A Synergistically Regulated Cathode/Electrolyte Interphase With High Stability and Rapid Zn2+ Migration Toward Advanced Flexible Zinc-Ion Batteries.

Na3V2(PO4)3(NVP), as a representative sodium superionic conductor with a stable polyanion framework, is considered a cathode candidate for aqueous zinc-ion batteries attributed to their high discharge platform and open 3D structure. Nevertheless, the structural stability of NVP and the cathode-electrolyte interphase (CEI) layer formed on NVP can be deteriorated by the aqueous electrolyte to a certain extent, which will result in slow Zn2+ migration. To solve these problems, doping Si elements to NVP and adding sodium acetate (NaAc) to the electrolyte are utilized as a synergistic regulation route to enable a highly stable  CEI with rapid Zn2+ migration. In this regard, Ac- competitively takes part in the solvation structure of Zn2+ in aqueous electrolyte, weakening the interaction between water and Zn2+, and meanwhile a highly stable CEI is formed to avoid structural damage and enable rapid Zn2+ migration. The NVPS/C@rGO electrode exhibits a notable capacity of 115.5 mAh g-1 at a current density of 50 mA g-1 in the mixed electrolyte (3 M ZnOTF2+3 M NaAc). Eventually, a collapsible "sandwich" soft pack battery is designed and fabricated and can be used to power small fans and LEDs, which proves the practical application of aqueous zinc-ion batteries in flexible batteries.

Associations between prenatal exposure to per- and polyfluoroalkyl substances and plasma immune molecules in three-year-old children in China.

BACKGROUND: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children. METHODS: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression. RESULTS: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (ß = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (ß = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA). CONCLUSIONS: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development.

Electroencephalography Monitoring for Preventing Postoperative Delirium and Postoperative Cognitive Decline in Patients Undergoing Cardiothoracic Surgery: A Meta-Analysis.

Background: Patients undergoing cardiothoracic surgery frequently encounter perioperative neurocognitive disorders (PND), which can include postoperative delirium (POD) and postoperative cognitive decline (POCD). Currently, there is not enough evidence to support the use of electroencephalograms (EEGs) in preventing POD and POCD among cardiothoracic surgery patients. This meta-analysis examined the importance of EEG monitoring in POD and POCD. Methods: Cochrane Library, PubMed, and EMBASE databases were searched to obtain the relevant literature. This analysis identified trials based on the inclusion and exclusion criteria. The Cochrane tool was used to evaluate the methodological quality of the included studies. Review Manager software (version 5.3) was applied to analyze the data. Results: Four randomized controlled trials (RCTs) were included in this meta-analysis, with 1096 participants. Our results found no correlation between EEG monitoring and lower POD risk (relative risk (RR): 0.81; 95% CI: 0.55-1.18; p = 0.270). There was also no statistically significant difference between the EEG group and the control group in the red cell transfusions (RR: 0.86; 95% CI: 0.51-1.46; p = 0.590), intensive care unit (ICU) stay (mean deviation (MD): -0.46; 95% CI: -1.53-0.62; p = 0.410), hospital stay (MD: -0.27; 95% CI: -2.00-1.47; p = 0.760), and mortality (RR: 0.33; 95% CI: 0.03-3.59; p = 0.360). Only one trial reported an incidence of POCD, meaning we did not conduct data analysis on POCD risk. Conclusions: This meta-analysis did not find evidence supporting EEG monitoring as a potential method to reduce POD incidence in cardiothoracic surgery patients. In the future, more high-quality RCTs with larger sample sizes are needed to validate the relationship between EEG monitoring and POD/POCD further.

Management of Chronic Heart Failure in Dialysis Patients: A Challenging but Rewarding Path.

Chronic heart failure (CHF) is a common complication and cause of death in dialysis patients. Although several clinical guidelines and expert consensus on heart failure (HF) in the general population have been issued in China and abroad, due to abnormal renal function or even no residual renal function (RRF) in dialysis patients, the high number of chronic complications, as well as the specificity, variability, and limitations of hemodialysis (HD) and peritoneal dialysis (PD) treatments, there are significant differences between dialysis patients and the general population in terms of the treatment and management of HF. The current studies are not relevant to all dialysis-combined HF populations, and there is an urgent need for high-quality studies on managing HF in dialysis patients to guide and standardize treatment. After reviewing the existing guidelines and literature, we focused on the staging and diagnosis of HF, management of risk factors, pharmacotherapy, and dialysis treatment in patients on dialysis. Based on evidence-based medicine and clinical trial data, this report reflects new perspectives and future trends in the diagnosis and treatment of HF in dialysis patients, which will further enhance the clinicians' understanding of HF in dialysis patients.

Evaluation of the analytical and clinical performance of a new high-sensitivity cardiac troponin I assay: hs-cTnI (CLIA) assay.

OBJECTIVES: Cardiac troponin (cTn) is the key biomarker for diagnosis of acute coronary syndrome (ACS). We performed a complete assessment of the high-sensitivity cardiac troponin I (hs-cTnI) (CLIA) assay on the analytical performance and clinical diagnostic performance, which was compared with Abbott ARCHITECT hs-cTnI assay. METHODS: Sex-specific 99th percentile upper reference limits (URLs) were determined from a healthy population of 424 males and 408 females. High-sensitivity performance was assessed by examining the imprecision at sex-specific URLs and the detectable results above LoD in a cohort of healthy population. The diagnostic performance of the hs-cTnI (CLIA) assay was validated in a population of 934 patients with suspected ACS. RESULTS: The 99th percentile URLs were 15.3 ng/L for female, 31.3 ng/L for male and 24.2 ng/L for overall population. The total imprecision near the sex-specific 99th percentile URLs were <5 %. 76.74 % of females, 97.12 % of males and 86.69 % of overall population had cTnI values exceeding the LoD, which met the criteria of high-sensitivity troponin assay. No cross-reactivity or interference was identified. The diagnostic sensitivity, specificity, PPV, NPV, and AUC of hs-cTnI (CLIA) assay were 97.97 , 90.70, 79.02, 99.21 % and 0.9885, respectively, which were comparable to ARCHITECT hs-cTnI assay. CONCLUSIONS: hs-cTnI (CLIA) assay is a high-sensitivity troponin I method with high precision, sensitivity and specificity. The clinical diagnostic performance of hs-cTnI (CLIA) is comparable to the established ARCHITECT hs-cTnI assay. Mindray's hs-cTnI (CLIA) assay is an attractive alternative for diagnosis of myocardial infarction with a high level of accuracy and safety.

Future embracing: exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy.

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and is associated with high rates of end-stage renal disease. Early detection and precise interventions are crucial for improving patient prognosis and quality of life. However, the current diagnosis primarily relies on renal biopsies and traditional biomarkers, which have limitations. Additionally, targeted therapeutic strategies are lacking. Exosomes, small vesicles that facilitate intercellular communication, have emerged as potential noninvasive diagnostic markers due to their stability, diverse cargo, and rapid detectability. They also hold promise as carriers for gene and drug delivery, presenting innovative opportunities in renal disease prognosis and treatment. However, research on exosomes in the context of idiopathic membranous nephropathy (IMN) remains limited, with a focus on exploring urinary exosomes as IMN markers. In this review, we summarize the current status of MN diagnosis and treatment, highlight the fundamental characteristics of exosomes, and discuss recent advancements in their application to IMN diagnosis and therapy. We provide insights into the clinical prospects of exosomes in IMN and acknowledge potential challenges. This article aims to offer forward-looking insights into the future of exosome-mediated IMN diagnosis and treatment, indicating a revolutionary transformation in this field.

Enhance PD/A biofilm formation via a novel biochar/tourmaline modified-biocarriers to treat low-strength contaminated surface water: Initial adhesion and high-substrate microenvironment.

In this work, a novel polyurethane carrier modified with biochar and tourmaline/zeolite powder at ratio of 1:1 and 1:2 was developed to promote the formation of biofilms and the synergy of overall bacterial activity for Partial Denitrification/Anammox to treat low-nitrogen contaminated surface water. Based on the batch experiment, the modified biocarrier, BTP2 (biochar: tourmaline = 2: 1), exhibited the highest total nitrogen removal efficiency (83.63%) under influent total nitrogen of 15 mg/L and COD/NO3- of 3. The dense biofilm was formed in inner side of biocarrier owing to the increased surface roughness and various functional groups suggested by scanning electron microscopy and Fourier-transform infrared analysis. The EPS content increased from 200.15 to 220.26 mg/g VSS in BTP2 system. Besides, the rapid NH4+ capture and organics release of the modified carrier fueled the growth of anammox and denitrification bacteria, with the activity of 2.13 ± 0.52 mg N/gVSS/h and 6.70 ± 0.52 mg N/gVSS/h (BTP2). High-throughput sequencing unraveled the increased abundances of Candidatus_Competibacter (0.82%), Thauera (0.60%) and Candidatus_Brocadia (0.55%) which was responsible for the synergy of incomplete reduction of NO3- to NO2- and NH4+ oxidation. Overall, this study provided a valid and simple-control guide for biofilm formation towards rapid enrichment and great collaboration of Anammox and denitrification bacteria.

A Highly Stable and Non-Flammable Deep Eutectic Electrolyte for High-Performance Lithium Metal Batteries.

Deep eutectic electrolytes (DEEs) are regarded as one of the next-generation electrolytes to promote the development of lithium metal batteries (LMBs) due to their unparalleled advantages compared to both liquid electrolytes and solid electrolytes. However, its application in LMBs is limited by electrode interface compatibility. Here, we introduce a novel solid dimethylmalononitrile (DMMN)-based DEE induced by N coordination to dissociate LiTFSI. We confirmed that the DMMN molecule can promote the dissociation of LiTFSI by the interaction between the N atom and Li+, and form the hydrogen bond with TFSI- anion, which can promote the dissociation of LiTFSI to form DEE. More importantly, due to the absence of active α-hydrogen, DMMN exhibits greatly enhanced reduction stability with Li metal, resulting in favorable electrode/electrolyte interface compatibility. Polymer electrolytes based on this DEE exhibit high ionic conductivity (0.67 mS cm-1 at 25 ℃), high oxidation voltage (5.0 V vs. Li+/Li), favorable interfacial stability and nonflammability. Li‖LFP and Li‖NCM811 full batteries utilizing this DEE polymer electrolyte exhibit excellent long-term cycling stability and excellent rate performance at high rates. Therefore, the new DMMN-based DEE overcomes the limitations of traditional electrolytes in electrode interface compatibility and opens new possibilities for improving the performance of LMBs.

Age-specific transmission dynamics under suppression control measures during SARS-CoV-2 Omicron BA.2 epidemic.

BACKGROUND: From March to June 2022, an Omicron BA.2 epidemic occurred in Shanghai. We aimed to better understand the transmission dynamics and identify age-specific transmission characteristics for the epidemic. METHODS: Data on COVID-19 cases were collected from the Shanghai Municipal Health Commission during the period from 20th February to 1st June. The effective reproductive number (Rt) and transmission distance between cases were calculated. An age-structured SEIR model with social contact patterns was developed to reconstruct the transmission dynamics and evaluate age-specific transmission characteristics. Least square method was used to calibrate the model. Basic reproduction number (R0) was estimated with next generation matrix. RESULTS: R0 of Omicron variant was 7.9 (95% CI: 7.4 to 8.4). With strict interventions, Rt had dropped quickly from 3.6 (95% CI: 2.7 to 4.7) on 4th March to below 1 on 18th April. The mean transmission distance of the Omicron epidemic in Shanghai was 13.4 km (95% CI: 11.1 to 15.8 km), which was threefold longer compared with that of epidemic caused by the wild-type virus in Wuhan, China. The model estimated that there would have been a total 870,845 (95% CI: 815,400 to 926,289) cases for the epidemic from 20th February to 15th June, and 27.7% (95% CI: 24.4% to 30.9%) cases would have been unascertained. People aged 50-59 years had the highest transmission risk 0.216 (95% CI: 0.210 to 0.222), and the highest secondary attack rate (47.62%, 95% CI: 38.71% to 56.53%). CONCLUSIONS: The Omicron variant spread more quickly and widely than other variants and resulted in about one third cases unascertained for the recent outbreak in Shanghai. Prioritizing isolation and screening of people aged 40-59 might suppress the epidemic more effectively. Routine surveillance among people aged 40-59 years could also provide insight into the stage of the epidemic and the timely detection of new variants. TRIAL REGISTRATION: We did not involve clinical trial.

Object Detection Based on Lightweight YOLOX for Autonomous Driving.

Accurate and rapid response in complex driving scenarios is a challenging problem in autonomous driving. If a target is detected, the vehicle will not be able to react in time, resulting in fatal safety accidents. Therefore, the application of driver assistance systems requires a model that can accurately detect targets in complex scenes and respond quickly. In this paper, a lightweight feature extraction model, ShuffDet, is proposed to replace the CSPDark53 model used by YOLOX by improving the YOLOX algorithm. At the same time, an attention mechanism is introduced into the path aggregation feature pyramid network (PAFPN) to make the network focus more on important information in the network, thereby improving the accuracy of the model. This model, which combines two methods, is called ShuffYOLOX, and it can improve the accuracy of the model while keeping it lightweight. The performance of the ShuffYOLOX model on the KITTI dataset is tested in this paper, and the experimental results show that compared to the original network, the mean average precision (mAP) of the ShuffYOLOX model on the KITTI dataset reaches 92.20%. In addition, the number of parameters of the ShuffYOLOX model is reduced by 34.57%, the Gflops are reduced by 42.19%, and the FPS is increased by 65%. Therefore, the ShuffYOLOX model is very suitable for autonomous driving applications.

Efficient nitrogen removal from mature landfill leachate by single-stage partial-nitritation anammox using expanded granular sludge bed.

The effective retention of anaerobic ammonia oxidizing (anammox) bacteria and its high sensitivity to toxic substances and oxygen posed a major challenge to the application of partial nitrification combined with anammox (PN/A) in mature landfill leachate treatment, although it is a promising and efficient nitrogen removal process. In this study, a single-stage PN/A process based on expanded granular sludge bed was proposed to treat the mature landfill leachate. During the last phase, when the NH+ 4-N concentration of mature landfill leachate in influent was 1150.0 mg/L, the nitrogen removal efficiency (NRE) was 83.64% with 1.07 kg N/(m3·d) nitrogen removal rate (NRR). The activity of anammox bacteria (AnAOB) and ammonia oxidizing bacteria (AOB) was 9.21 ± 0.22 mg N/(gVSS·h) and 14.34 ± 0.65 mg N/(gVSS·h), respectively. The bacteria produced a high amount of tightly bound extracellular polymeric substance (TB-EPS) i.e., 4071.79 mg/(g·VSS). This helped to create granular sludge and provided favorable spatial conditions for the distribution of functional bacteria that were adapted to different environments. Due to the efficient retention of functional bacteria by the granular sludge, the relative abundance of Ca.Brocadia and Ca.Kuneneia was 1.71% and 0.31%, respectively. Redundancy analysis (RDA) and microbial correlation network diagram showed that the relative abundance of Ca. Kuenenia, Nitrosomonas and Truepera had a stronger positive correlation with the increase of the proportion of mature landfill leachate added to the influent. Overall, the PN/A process based on granular sludge provides an effective method for autotrophic biological nitrogen removal from mature landfill leachate.

Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method.

Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR (1H, 13C, and DEPT), and 2D-NMR (1H-1H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II.

[Characterization and identification of chemical components in traditional Chinese medicine Psoraleae Fructus based on UHPLC-Q-TOF-MS].

This study was designed to comprehensively characterize and identify the chemical components in traditional Chinese medicine Psoraleae Fructus by establishing an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) method in combination with in-house library. The chromatographic separation conditions(stationary phase, column temperature, mobile phase, and elution gradient) and key MS monitoring parameters(capillary voltage, nozzle voltage, and fragmentor) were sequentially optimized via single-factor experiments. A BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was finally adopted, with the mobile phase consisting of 0.1% formic acid in water(A) and acetonitrile(B) at the flow rate of 0.4 mL·min~(-1) and column temperature of 30 ℃. Auto MS/MS was utilized for data acquisition in both positive and negative ion modes. By comparison with reference compounds, analysis of the MS~2 fragments, in-house library retrieval and literature research, 83 compounds were identified or tentatively characterized from Psoraleae Fructus, including 58 flavonoids, 11 coumarins, 4 terpenoid phenols, and 10 others. Sixteen of them were identified by comparison with reference compounds, and ten compounds may have not been reported from Psoraleae Fructus. This study achieved a rapid qualitative analysis on the chemical components in Psoraleae Fructus, which provided useful reference for elucidating its material basis and promoting the quality control.

Quantitative assessment of the effects of massive nucleic acid testing in controlling a COVID-19 outbreak.

BACKGROUND: From 20 July to 26 August 2021, local outbreaks of COVID-19 occurred in Nanjing City and Yangzhou City (Jiangsu Province, China). We analyzed the characteristics of these outbreaks in an effort to develop specific and effective intervention strategies. METHODS: Publicly available data on the characteristics of the COVID-19 outbreaks in Jiangsu Province were collected. Logistic regression was used to assess the association of age and sex with clinical severity. Analysis of onset dates, generation time distributions, and locations were used to estimate the mean transmission distance. A branching process model was used to evaluate different management strategies. RESULTS: From 20 July to 26 August 2021, 820 patients were diagnosed with COVID-19 in Jiangsu Province, with 235 patients (28.7%) from Nanjing, 570 (69.5%) from Yangzhou, and 15 (1.8%) from other cities. Overall, 57.9% of the patients were female, 13.7% were under 20 years-old, and 58.3% had moderate disease status. The mean transmission distance was 4.12 km, and closed-loop management of the area within 2.23 km of cases seemed sufficient to control an outbreak. The model predicted that the cumulative cases in Yangzhou would increase from 311 to 642 if the interval between rounds of nucleic acid amplification testing (NAAT) increased from 1 to 6 days. It also predicted there would be 44.7% more patients if the NAAT started 10 days (rather than 0 days) after diagnosis of the first case. The proportion of cases detected by NAAT would increase from 11.16 to 44.12% when the rounds of NAAT increased from 1 to 7 within 17 days. When the effective vaccine coverage was 50%, the outbreak would be controlled even when using the most relaxed non-pharmaceutical interventions. CONCLUSIONS: The model predicted that a timely closed-loop management of a 2.23 km area around positive COVID-19 cases was sufficient to control the outbreak. Prompt serial NAAT is likely to contain an outbreak quickly, and our model results indicated that three rounds of NAAT sufficiently controlled local transmission. Trial registration We did not involve clinical trial.

Wastewater treatment and reuse situations and influential factors in major Asian countries.

As Asia is the most populous continent in the world, the contradiction between water supply and demand is increasing. Wastewater treatment and reclaimed water use are important means to solve the contradiction between supply and demand and realize the sustainability of the water management system. Based on the data collected from 48 typical countries and regions in Asia, this study evaluates the possible influential factors on wastewater treatment and reclaimed water use such as Gross Domestic Product (GDP) level, water resource availability, water withdrawn and water stress. It is identified that per capita GDP and water stress are important factors affecting wastewater treatment and reclaimed water use. Although reclaimed water use in most Asian countries is still at the early stage, the development of wastewater treatment is conducive to the development of reclaimed water. The results of this study are believed to be useful in improving water management and sustainability levels in Asian countries.

CXCR4-SF1 bifunctional adipose-derived stem cells benefit for the treatment of Leydig cell dysfunction-related diseases.

Stem cell transplantation is a candidate method for the treatment of Leydig cell dysfunction-related diseases. However, there are still many problems that limit its clinical application. Here, we report the establishment of CXCR4-SF1 bifunctional adipose-derived stem cells (CXCR4-SF1-ADSCs) and their reparative effect on Leydig cell dysfunction. CD29+ CD44+ CD34- CD45- ADSCs were isolated from adipose tissue and purified by fluorescence-activated cell sorting (FACS). Infection with lentiviruses carrying the CXCR4 and SF1 genes was applied to construct CXCR4-SF1-ADSCs. The CXCR4-SF1-ADSCs exhibited enhanced migration and had the ability to differentiate into Leydig-like cells in vitro. Furthermore, the bifunctional ADSCs were injected into BPA-mediated Leydig cell damage model mice via the tail vein. We found that the CXCR4-SF1-ADSCs were capable of homing to the injured testes, differentiating into Leydig-like cells and repairing the deficiency in reproductive function caused by Leydig cell dysfunction. Moreover, we investigated the mechanism underlying SF1-mediated differentiation and testosterone synthesis in Leydig cells, and the B-box and SPRY Domain Containing Protein (BSPRY) gene was proposed to be involved in this process. This study provides insight into the treatment of Leydig cell dysfunction-related diseases.

SIRT2 suppresses expression of inflammatory factors via Hsp90-glucocorticoid receptor signalling.

SIRT2 is a NAD+ -dependent deacetylase that deacetylates a diverse array of protein substrates and is involved in many cellular processes, including regulation of inflammation. However, its precise role in the inflammatory process has not completely been elucidated. Here, we identify heat-shock protein 90α (Hsp90α) as novel substrate of SIRT2. Functional investigation suggests that Hsp90 is deacetylated by SIRT2, such that overexpression and knock-down of SIRT2 altered the acetylation level of Hsp90. This subsequently resulted in disassociation of Hsp90 with glucocorticoid receptor (GR), and translocation of GR to the nucleus. This observation was further confirmed by glucocorticoid response element (GRE)-driven reporter assay. Nuclear translocation of GR induced by SIRT2 overexpression repressed the expression of inflammatory cytokines, which were even more prominent under lipopolysaccharide (LPS) stimulation. Conversely, SIRT2 knock-down resulted in the up-regulation of cytokine expression. Mutation analysis indicated that deacetylation of Hsp90 at K294 is critical for SIRT2-mediated regulation of cytokine expression. These data suggest that SIRT2 reduces the extent of LPS-induced inflammation by suppressing the expression of inflammatory factors via SIRT2-Hsp90-GR axis.

Germline mutation and aberrant transcripts of WWOX in a syndrome with multiple primary tumors.

Multiple primary tumors are defined by the presence of two or more independent primary tumors in the same or different organs of an individual patient. However, the underlying genetic cause for the development of multiple primary tumors is largely unknown. In the study, we report a rare case with four synchronous distinct histological cancer types in a 26 years old Chinese female. In the patient, whole-exome sequencing identified a homozygous germline insertion mutation in WWOX which encodes the DNA repair-related enzyme, WW domain containing oxidoreductase. The mutation was found in a heterozygous state in her parents and brother without any cancer phenotype thus far. Surprisingly, we found multiple novel aberrant WWOX transcripts in the patient's normal colon tissue. The patient's colon metastasis from clear cell adenocarcinoma of the ovary showed a nonhypermutated profile enriched for C-T transition, and harbored somatic pathogenic mutations of HRAS, BRCA2, SMAD4, CHEK2, and AKT1 genes. To our knowledge, this is the first study reporting WWOX gene aberrations in a young patient with the early occurrence of multiple primary tumors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Anomalous proton conduction behavior across a nanoporous two-dimensional conjugated aromatic polymer membrane.

We investigate aqueous proton penetration behavior across a newly synthesized nanoporous two-dimensional conjugated aromatic polymer (2D-CAP) membrane using extensive ReaxFF reactive molecular dynamics simulations. We found that the proton penetration energy barrier across 2D-CAP is twice as high as that of graphtetrayne, even though 2D-CAP exhibits a larger pore size. Detailed analysis indicates that the anomalous high proton conduction energy barrier of 2D-CAP originates from its unique atomic nanopore structure. The hydrogen atoms at the periphery of the 2D-CAP nanopores can form a stable local hydrogen bond network with water molecules inside or surrounding the nanopores. The mobility of water molecules involved in this local hydrogen bond network will be significantly lowered, and the proton transportation process across the nanopores will thus be impeded. Our results show that the proton penetration behavior across nanoporous 2D materials is influenced not only by the pore size, but also by the decorated atoms or functional groups at the pore edges. Hydrogen atoms at the periphery of nanopores with certain geometry can form a stable local hydrogen bond network with neighboring water molecules, further hampering the proton conductivity.

A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.