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Abstract Background The spatiotemporal epidemiological evidence supporting joint endoscopic screening for esophageal cancer (EC) and gastric cancer (GC) remains limited. This study aims to identify combined high-risk regions for EC and GC and determine optimal areas for joint and separate endoscopic screening. Methods We analyzed the association of incidence trends between EC and GC in cancer registry areas across China from 2006 to 2016 using spatiotemporal statistical methods. Based on these analyses, we divided different combined risk regions for EC and GC to implement joint endoscopic screening. Results From 2006 to 2016, national incidence trends for both EC and GC showed a decline, with an average annual percentage change of -3.15 (95% confidence interval [CI]: -5.33 to -0.92) for EC and -3.78 (95% CI: -4.98 to -2.56) for GC. A grey comprehensive correlation analysis revealed a strong temporal association between the incidence trends of EC and GC, with correlations of 79.00% (95% CI: 77.85 to 80.14) in males and 77.62% (95% CI: 76.50 to 78.73) in females. Geographic patterns of EC and GC varied, demonstrating both homogeneity and heterogeneity across different regions. The cancer registry areas were classified into seven distinct combined risk regions, with 33 areas identified as high-risk for both EC and GC, highlighting these regions as priorities for joint endoscopic screening. Conclusion This study demonstrates a significant spatiotemporal association between EC and GC. The identified combined risk regions provide a valuable basis for optimizing joint endoscopic screening strategies for these cancers.

Abstract The combination of anti-angiogenic treatment and immunotherapy presents a promising strategy against colon cancer. Interleukin-17F (IL-17F) emerges as a critical immune cell cytokine expressed in colonic epithelial cells, demonstrating potential in inhibiting angiogenesis. In order to clarify the roles of IL-17F in the colon cancer microenvironment and elucidate its mechanism, we established a mouse colon carcinoma cell line CT26 overexpressing IL-17F and transplanted it subcutaneously into syngeneic BALB/c mice. We also analyzed induced colon tumor in IL-17F knockout and wild type mice. Our results demonstrated that IL-17F could suppress colon tumor growth in vivo with inhibited angiogenesis and enhanced recruitment of cysteine-cysteine motif chemokine receptor 6 (CCR6) positive immune cells. Additionally, IL-17F suppressed the tube formation, cell growth and migration of endothelial cells EOMA in vitro. Comprehensive bioinformatics analysis of transcriptome profiles between EOMA cells and those treated with three different concentrations of IL-17F identified 109 differentially expressed genes. Notably, a potential new target, Caspase 4, showed increased expressions after IL-17F treatment in endothelial cells. Further molecular validation revealed a novel downstream signaling for IL-17F: IL-17F enhanced Caspase 4/GSDMD signaling of endothelial cells, CT26 cells and CT26 transplanted tumors, while IL-17F knockout colon tumors exhibited decreased Caspase 4/GSDMD signaling. The heightened expression of the GSDMD N-terminus, coupled with increased cellular propidium iodide (PI) uptake and lactate dehydrogenase (LDH) release, revealed that IL-17F promoted pyroptosis of endothelial cells. Altogether, IL-17F could modulate the colon tumor microenvironment with inhibited angiogenesis, underscoring its potential as a therapeutic target for colon cancer.

Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research.

Abstract Carbon fiber composites are emerging as a promising new biomaterial for chest wall reconstruction implants due to their mechanical properties and biocompatibility. This work evaluates the biomechanics of carbon fiber artificial ribs using finite element analysis and clinical implementation. Static simulations of normal breathing process show the maximum stress on the implant is only 2.83 MPa, far below the material ultimate strength of 60 MPa, indicating the excellent fit for maintaining respiratory function. Dynamic collision simulations demonstrate the artificial rib model could withstand a 4 kg rigid object impact at 2 m/s without fracture. Reconstructing the artificial rib with a human rib in the finite element analysis model increases the overall stress tolerance. The impact force required for fracture increases 48% compared to the artificial rib alone, suggesting improved strength from rib integration. Clinically, 10 of 13 patients receiving the artificial rib implants show no significant loss of pulmonary function based on spirometry tests. Based on our findings, the combined simulations and clinical results validate the strong mechanical performance and biocompatibility of the carbon fiber artificial ribs for chest wall reconstruction under static and dynamic loading while maintaining normal respiratory function.

Abstract This study aimed to develop a risk prediction model for gastrointestinal bleeding in patients after coronary artery bypass grafting (CABG) and assessed its accuracy. A retrospective analysis was conducted on 232 patients who underwent CABG under general anesthesia in our hospital between January 2022 and December 2022. The patients were divided into gastrointestinal bleeding (GIB) group (n = 52) and group without gastrointestinal bleeding (non-GIB) (n = 180). The independent risk factors for gastrointestinal bleeding in post-CABG patients were analyzed using χ2 test, t test and logistic multivariate regression analysis. A prediction model was established based on the identified risk factors. To verify the accuracy of the prediction model, a verification group of 161 patients who met the criteria was selected between January to June 2023, and the Bootstrap method was used for internal validation. The discrimination of the prediction model was evaluated using the area under the curve (AUC), where a higher AUC indicates a stronger discrimination effect of the model. The study developed a risk prediction model for gastrointestinal bleeding after CABG surgery. The model identified four independent risk factors: duration of stay in the intensive care unit (ICU) (OR 0.761), cardiopulmonary bypass time (OR 1.019), prolonged aortic occlusion time (OR 0.981) and re-operation for bleeding (OR 0.180). Based on these factors, an individualized risk prediction model was constructed. The C-index values of the modeling group and the verification group were 0.805 [95% CI (0.7303–0.8793)] and 0.785 [95% CI (0.6932–0.8766)], respectively, which indicated a good accuracy and discrimination of this model. The calibration and standard curves showed similar results, which further supported the accuracy of the risk prediction model. In conclusion, ICU time, cardiopulmonary bypass time, aortic occlusion time and re-operation for bleeding are identified as independent risk factors for gastrointestinal bleeding in patients after CABG. The risk prediction model developed in this study demonstrates strong predictive performance and provides valuable insights for clinical medical professionals in evaluating gastrointestinal complications in CABG patients.

Objective To validate the performance of a nucleic acid testing(NAT) system for blood screening in the high-altitude Nagqu region of Tibet, in order to assess the capability of NAT in high-altitude areas and further enhance blood safety. Methods Various methods were employed to evaluate the analytical sensitivity, reproducibility, ability to prevent cross-contamination, and comparison between different NAT systems. Results The NAT system in the Nagqu region of Tibet achieved a 100% detection rate for high-concentration HBV DNA and HIV-1 RNA samples, and over 90% for medium-concentration samples. PROBIT analysis revealed the lower limits of detection (LOD) for HBV DNA and HIV-1 RNA to be 8.29 IU/mL (95% CI, 5.88~20.55 IU/mL) and 40.52 IU/mL (95% CI, 30.26~85.92 IU/mL), respectively. For HCV RNA genotype 2a, the LOD was 97.14 IU/mL (95% CI, 71.00~182.67 IU/mL), all of which were lower than the declared minimum detectable concentrations in the instructions. Reproducibility analysis demonstrated a 100% level of consistency within the system. Cross-contamination performance verification showed a strong ability to resist cross-contamination. Comparative analysis of repeated testing of low-concentration HBV DNA samples and multi-system testing in plain areas revealed consistency rates of 77.78%(14/18) and 77.27%(17/22), respectively, indicating certain differences between the NAT system in Nagqu region and other systems. Conclusion The NAT system exhibited excellent performance in blood screening at high altitudes. The results of performance validation in high-altitude blood screening NAT systems were largely consistent with those in plain areas, providing a reliable basis for enhancing blood safety in high-altitude regions.

ObjectiveTo investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population.MethodsA total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk.ResultsThere were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01).ConclusionsIGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

Background: Arnicolide C, which is isolated from Centipeda minima, has excellent antitumor effects. However, the potential impacts and related mechanisms of action of arnicolide C in breast cancer remain unknown. Methods: The viability of breast cancer cells was measured using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony formation assays. For analysis of apoptosis and the cell cycle, flow cytometry was used. A molecular docking approach was used to explore the possible targets of arnicolide C. Western blot analysis was used to detect changes in the expression of 14-3-3θ and proteins in related pathways after arnicolide C treatment in breast cancer cells. The anti-breast cancer effect of arnicolide C in vivo was evaluated by establishing cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Results: Arnicolide C inhibited proliferation, increased apoptosis, and induced G1 arrest. In particular, molecular docking analysis indicated that arnicolide C binds to 14-3-3θ. Arnicolide C reduced 14-3-3θ expression and inhibited its downstream signaling pathways linked to cell proliferation. Similar results were obtained in the CDX and PDX models. Conclusion: Arnicolide C can have an anti-breast cancer effect both in vitro and in vivo and can induce cell cycle arrest and increase apoptosis in vitro. The molecular mechanism may be related to the effect of arnicolide C on the expression level of 14-3-3θ. However, the specific mechanism through which arnicolide C affects 14-3-3θ protein expression still needs to be determined.

We report a case of murine typhus in China caused by Rickettsia typhi and diagnosed by nanopore targeted sequencing of a bronchoalveolar lavage fluid sample. This case highlights that nanopore targeted sequencing can effectively detect clinically unexplained infections and be especially useful for detecting infections in patients without typical signs and symptoms.

Objectives Perianal infection is a serious complication in patients undergoing chemotherapy for haematological malignancies. Therefore, we aimed to develop a predictive model to help medical staff promptly screen patients at a high risk of perianal infection during chemotherapy.Design This was a single-centre prospective observational study.Setting This study was conducted in a tertiary teaching hospital in Chengdu, China.Participants The study sample comprised 850 patients with haematological malignancies who underwent chemotherapy at the department of haematology or our hospital between January 2021 and June 2022.Interventions The included patients were randomly divided into training and validation groups in a 7:3 ratio. Based on the discharge diagnosis, patients with perianal infection were selected as the case group and the other patients were selected as the control group.Outcome measure The main outcome measure was the occurrence of perianal infections.Results A predictive model for perianal infections was established. A history of perianal infection, haemorrhoids, constipation and duration of diarrhoea were independent risk factors. The area under the curve of the The area under the receiver operating characteristic (ROC) curve for the training and validation groups were 0.784 (95% CI 0.727 to 0.841) and 0.789 (95% CI 0.818 to 0.885), respectively. Additionally, the model had good calibration in both the training and validation groups with a non-significant Hosmer-Lemeshow test (p=0.999 and 0.482, respectively).Conclusions The risk prediction model, including a history of perianal infection, history of haemorrhoids, constipation and duration of diarrhoea ≥3 days of perianal infection in patients with haematological malignancies during chemotherapy, has good prediction reliability and can be helpful in guiding clinical medical staff in screening and early intervention of high-risk groups.

Li et al. evaluate the immunogenicity and safety of the CoronaVac inactivated COVID-19 vaccine in elderly patients with underlying medical conditions in China. Most patients show comparable neutralizing antibody and SARS-CoV-2-specific T cell responses to healthy controls, and no serious adverse effects are seen.

To evaluate the clinical efficacy of pelvic floor low-frequency electrical stimulation combined with anus lifting training in the treatment of urinary incontinence after radical prostatectomy in a Chinese cohort. Fifty-five patients with urinary incontinence after radical prostatectomy were randomly divided into treatment group and control group. Patients in control group received only anus lifting training therapy, while treatment group combined with pelvic floor low-frequency electrical stimulation. The urinary control including urinary incontinence questionnaire (ICI-Q-SF), urinary incontinence quality of life (I-QOL), visual analogue scale (VAS), and pelvic floor muscle strength assessment (Glazer) of the two groups of patients before treatment and every week was recorded for statistical analysis. There was a statistically significant difference between treatment group and control group in the urinary control curve. The scores of ICI-Q-SF, I-QOL, VAS, and Glazer in the treatment group after 2 weeks were statistically different from those before treatment, and effects were accumulating with the extension of treatment time. Compared with the control group, the scores of treatment group in the 2 to 10 weeks improved more significantly. Especially, in the sixth week, total effective rate of treatment group was significantly better than that of control group (74.07% [20/27], 35.71% [10/28], p < .05). The difference between two groups gradually narrowed after 10 weeks and no significant difference after 10 weeks of treatment between two groups. Pelvic floor low-frequency electrical stimulation combined with anus lifting training after radical prostatectomy can significantly shorten the recovery time of urinary incontinence in patients after radical prostatectomy.

Objectives Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events.Design A systematic review and meta-analysis.Data sources PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023.Eligibility criteria for studies We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking.Data extraction and synthesis Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method.Results 22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies.Conclusions This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.

Infective endocarditis (IE) is a rare but severe disease with high morbidity and mortality. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk of organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia–reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber (CytoSorbents Europe GmbH, Berlin, Germany) has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients undergoing cardiac surgery with cardiopulmonary bypass. However, there is currently no systematic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence, and future perspectives for CytoSorb® hemoadsorption therapy in IE patients.

Abstract Background Acute lung injury (ALI) caused by intestinal ischemia–reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia–reperfusion conditions. Methods To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). Results C-176 administration significantly attenuated intestinal ischemia–reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNβ mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. Conclusion C-176, a selective STING inhibitor, improves intestinal ischemia–reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.

Abstract Graphene patterning via etching is important for enhancing or controling the properties of devices and supporting their applications in micro- and nano-electronic fields. Herein, we present a simple, low-cost, and scalable wet etching method for graphene patterning. The technique uses hypochlorite solution combined with ultraviolet light irradiation to rapidly remove unwanted graphene areas from the substrate. Raman spectroscopy, atomic force microscopy, scanning electron microscopy, and optical microscopy results showed that well-patterned graphene with micrometer scale regions was successfully prepared. Furthermore, graphene field effect transistor arrays were fabricated, and the obtained devices exhibited good current–voltage characteristics, with maximum mobility of ~ 1600 cm2/Vs, confirming the feasibility of the developed technique.

Colorectal cancer (CRC) is a common cancer among both men and women and is one of the leading causes of cancer death worldwide. It is important to identify risk factors that may be used to help reduce morbidity and mortality of the disease. We used a case-control study design to explore the association between CRC, polygenic risk scores (PRS), and other factors. We extracted data about 2,585 CRC cases and 9,362 controls from the UK Biobank, calculated the PRS for these cases and controls based on 140 single nucleotide polymorphisms, and performed logistic regression analyses for the 11,947 cases and controls, for an older group (ages 50+), and for a younger group (younger than 50). Five significant risk factors were identified when all 11,947 cases and controls were considered. These factors were, in descending order of the values of the adjusted odds ratios (aOR), high PRS (aOR: 2.70, CI: 2.27-3.19), male sex (aOR: 1.52, CI: 1.39-1.66), unemployment (aOR: 1.47, CI: 1.17-1.85), family history of CRC (aOR: 1.44, CI: 1.28-1.62), and age (aOR: 1.01, CI: 1.01-1.02). These five risk factors also remained significant in the older group. For the younger group, only high PRS (aOR: 2.87, CI: 1.65-5.00) and family history of CRC (aOR: 1.73, CI: 1.12-2.67) were significant risk factors. These findings indicate that genetic risk for the disease is a significant risk factor for CRC even after adjusting for family history. Additional studies are needed to examine this association using larger samples and different population groups.

Background. Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods. The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results. Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions. Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Abstract While enzymatic hydrolysis is an effective method for lowering the antigenicity of cow milk (CM), research regarding the antigenicity and nutritional traits of CM hydrolysate is limited. Here, we evaluated the protein content, amino acid composition, sensory traits, color, flow behavior, and antigenicity of CM following enzymatic hydrolysis. The results showed that enzymatic hydrolysis increased the degree of hydrolysis, destroyed allergenic proteins, including casein, β-lactoglobulin, and ɑ-lactalbumin, and significantly increased the content of free amino acids and nutritional quality. In particular, the antigenicity of CM was significantly reduced from 44.05 to 86.55% (P

Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum–associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER– tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.

Abstract Background Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai. Method Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed. Results After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation. Conclusions In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Abstract An X-band reflectarray antenna using 16 × 12 double square ring elements for satellite communications is proposed in this paper. The feed is a 4 × 3 elements microstrip patch array designed to create edge taper of approximately − 10 dB. A prototype with right-hand circular polarization (RHCP) is manufactured and tested, and the good agreements between simulations and measurements are demonstrated. The good performance is obtained with the aperture efficiency of 40.7% and the 3-dB gain bandwidth of about 10% which is beneficial to nanosatellites.

Abstract Background Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumor progression by transferring exosomes to adjacent cells. Our aim was to clarify the role of LINC00659 encapsulated in CAFs-derived exosomes (CAFs-exo) in colorectal cancer (CRC). Methods CAFs and normal fibroblasts (NFs) were isolated and cultured. CAFs-exo and NFs-derived exosomes (NFs-exo) were characterized by transmission electron microscope and Western blot. The mRNA level of LINC00659 in CAFs-exo and NFs-exo were measured. Then we analyzed cell proliferation by CCK-8 and clone formation assay, cell migration by cell scratch, and cell invasion by Transwell. Epithelial mesenchymal transformation (EMT) related markers E-cadherin, N-cadherin, Vimentin and Snail-1 expressions were assessed by Western blot. The binding of LINC00659 and miR-342-3p, miR-342-3p and ANXA2 were analyzed by dual-luciferase reporter gene assay. Results CAFs and NFs showed a spindle-like morphology. CAFs-exo promoted CRC cell proliferation, migration, invasion and EMT progression. The expression of LINC00659 in CAF-derived exosomes was significantly increased, and fibroblasts could transfer exosomal LINC00659 to CRC cells. We further revealed that transfection of miR-342-3p mimic or sh-ANXA2 could obviously reverse the promotion effect of exosomal LINC00659 on CRC progression. Functional studies reveal that LINC00659 is transferred from CAFs to the cancer cells via exosomes, where it promotes CRC cell proliferation, invasion, migration and EMT progression in vitro. Mechanistically, LINC00659 interacts directly with miR-342-3p to increase ANXA2 expression in CRC cells. Conclusion Collected evidence supported that CAFs-derived exosomal LINC00659 promotes CRC cell proliferation, invasion and migration via miR-342-3p/ANXA2axis.

Abstract. Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

Abstract. Background. Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. Methods. Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. Results. A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak

Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25–62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high “rate of out-of-range tests” of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high “rate of out-of-range tests” or high LR+ may aid the AHI identification and missed diagnosis reduction.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

Background: Breast cancers can be divided into HER2-negative and HER2-positive subtypes according to different status of HER2 gene. Despite extensive studies connecting germline mutations with possible risk of HER2-negative breast cancer, the main category of breast cancer, it remains challenging to obtain accurate risk assessment and to understand the potential underlying mechanisms. Methods: We developed a novel framework named Damage Assessment of Genomic Mutations (DAGM), which projects rare coding mutations and gene expressions into Activity Profiles of Signalling Pathways (APSPs). Findings: We characterized and validated DAGM framework at multiple levels. Based on an input of germline rare coding mutations, we obtained the corresponding APSP spectrum to calculate the APSP risk score, which was capable of distinguish HER2-negative from HER2-positive cases. These findings were validated using breast cancer data from TCGA (AUC = 0.7). DAGM revealed that HER2 signalling pathway was up-regulated in germline of HER2-negative patients, and those with high APSP risk scores had exhibited immune suppression. These findings were validated using RNA sequencing, phosphoproteome analysis, and CyTOF. Moreover, using germline mutations, DAGM could evaluate the risk for HER2-negative breast cancer, not only in women carrying BRCA1/2 mutations, but also in those without known disease-associated mutations. Interpretation: The DAGM can facilitate the screening of subjects at high risk of HER2-negative breast cancer for primary prevention. This study also provides new insights into the potential mechanisms of developing HER2-negative breast cancer. The DAGM has the potential to be applied in the prevention, diagnosis, and treatment of HER2-negative breast cancer. Funding: This work was supported by the National Key Research and Development Program of China (grant no. 2018YFC0910406 and 2018AAA0103302 to CZ); the National Natural Science Foundation of China (grant no. 81202076 and 82072939 to MY, 81871513 to KW); the Guangzhou Science and Technology Program key projects (grant no. 2014J2200007 to MY, 202002030236 to KW); the National Key R&D Program of China (grant no. 2017YFC1309100 to CL); Shenzhen Science and Technology Planning Project (grant no. JCYJ20170817095211560 574 to YN); and the Natural Science Foundation of Guangdong Province (grant no. 2017A030313882 to KW and S2013010012048 to MY); Hefei National Laboratory for Physical Sciences at the Microscale (grant no. KF2020009 to GN); and RGC General Research Fund (grant no. 17114519 to YQS).

Phosphorus (P) participates in various assimilatory and metabolic processes in plants. Agricultural systems are facing P deficiency in many areas worldwide, while global P demand is increasing. Pioneering efforts have made us better understand the more complete use of residual P in soils and the link connecting plant P resorption to soil P deficiency, which will help to address the challenging issue of P deficiency. We summarized the state of soil “residual P” and the mechanisms of utilizing this P pool, the possible effects of planting and tillage patterns, various fertilization management practices and phosphate-solubilizing microorganisms on the release of soil residual P and the link connecting leaf P resorption to soil P deficiency and the regulatory mechanisms of leaf P resorption. The utilization of soil residual P represents a great challenge and a good chance to manage P well in agricultural systems. In production practices, the combination of “optimal fertilization and agronomic measures” can be adopted to utilize residual P in soils. Some agricultural practices, such as reduced or no tillage, crop rotation, stubble retention and utilization of biofertilizers-phosphate-solubilizing microorganisms should greatly improve the conversion of various P forms in the soil due to changes in the balance of individual nutrients in the soil or due to improvements in the phosphatase profile and activity in the soil. Leaf P resorption makes the plant less dependent on soil P availability, which can promote the use efficiency of plant P and enhance the adaptability to P-deficient environments. This idea provides new options for helping to ameliorate the global P dilemma.

Background Global warming can alter plant productivity, and community composition which has consequences for soil-plant associated microorganisms. Arbuscular mycorrhizal fungi (AMF) are distributed widely and form symbiotic relationships with more than 80% of vascular plants and play a key role in nutrient cycling processes at the ecosystem scale. Methods A simulated warming experiment at multiple elevations (3,000, 3,500, 3,800, and 4,170 m) was conducted utilizing an in-situ open-top chamber (OTC) for exploring the effect of global warming on AMF community structure in the Qinghai-Tibet Plateau (QTP). This region has been identified as one of the most sensitive areas to climatic changes. Soil DNA was extracted and sequenced using next the Mi-Seq platform for diversity profiling. Results AMF richness was higher under the simulated warming chamber, however this only occurred in the elevation of 3,500 m. Warming did not alter other AMF alpha diversity indices (e.g. Shannon, Ace, and Simpson evenness index). Glomus and Acaulospora were the dominate AMF genera as assessed through their relative abundance and occurrence in control and warming treatments at the different elevations. Conclusion Warming changed significantly AMF community. The effects of warming on AMF community structure varied depend on elevations. Moreover, the occurrences of AMF in different genera were also presented the different responses to warming in four elevations.

Background: Accumulating evidence has revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in various cancers. However, the biological function and regulation of m6A in bladder cancer (BC) are not yet fully understood. Methods: We performed cell phenotype analysis and established in vivo mouse xenograft models to assess the effects of m6A-modified ITGA6 on BC growth and progression. Methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation and luciferase reporter and mutagenesis assays were used to define the mechanism of m6A-modified ITGA6. Immunohistochemical analysis was performed to assess the correlation between METTL3 and ITGA6 expression in bladder cancer patients. Findings: We show that the m6A writer METTL3 and eraser ALKBH5 altered cell adhesion by regulating ITGA6 expression in bladder cancer cells. Moreover, upregulation of ITGA6 is correlated with the increase in METTL3 expression in human BC tissues, and higher expression of ITGA6 in patients indicates a lower survival rate. Mechanistically, m6A is highly enriched within the ITGA6 transcripts, and increased m6A methylations of the ITGA6 mRNA 3’UTR promotes the translation of ITGA6 mRNA via binding of the m6A readers YTHDF1 and YTHDF3. Inhibition of ITGA6 results in decreased growth and progression of bladder cancer cells in vitro and in vivo. Furthermore, overexpression of ITGA6 in METTL3-depleted cells partially restores the BC adhesion, migration and invasion phenotypes. Interpretation: Our results demonstrate an oncogenic role of m6A-modified ITGA6 and show its regulatory mechanisms in BC development and progression, thus identifying a potential therapeutic target for BC. Fund: This work was supported by National Natural Science Foundation of China (81772699, 81472999). Keywords: N6-methyladenosine, ITGA6, METTL3, Progression, Bladder cancer

Abstract. Background:. The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. Methods:. The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. Results:. The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ 2 = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ 2 = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ 2 = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ 2 = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. Conclusions:. The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.

Many animal and plant pathogenic bacteria employ a type three secretion system (T3SS) to deliver type three effector proteins (T3Es) into host cells. Efficient secretion of many T3Es in the plant pathogen Xanthomonas campestris pv. campestris (Xcc) relies on the global chaperone HpaB. However, how the domain of HpaB itself affects effector translocation/secretion is poorly understood. Here, we used genetic and biochemical approaches to identify a novel domain at the C-terminal end of HpaB (amino acid residues 137-160) that contributes to virulence and hypersensitive response (HR). Both in vitro secretion assay and in planta translocation assay showed that the secretion and translocation of T3E proteins depend on the C-terminal region of HpaB. Deletion of the C-terminal region of HpaB did not affect binding to T3Es, self-association or interaction with T3SS components. However, the deletion of C-terminal region sharply reduced the mounts of free T3Es liberated from the complex of HpaB with the T3Es, a reaction catalyzed in an ATP-dependent manner by the T3SS-associated ATPase HrcN. Our findings demonstrate the C-terminal domain of HpaB contributes to disassembly of chaperone-effector complex and reveal a potential molecular mechanism underpinning the involvement of HpaB in secretion of T3Es in Xcc.

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15-24 years and 25-34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803-0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989-0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.

Abstract Cataract surgery can cause macular thickness change. We used optical coherence tomography (OCT) to assess the macular thickness of different regions after femtosecond laser–assisted cataract surgery of age-related cataracts (ARC) and myopia cases with cataract (myopia group). Fifty eyes of 50 patients in ARC group and fifty eyes of 50 patients in myopia with cataract group were included. All study underwent femtosecond laser–assisted cataract surgery and macular thickness of was measured at pre-operation and 1 week, 1 month after surgery. There are significant differences of foveal thickness (P = 0.02), foveal volume (P = 0.02) and average retinal thickness (P = 0.02) between two groups before operation. In the myopia group, statistically significant differences were not found in postoperative macular thickness as compared with ARC group. There are differences in macular thickness between pre-operation and 1 month after operation when compared with nasal outer macular ring thickness (P = 0.022), foveal volume (P = 0.005) and average retinal thickness (P = 0.012) in ARC group. The study suggest that femtosecond laser–assisted cataract extraction is safe in myopia group that did not cause significant increase of macular thickness. However, an increased post-operative local macular thickness was recoded while comparing macular thickness with the baseline in ARC group.

Background: Mechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch. Methods: This randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bone marrow mononuclear cell (MNC) or placebo injections intradermally. Follow-up examinations were at 4, 8 weeks and 2 years. The primary endpoint was the volume achieved in relation to the designed size of the expander (expansion index, EI). Secondary endpoints were surface area, thickness and texture of expanded skin. This trial is registered with ClinicalTrial.gov, NCT01209611. Findings: The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, the MNC group had significantly thicker skin (epidermis: p

Background Inclusion of forage into the orchard is of great help in promoting the use efficiency of resources, while shading from trees restricts forage growth and production in the Loess Plateau of China. This study was aimed to investigate how tree shading affected leaf trait, photosynthetic gas exchange and chlorophyll feature of forages under the tree in the orchard-forage system. Methods The shading treatments were set as partially cutting branches (reduced shading), normal fruit tree shading (normal shading) and normal tree shading plus sun-shading net (enhanced shading) in an apple orchard. Leaf trait, photosynthesis, chlorophyll component and fluorescence related parameters were measured with lucerne (Medicago sativa), white clover (Trifolium repens) and cocksfoot (Dactylis glomerata) which were sown under apple trees. Results Shading imposed significant impacts on the growth and leaf photosynthetic characteristics, while there were differences among species. Enhanced shading decreased leaf thickness, leaf dry matter content (LDMC) and leaf mass per unit area (LMA). Biomass accumulation decreased with enhanced shading in cocksfoot, but did not change in white clover and lucerne which had much lower biomass accumulation than cocksfoot. Enhanced shading reduced net photosynthetic rate (Pn) of white clover and lucerne, but rarely affected cocksfoot, while it decreased instantaneous water use efficiency (WUEi) of cocksfoot but had few effects on the other forages. Enhanced shading reduced leaf dark respiration rate (Rd), light compensation point (LCP) and maximum assimilation rate. The Rd and LCP of cocksfoot were much lower than those of white clover and lucerne. Chlorophyll contents and chlorophyll a/b changed little with shading. Cocksfoot had the highest contents but lowest ratio. Maximum photochemical rate of photosystem II increased and non-photochemical quenching decreased with enhanced shading in cocksfoot, while did not change in the other forages. Discussion Leaf trait, photosynthetic gas exchange and chlorophyll feature were variously affected by species, shading and their interaction. Cocksfoot was more efficient than the other two forages in use of weakened light and more tolerant to tree shading. In the apple orchard, we recommend that reducing the density of apple tree or partially cutting branches together with selecting some shading-tolerant forages, i.e., cocksfoot, would be a practical option for the orchard-forage system in the Loess Plateau of China.

The deep-sea chemosynthetic environment is one of the most extreme environments on the Earth, with low oxygen, high hydrostatic pressure and high levels of toxic substances. Species of the family Vesicomyidae are among the dominant chemosymbiotic bivalves found in this harsh habitat. Mitochondria play a vital role in oxygen usage and energy metabolism; thus, they may be under selection during the adaptive evolution of deep-sea vesicomyids. In this study, the mitochondrial genome (mitogenome) of the vesicomyid bivalve Calyptogena marissinica was sequenced with Illumina sequencing. The mitogenome of C. marissinica is 17,374 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA genes (rrnS and rrnL) and 22 transfer RNA genes. All of these genes are encoded on the heavy strand. Some special elements, such as tandem repeat sequences, "G(A)nT" motifs and AT-rich sequences, were observed in the control region of the C. marissinica mitogenome, which is involved in the regulation of replication and transcription of the mitogenome and may be helpful in adjusting the mitochondrial energy metabolism of organisms to adapt to the deep-sea chemosynthetic environment. The gene arrangement of protein-coding genes was identical to that of other sequenced vesicomyids. Phylogenetic analyses clustered C. marissinica with previously reported vesicomyid bivalves with high support values. Positive selection analysis revealed evidence of adaptive change in the mitogenome of Vesicomyidae. Ten potentially important adaptive residues were identified, which were located in cox1, cox3, cob, nad2, nad4 and nad5. Overall, this study sheds light on the mitogenomic adaptation of vesicomyid bivalves that inhabit the deep-sea chemosynthetic environment.

BACKGROUND:China has the highest global prevalence of cigarette smokers, accounting for more than 40% of the total cigarette consumption in the world. Considering the shortage of smoking cessation services in China, and the acceptability, feasibility, and efficacy of mobile-phone-based text messaging interventions for quitting smoking in other countries, we conducted a mobile-phone-based smoking cessation study in China. METHODS AND FINDINGS:We conducted a randomized controlled trial in China across 30 cities and provinces from August 17, 2016, to May 27, 2017. Adult smokers aged 18 years and older with the intention to quit smoking were recruited and randomized to a 12-week high-frequency messaging (HFM) or low-frequency messaging (LFM) intervention ("Happy Quit") or to a control group in a 5:2:3 ratio. The control group received only text messages unrelated to quitting. The primary outcome was biochemically verified continuous smoking abstinence at 24 weeks. Secondary outcomes included (1) self-reported 7-day point prevalence of abstinence (i.e., not even a puff of smoke, for the last 7 days) at 1, 4, 8, 12, 16, 20, and 24 weeks; (2) self-reported continuous abstinence at 4, 12, and 24 weeks; and (3) self-reported average number of cigarettes smoked per day. A total of 1,369 participants received 12 weeks of intervention or control text messages with continued follow-up for 12 weeks. The baseline characteristics of participants among the HFM (n = 674), LFM (n = 284), and control (n = 411) groups were similar. The study sample included 1,295 (94.6%) men; participants had a mean age of 38.1 (SD 9.79) years and smoked an average of 20.1 (SD 9.19) cigarettes per day. We included the participants in an intention-to-treat analysis. Biochemically verified continuous smoking abstinence at 24 weeks occurred in 44/674 participants in the HFM group (6.5%), 17/284 participants in the LFM group (6.0%), and 8/411 participants (1.9%) in the control group; participants in both the HFM (odds ratio [OR] = 3.51, 95% CI 1.64-7.55, p < 0.001) and the LFM (OR = 3.21, 95% CI 1.36-7.54], p = 0.002) intervention groups were more likely to quit smoking than those in the control group. However, there was no difference in quit rate between the HFM and LFM interventions. We also found that the 7-day point quit rate from week 1 to week 24 ranged from approximately 10% to more than 26% with the intervention and from less than 4% to nearly 12% without the intervention. Those who continued as smokers in the HFM group smoked 1 to 3 fewer cigarettes per day than those in the LFM group over the 24 weeks of trial. Among study limitations, the participants were able to use other smoking cessation services (although very few participants reported using them), cotinine tests can only detect smoking status for a few days, and the proportion of quitters was small. CONCLUSIONS:Our findings demonstrate that a mobile-phone-based text messaging intervention (Happy Quit), with either high- or low-frequency messaging, led to smoking cessation in the present study, albeit in a low proportion of smokers, and can therefore be considered for use in large-scale intervention efforts in China. Mobile-phone-based interventions could be paired with other smoking cessation services for treatment-seeking smokers in China. TRIAL REGISTRATION:ClinicalTrials.gov NCT02693626.

The Kuroshio Current intrudes in the bottom layer of the East China Sea continental shelf from the northeast of Taiwan via two bottom branches named the Nearshore Kuroshio Branch Current (NKBC, along the 60 m isobath) and the Offshore Kuroshio Branch Current (OKBC, along the 100 m isobath). However, knowledge on the macrofaunal responses to these bottom branches is limited. This study examined the variations in the benthic macrofaunal community in a section of the East China Sea under the influence of the NKBC. Seven sites corresponding to three regions (the west, middle and east region) were sampled using an Agassiz trawl net at a monthly rate from February to November 2015 (except in August). A total of 270 macrofaunal species were collected in this study. Cluster analysis and nMDS ordination revealed three communities: the inshore, Kuroshio and offshore communities, roughly corresponding to the west, middle and east of NKBC route. Significant differences in the species composition (one-way PERMANOVA) and diversity indices (one-way ANOVA) among the regions and communities were observed, while no statistically significant difference among the months was detected. The indicator species also varied among the communities, with Sternaspis scutata and Odontamblyopus rubicundus dominating the inshore community, Camatopsis rubida, Schizaster lacunosus and Craspidaster hesperus dominating the Kuroshio community, and Portunus argentatus, Champsodon snyderi and Coelorinchus multispinulosus dominating the offshore community. Some rare species (e.g., Neobythites sivicola) may indicate the passage of the NKBC better than the indicator species. A redundancy analysis was used to describe the relationship between the macrofaunal species and environmental variables in this study. Water depth and turbidity played important roles in the distribution of the macrofauna. S. scutata and O. rubicundus were associated with high turbidity and shallow depth, while Plesionika izumiae and P. argentatus were associated with low turbidity and deep depth. This study outlines the impact of the NKBC on the distribution patterns of the macrofaunal community of the East China Sea. More studies are needed to understand the detailed interactions between macrofauna and the NKBC in the future.

Age-related cataract (ARC) is a leading cause of visual impairment and blindness worldwide. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC. Aside from increasing age, the risk factors for ARC appear to be rather complex, and one or more gene variations could play critical roles in the diverse processes of ARC progression. This study aimed to investigate the combined effects of different genetic variants on ARC risk.A cohort of 789 ARC patients and 531 normal controls from the Jiangsu Eye Study was included in this study. Genotyping of 18 single-nucleotide polymorphisms (SNPs) in 4 DNA damage/repair genes was performed using TaqMan SNP assays. SNP-SNP interactions were analyzed via multifactor dimensionality reduction (MDR), classification and regression tree (CART) and genetic risk score (GRS) analyses.Based on single-locus analyses of the 18 SNPs examined, WRN-rs11574311 (T>C) was associated with ARC risk. However, in MDR, the gene-gene interaction among the five SNPs (WRN-rs4733220 (G>A), WRN-rs1801195 (T>G), OGG1-rs2072668 (G>C) and OGG1-rs2304277 (A>G)) on ARC risk was significant (OR = 5.03, 95% CI: 3.54~7.13). CART analyses also revealed that the combination of five SNPs above was the best polymorphic signature for discriminating between the cases and the controls. The overall odds ratio for CART ranged from 4.56 to 7.90 showing an incremental risk for ARC. This result indicated that these critical SNPs participate in complex interactions. The GRS results showed an increased risk for ARC among individuals with the SNPs in this polymorphic signature.The use of multifactorial analysis (or an integrated approach) rather than a single methodology could be an improved strategy for identifying complex gene interactions. The multifactorial approach used in this study has the potential to identify complex biological relationships among ARC-related genes and processes. This approach will lead to the discovery of novel biological information, ultimately improving ARC risk management.

Amelogenesis imperfecta is a group of disorders causing abnormalities in enamel formation in various phenotypes. Many mutations in the FAM83H gene have been identified to result in autosomal dominant hypocalcified amelogenesis imperfecta in different populations. However, the structure and function of FAM83H and its pathological mechanism have yet to be further explored. Evolutionary analysis is an alternative for revealing residues or motifs that are important for protein function. In the present study, we chose 50 vertebrate species in public databases representative of approximately 230 million years of evolution, including 1 amphibian, 2 fishes, 7 sauropsidas and 40 mammals, and we performed evolutionary analysis on the FAM83H protein. By sequence alignment, conserved residues and motifs were indicated, and the loss of important residues and motifs of five special species (Malayan pangolin, platypus, minke whale, nine-banded armadillo and aardvark) was discovered. A phylogenetic time tree showed the FAM83H divergent process. Positive selection sites in the C-terminus suggested that the C-terminus of FAM83H played certain adaptive roles during evolution. The results confirmed some important motifs reported in previous findings and identified some new highly conserved residues and motifs that need further investigation. The results suggest that the C-terminus of FAM83H contain key conserved regions critical to enamel formation and calcification.

Disintegration in thalamocortical integration suggests its role in the mechanistic 'switch' from recreational to dysregulated drug seeking/addiction. In this study, we aimed to address whether thalamic nuclear groups show altered functional connectivity within the cerebral cortex in chronic ketamine users. One hundred and thirty subjects (41 ketamine users and 89 control subjects) underwent rsfMRI (resting-state functional Magnetic Resonance Imaging). Based on partial correlation functional connectivity analysis we partitioned the thalamus into six nuclear groups that correspond well with human histology. Then, in the area of each nuclear group, the functional connectivity differences between the chronic ketamine user group and normal control group were investigated. We found that the ketamine user group showed significantly less connectivity between the thalamic nuclear groups and the cortical regions-of-interest, including the prefrontal cortex, the motor cortex /supplementary motor area, and the posterior parietal cortex. However, no increased thalamic connectivity was observed for these regions as compared with controls. This study provides the first evidence of abnormal thalamocortical connectivity of resting state brain activity in chronic ketamine users. Further understanding of pathophysiological mechanisms of the thalamus in addiction (ketamine addiction) may facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of this complex disease.