Bifunctional Interphase with Target-Distributed Desolvation Sites and Directionally Depositional Ion Flux for Sustainable Zinc Anode.

Aqueous zinc batteries (AZBs) feature high safety and low cost, but intricate anodic side reactions and dendrite growth severely restrict their commercialization. Herein, ethylenediaminetetraacetic acid (EDTA) grafted metal organic framework (MOF-E) is proposed as a dually-functional anodic interphase for sustainable Zn anode. Specifically, the target-distributed EDTA serves as an ion-trapped tentacle to accelerate the desolvation and ionic transport by powerful chemical coordination, while the MOFs offer suitable ionic channels to induce oriented deposition. As a result, MOF-E interphase fundamentally suppresses side reactions and guides horizontally arranged Zn deposition with (002) preferred orientations. The Zn|MOF-E@Cu cell exhibits a markedly improved Coulombic efficiency of 99.7 % over 2500 cycles, and the MOF-E@Zn|KVOH (KV12 O30-y ⋅ nH2 O) cell yields a steady circulation of 5000 cycles@90.47 % at 8 A g-1 .

CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most lethal tumour worldwide. Copine 1 (CPNE1) was identified as a novel oncogene in NSCLC in our previous study. However, its specific function and relative mechanisms remain poorly understood. METHODS: The biological role of CPNE1 and RACK1 in NSCLC was investigated using gene expression knockdown and overexpression, cell proliferation assays, clonogenic assays, and Transwell assays. The expression levels of CPNE1, RACK1 and other proteins were determined by western blot analysis. The relationship between CPNE1 and RACK1 was predicted and investigated by mass spectrometry analysis, immunofluorescence staining, and coimmunoprecipitation. NSCLC cells were treated with a combination of a MET inhibitor and gefitinib in vitro and in vivo. RESULTS: We found that CPNE1 facilitates tumorigenesis in NSCLC by interacting with RACK1, which further induces activation of MET signaling. CPNE1 overexpression promoted cell proliferation, migration, invasion and MET signaling in NSCLC cells, whereas CPNE1 knockdown produced the opposite effects. In addition, the suppression of the enhancing effect of CPNE1 overexpression on tumorigenesis and MET signaling by knockdown of RACK1 was verified. Moreover, compared to single-agent treatment, dual blockade of MET and EGFR resulted in enhanced reductions in the tumour volume and downstream signaling in vivo. CONCLUSIONS: Our findings show that CPNE1 promotes tumorigenesis by interacting with RACK1 and activating MET signaling. The combination of a MET inhibitor with an EGFR-TKI attenuated tumour growth more significantly than either single-drug treatment. These findings may provide new insights into the biological function of CPNE1 and the development of novel therapeutic strategies for NSCLC. Video Abstract.

Cryptic Sulfur and Oxygen Cycling Potentially Reduces N2O-Driven Greenhouse Warming: Underlying Revision Need of the Nitrogen Cycle.

Increasing global deoxygenation has widely formed oxygen-limited biotopes, altering the metabolic pathways of numerous microbes and causing a large greenhouse effect of nitrous oxide (N2O). Although there are many sources of N2O, denitrification is the sole sink that removes N2O from the biosphere, and the low-level oxygen in waters has been classically thought to be the key factor regulating N2O emissions from incomplete denitrification. However, through microcosm incubations with sandy sediment, we demonstrate here for the first time that the stress from oxygenated environments does not suppress, but rather boosts the complete denitrification process when the sulfur cycle is actively ongoing. This study highlights the potential of reducing N2O-driven greenhouse warming and fills a gap in pre-cognitions on the nitrogen cycle, which may impact our current understanding of greenhouse gas sinks. Combining molecular techniques and kinetic verification, we reveal that dominant inhibitions in oxygen-limited environments can interestingly undergo triple detoxification by cryptic sulfur and oxygen cycling, which may extensively occur in nature but have been long neglected by researchers. Furthermore, reviewing the present data and observations from natural and artificial ecosystems leads to the necessary revision needs of the global nitrogen cycle.

A high environmental composite quality factor score was associated with the risk of sick building syndrome among adults in northeast China.

OBJECTIVES: Epidemiological evidence regarding the association between the combination of indoor and outdoor neighborhood pollution and sick building syndrome (SBS) among adults is limited and inconsistent. A cross-sectional study was conducted to investigate the association between the environmental composite quality factor score and SBS among adults. METHODS: This study included 2594 females and 666 males aged 18-77 years enrolled from the Northeast China. The environmental composite quality factor score was computed based on factors potentially associated with SBS risk, including the outdoor neighborhood pollution sources (the housing on the street, the presence of pollutants within 100 m of the house (gutters, garbage stations, noise, chemical pollution, and dust pollution), and the presence of arterial roads, factories, and chimneys) and indoor pollution sources (redecoration, clean fuel used for heating/cooking, cooking oil fume (COF) outside kitchen, using of mosquito coil or repellent, and using of incense). We performed multivariate logistic regression analysis to calculate the odds ratios (ORs) and 95% confidence intervals (95%CIs) between environmental composite quality factor score, indoor pollution composite factor score, outdoor neighborhood pollution composite factor score, and SBS adjustment for covariates. Further, we also did the stratified analysis and constructed a weighted score to verify the results. RESULTS: Compared with the lowest environmental composite quality factor score, the ORs of the highest scores were: 1.58 (95% CI, 1.20-2.27, Ptrend = 0.001) for general symptoms; 1.73 (95% CI, 1.35-2.23, Ptrend < 0.001) for mucosal symptoms and 1.75 (95% CI, 1.34-2.29, Ptrend < 0.001) for dermal symptoms and 1.81 (95% CI, 1.36-2.42, Ptrend < 0.001) for all of the three symptoms. We also observed similar patterns with the using of weighted scores and stratified analysis. CONCLUSION: Higher exposure to indoor pollution sources and outdoor pollution sources near the residence may be associated with a higher risk of SBS in adults in northeast China.

Active case finding with case management: the key to tackling the COVID-19 pandemic.

COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2.

Family Structure, Family Instability, and Child Psychological Well-Being in the Context of Migration: Evidence From Sequence Analysis in China.

This study conceptualizes parental migration as a dynamic family process that exposes children to parental absence and family instability. Using detailed migration histories, this study identifies the left-behind trajectories of rural Chinese children throughout childhood (age 1-12) and examines the impact on psychological well-being (N = 3,961). Results indicate heterogeneity in children's experience of parental migration, which is characterized by both persistence (prolonged parental absence) and instability (repeated parental migration). A quarter of rural children experienced prolonged parental migration, and for half of these, by both parents. Another 50% of rural children experienced repeated parental migration. Children continuously left behind by both parents and children who experienced substantial family instability both fared worse in psychological development than those in stable two-parent families.

UBC Mediated by SEPT6 Inhibited the Progression of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets. METHODS: The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer. RESULTS: UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth. CONCLUSION: In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer.

Economic Implications of Chinese Diagnosis-Related Group-Based Payment Systems for Critically Ill Patients in ICUs.

OBJECTIVES: To evaluate the economic implications of payments based on Chinese diagnosis-related groups for critically ill patients in ICUs in terms of total hospital expenditure, out-of-pocket payments, and length of stay. DESIGN: A pre-post comparison of patient cohorts admitted to ICUs 1 year before and 1 year after Chinese diagnosis-related group reform was undertaken. Demographic characteristics, clinical data, and medical expenditures were collated from a health insurance database. SETTING: Twenty-two public hospitals in Sanming, Southern China. PATIENTS: All patients admitted to ICUs from January 1, 2017, to December 31, 2018. INTERVENTION: The implementation of Chinese diagnosis-related group-based payments on January 1, 2018. MEASUREMENTS AND MAIN RESULTS: Economic variables (total expenditures, out-of-pocket payments, and length of stay) were calculated for each patient from the day of hospital admission to the day of hospital discharge. Adjusted mean out-of-pocket payment estimates were 29.46% (p < 0.001) lower following reform. Adjusted mean out-of-pocket payments fell by 41.32% for patients in neonatal ICU, whereas there were no significant decreases in out-of-pocket payments for patients in PICU and adult ICU. Furthermore, adjusted mean out-of-pocket payments decreased by 55.74% in secondary hospitals, but there was no significant change in tertiary hospitals after Chinese diagnosis-related group reform. No significant changes were found in total expenditures and length of stay. CONCLUSIONS: Chinese diagnosis-related group policy provided an opportunity for critically ill patients in ICUs to achieve at least short-term financial benefits in reducing out-of-pocket payments, without affecting the total expenditures and length of stay. Chinese diagnosis-related group-based payment significantly relieved financial burdens for patients with lower illness severities, such as patients in neonatal ICU. The results of this study can offer significant insights for policymakers in reducing the financial burden on critically ill patients, both in China and in other countries with similar systems.

The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy.

Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (ß2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express ß2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.

Early post-operative serum albumin level predicts survival after curative nephrectomy for kidney cancer: a retrospective study.

BACKGROUND: Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer. METHODS: We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed. RESULTS: A total of 329 patients were included. The median duration of follow-up was 54.8 months. Patients with an early post-operative serum albumin level < 32 g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5 months, P = 0.001) and median overall survival (OS; 52.2 versus 57.0 months, P = 0.049) than patients with an early post-operative serum albumin level ≥ 32 g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level < 32 g/L was an independent prognostic factor associated with a decreased RFS (HR = 3.60; 95% CI,1.05-12.42 [months], P = 0.042) and decreased OS (HR = 9.95; 95% CI, 1.81-54.80 [months], P = 0.008). CONCLUSION: An early post-operative serum albumin level < 32 g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.

Significance of MRI/Transrectal Ultrasound Fusion Three-Dimensional Model-Guided, Targeted Biopsy Based on Transrectal Ultrasound-Guided Systematic Biopsy in Prostate Cancer Detection: A Systematic Review and Meta-Analysis.

PURPOSE: To assess MRI/Transrectal Ultrasound (TRUS) fusion three-dimensional model-guided targeted biopsy (3D-Tb) versus TRUS-guided systematic biopsy (Sb) in detecting overall and high-Gleason-score (≥7) prostate cancer (PCa). METHODS: Pubmed and Web of science were searched. Studies with men having a suspicious lesion on MRI were included, which were divided into initial biopsy, previous negative biopsy, and mixed groups in meta-analysis. RESULTS: Totally 13 cohorts in 12 studies, with 3,225 men were included. In total population, 3D-Tb and Sb did not differ significantly in the PCa detection rate (43.1 vs. 42.6%, p = 0.36), but after excluding initial biopsy group, the superiority of 3D-Tb became significant (p = 0.01); 3D-Tb had a significantly higher detection rate of high-Gleason-score PCa compared to Sb (30.0 vs. 24.1%, p < 0.05); 3D-Tb plus Sb significantly improved the PCa detection rate based on Sb alone (52.7 vs. 42.6%, p < 0.05). CONCLUSIONS: In men with increased serum PSA and/or abnormal DRE and suspicious lesion on MRI but non-previous evidence of PCa, 3D-Tb plus Sb improves the PCa detection rate based on Sb alone. 3D-Tb alone has better performance in detecting high-Gleason-score PCa, and tends to have a higher PCa detection rate in population with previous negative biopsy compared to Sb.

Short-term efficacy and safety of low-intensity extracorporeal shock wave therapy in erectile dysfunction: a systematic review and meta-analysis.

AIM: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients. MATERIALS AND METHODS: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1month after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment. RESULTS: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95% confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n=101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n=121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported. CONCLUSION: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and long-term follow-up time studies are needed to confirm our analysis.

Combination therapy only shows short-term superiority over monotherapy on ureteral stent-related symptoms - outcome from a randomized controlled trial.

BACKGROUND: Controversy remains on the superiority of combination therapy over monotherapy on ureteral stent-related symptoms (SRSs). We tend to explore if there is a necessity of combination therapy. METHODS: One hundred cases of unilateral upper urinary tract calculi with stent insertion (pre and post flexible ureteroscopy) were randomized into 4 groups, given non-treatment, solifenacin, tamsulosin or combination respectively. Eight times of follow-ups were given after each insertion. RESULTS: SRSs released spontaneously within 4 days after insertion (p = 0.017) but then stay with no further improvement. Benefit of solifenacin on flank pain started showing after day4 (p = 0.002), which was comparable to that of tamsulosin and combination (p = 0.914 vs 0.195). Combination therapy showed superiority over both monotherapy before day4, but after then solifenacin and tamsulosin showed similar effectiveness with the combination therapy on both bladder pain (p = 0.229 vs 0.394) and urgency (p = 0.813 vs 0.974). No improvement on hematuria or frequency was observed in each group. CONCLUSIONS: Combination therapy takes effect faster but shows no supervisory after the first few days compared with monotherapy. TRIAL REGISTRATION: The study protocol was registered on Chinese Clinical Trial Register on April 17th, 2013 (registration number: ChiCTR-TRC-13003148 ).

Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk.

BACKGROUND: Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high-density lipoprotein that can play important roles in tumor invasion and metastasis. The objective of the present study was to evaluate the association of two genetic variants (-75 G/A and +83 C/T) of APOA1 with predisposition to renal cancer. METHODS: A total of 432 subjects, including 216 pathologically-proven renal cancer cases and 216 age- and gender-matched healthy controls, were recruited into this hospital-based case-control study. Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: Patients with renal cancer had a significantly higher frequency of APOA1 -75 AA genotype [odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.18, 3.75; P = 0.01] and APOA1 -75 A allele (OR =1.40, 95% CI = 1.05, 1.87; P = 0.02) than controls. When stratifying by the distant metastasis status, patients with distant metastasis had a significantly higher frequency of APOA1 -75 AA genotype genotype (OR =2.20, 95% CI = 1.04, 4.68; P = 0.04). CONCLUSION: This study is, to our knowledge, the first to examine prospectively an increased risk role of APOA1 -75 AA genotype and APOA1 -75 A allele in renal cancer susceptibility.

Case report: Systemic presentation of ALK-positive Histiocytosis.

ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.

When does a freemium business model lead to high performance? - A qualitative comparative analysis based on fuzzy Sets.

Existing research has neglected to explain why freemium business models lead to differentiated performance or what accounts for the difference in their revenue models. This study investigates how the configuration effect of freemium business models promotes performance and explores the different ways through which freemium business models, their dynamic capabilities, and environmental uncertainty interact to achieve high performance. The fuzzy set qualitative comparative analysis (fsQCA) approach was used to test the conceptual model with data from 45 freemium business model apps. From empirical evidence on the relationship between freemium business models, dynamic capabilities, and environmental uncertainty, the study finds that (1) bundled and fragmented freemium business models are fundamental performance drivers. However, they work only in combination with dynamic capabilities and environmental uncertainty. Moreover, the bundled and fragmented freemium business models have complementary rather than substitution relationships. (2) For companies with bundled and fragmented freemium business models, high sensing and seizing capabilities are critical to achieving high performance. A high bundled freemium business model, high sensing capability, and a lack of fragmented freemium business models and seizing capability can lead to high performance, regardless of reconfiguration capabilities and environmental uncertainty. (3) Under high environmental uncertainty, offering fragmented freemium business models with or without a bundled freemium business model will lead to high performance if they have high sensing, seizing, and reconfiguring capabilities. This study can provide systematic decision support for achieving high performance through freemium business models and the configuration of dynamic capabilities under environmental uncertainty.