian carcinoma].

OBJECTIVE: To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma. METHODS: To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers. RESULTS: The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women. CONCLUSIONS: HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers.

[Studies on cyclodextrin inclusion complexes of Dragon's blood and its tablets preparation].

OBJECTIVE: To study the cyclodextrin inclusion complexes of Dragon's blood for improving the drug solubility and the preparation. METHOD: The inclusion complexes were prepared with beta-cyclodextrin, HP-beta-cyclodextrin, SBE-beta-cyclodextrin and confirmed by DTA. The activity of the inclusion complex was tested by animal experiments. Inclusion complexes tablets were prepared and the dissolution test was performed. RESULT: The solubility of inclusion complexes was increased to 13. 75-168. 39 times. The activity of the inclusion complex was markedly improved, and dissolution rate was 78.69%. CONCLUSION: The cyclodextrin inclusion complexes of Dragon's blood have a good solubility, dissolution rate and pharmacological activity.