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The issues of energy shortage and environmental pollution have accelerated the electrification of construction machinery (CM) industry globally. In China, the amount of electric construction machinery (ECM) has been growing across the industry. The sales of ECM are estimated to reach 600 000 vehicles by the end of 2025, while the total demand for battery power will reach 60 GWh. However, the development of ECM still faces critical challenges including reliable power supply and energy distribution among various components. In this review, we primarily focus on important technological breakthroughs and the difficulties faced by the CM industry in China. An overview of ECM including classification and characteristics is given at the beginning. Next, the selection of key components such as the electric motor and the energy storage units, and the control strategy in the pure electric drive system are discussed. The characteristics of the hybrid electric drive system such as structure design and power matching are analyzed in detail. The battery management system (BMS) is critical to ensure appropriate battery health for reliable power supply. Here, we extensively review technical developments in various BMSs. In addition, we roughly estimate the national total of CM emissions and the potential environmental benefits of employing ECMs in China. Finally, we set out future research directions and industrial development of ECM.

Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein in the immunoglobulin superfamily expressed on the surface of multiple cell populations and upregulated by inflammatory stimuli. It mediates cellular adhesive interactions by binding to the β2 integrins macrophage antigen 1 and leukocyte function-associated antigen 1, as well as other ligands. It has important roles in the immune system, including in leukocyte adhesion to the endothelium and transendothelial migration, and at the immunological synapse formed between lymphocytes and antigen-presenting cells. ICAM-1 has also been implicated in the pathophysiology of diverse diseases from cardiovascular diseases to autoimmune disorders, certain infections, and cancer. In this review, we summarize the current understanding of the structure and regulation of the ICAM1 gene and the ICAM-1 protein. We discuss the roles of ICAM-1 in the normal immune system and a selection of diseases to highlight the breadth and often double-edged nature of its functions. Finally, we discuss current therapeutics and opportunities for advancements.

Introduction: Ureteric obstruction commonly presents as a urological emergency requiring urgent intervention with urinary diversion. Double J stenting (DJS) is the preferred option to relieve ureteric tract obstruction in our centre. Objective: Our study aims to determine the feasibility and outcomes of DJS by general surgeons and medical officers in a hospital without a resident urologist and to identify the possible predictive factors for successful DJS. Methods: This is a clinical audit of all patients scheduled for DJS in Hospital Bintulu, Sarawak, from January 2017 to March 2020. A total of 57 patients were included. Socio-demographic data and factors predicting success rate, i.e., level of ureteric obstruction and its causes (intrinsic or extrinsic), diagnosis, size and nature of stone(s), degree of hydronephrosis and pre-operative renal profile, were collected. Success rate and postoperative outcomes for all successful cases were evaluated. Bivariate statistical analyses were used to investigate the association of predictive factors with the success rate of DJS. Results: Double J stenting was successful in 63.2% (36 cases) of our total samples of 57 cases. Out of 36 successful cases, 82.1% of the cases were able to return to baseline renal profile within 14 days and 83.3% did not develop fever within 3 days post-operative. The post-operative mean length of stay was 3.16 days and post-operative day 1 mean pain score was 0.72. Causes of obstruction by intrinsic factors, urolithiasis, pre-operative normal serum creatinine (

High oil/water interfacial area together with accessible interfaces for regents is the key to achieving efficient asymmetric catalysis in water. Herein, by taking advantage of the excellent interfacial activity of Janus nanosheets (JNS), as well as the unique compatibility of imidazolium ionic liquid (IL), we developed a series of IL-functionalized amphiphilic Janus mesosilica nanosheets which afford highly accessible reaction interfaces for highly enantioselective sulfoxidation in water. The JNS-typed chiral salen TiIV catalysts were prepared by selectively decorating hydrophobic chiral salen TiIV complex on one side of Janus mesosilica nanosheets through the imidazolium-based IL linker. Benefiting from the two-dimensional porous Janus structure, as well as the compatible IL linker, the IL-tagged JNS catalysts afforded high oil/water interfacial areas and highly accessible reaction interface for sulfides and H2O2, significantly accelerating asymmetric sulfoxidation in water using H2O2 as an oxidant. In addition, they can be facilely recovered for stable reuse by simple centrifugation.

In this study, the feasibility of using ZrO2 coatings, fabricated through the atmospheric pressure plasma jet technique, as top coats in thermal barrier systems was explored. Inconel 617 was used as the substrate material, and sputtered laminated RuAl/RuAlZr/Ru was used as the bond coat. >20-μm-thick ZrO2 coatings were deposited through several iterations of deposition at 500 °C and annealing at 600 °C; here, ZrO2 existed in the tetragonal phase. The tetragonal ZrO2 was stable after annealing at up to 700 °C but transformed into a mixture of tetragonal and monoclinic ZrO2 phases when annealed at >800 °C. The thermal stability of the ZrO2/RuAl/RuAlZr/Ru/Inconel 617 assembly was evaluated at 800–900 °C in air. The variations in volumetric fractions of the tetragonal and monoclinic ZrO2 phases were recorded; 44% of the tetragonal phase remained after 100 h of annealing at 800 °C, whereas 80% of the tetragonal phase had transformed into the monoclinic phase after 4 h of annealing at 900 °C. Observation of BC after annealing at 800 °C indicated that a dense thermally grown oxide scale, comprising O and Al, formed between the ZrO2 and RuAl layers, which impeded the inward diffusion of O. The inhibition of O diffusion declined with the crystallization of the thermally grown oxide scale into the δ-Al2O3 phase when the annealing time was extended.

In this contribution, we developed a simple, scalable, and universal strategy to exfoliate conjugated porous polymers (CPPs) into 2D nanosheets. A series of pyrenyl (Py)-, benzene (B)-, thienyl (T)-, thieno[3,2-b]thiophene (Tt)- and dithieno[3,2-b:2′,3′-d]thiophene (Ttt)-based CPPs were facilely exfoliated into 2D ultrathin sheets with a thickness of 5–18 nm in reasonable yields of 6–20% upon sonication in N-methyl pyrrolidone. Owing to more exposed active sites and shorter migration distances of charge carriers, the photocatalytic hydrogen production rate of the CPP 2-D nanosheets is 1.5–20 times higher than those of their bulk counterparts. The current study represents the first systematic report on the solvent-assisted exfoliation of CPP materials to produce 2D ultrathin lamellae from bulk CPPs with common structures, which might provide new possibilities for the practical application of 2D CPPs.

In this work, Ni–Cu bimetallic alloy nanoparticles supported on reduced graphene oxide (Ni–Cu ANPs/RGO) was successfully fabricated through a one-step hydrothermal synthesis method, where simultaneous reduction of graphene oxide, nickel salt and copper salt was performed, and relevant characterization studies were executed. This synthetic method does not require surfactants and high temperature treatment, and is recommended as a green, convenient and effective way to produce composites. The unique two-dimensional architecture of the RGO provides a large specific surface area, contributing to loading more Ni–Cu ANPs, while the uniformly distributed Ni–Cu bimetallic alloy nanoparticles enhance the electrocatalytic performance of glucose oxidation. The non-enzymatic glucose biosensor based on Ni–Cu ANPs/RGO showed a wide linear range (from 0.01 μM to 30 μM), low detection limit (0.005 μM), and excellent sensitivity (1754.72 μA mM−1 cm−2). More importantly, the high reliability and the excellent selectivity in actual sample detection will broaden its practical application in electrochemical sensing.

Semiconductor heterojunctions benefiting from efficient charge transfer and separation have been widely used in photocatalysis. Herein, heterojunctions based on polymeric and inorganic semiconductors, namely PyOT@TiO2, have been successfully constructed via in situ C–H activation polycondensation of the pyrene unit (Py-) and 3-(2-(2-ethoxyethoxy)ethoxy)thiophene unit (-OT) in the presence of titanium dioxide (TiO2). The combination of the polymeric semiconductor PyOT with TiO2 not only broadens the light response of TiO2, but also dramatically promotes the photo-generation exciton separation of PyOT. As a result, the optimized 50% PyOT@TiO2 composite exhibited extensive visible light absorption (400–520 nm) and the highest photocatalytic hydrogen evolution rate using ascorbic acid (AA) as the sacrificial agent, which is approximately 135 and 21 times higher than those of single-components TiO2 and PyOT, respectively. Mechanistic study by XPS, M–S plots and hydroxyl radical detection tests revealed the p–n heterojunction characteristics of PyOT@TiO2 that contributed to the enhanced photocatalytic performance. Our work develops a promising strategy for the in situ construction of polymeric–inorganic soft–hard heterostructures via atom-economic C–H activation polymerization.

The impact of infrastructure investment on social-economic system or ecological system has been widely discussed, yet, the overall impact of infrastructure investment on social-ecological system (SES) is still unknown. This study summarized the impact mechanism of infrastructure investment on social ecosystem vulnerability. We first sorted out the impact mechanism of infrastructure investment on SES vulnerability, and then empirically analyzed the effect of provincial infrastructure investment on SES vulnerability by using spatial autocorrelation and spatial econometric models on the basis of accounting provincial per capita infrastructure capital stock and comprehensive evaluation of SES vulnerability. The results showed that the infrastructure capital stock per capita at provincial level increased significantly during 2004-2017, with a spatial pattern that the north was higher than the south and the east/west was higher than the middle in China. The provincial SES vulnerability was improved, with spatial distribution characteristics of gradually getting worse from east to west in China. There was positive spatial correlation between provincial infrastructure investment and SES vulnerability, with aggregation distribution characteristics. There was inverted U-shaped relationship between infrastructure investment and SES vulnerability in China, that was, the appropriate investment of infrastructure at early could decrease SES vulnerability, while over-investment would increase it. Our results revealed the overall impact mechanism and dynamic characteristics of infrastructure investment on SES vulnerability, and could provide theoretical and policy-making support for the coordination of infrastructure construction and SES vulnerability governance at the macro level for China.基础设施投入对社会经济或生态系统的影响已被广泛讨论,但对社会-生态系统(SES)的作用如何仍不得而知。本研究梳理了基础设施投入对SES脆弱性的影响机理,并在核算省域人均基础设施资本存量及综合评估SES脆弱性的基础上,采用空间自相关与空间计量模型实证分析了我国省域基础设施投入对SES脆弱性的作用。结果表明: 2004—2017年,我国省域人均基础设施投入水平显著提高,且呈北高南低、东西高中间低的空间分布格局;省域SES脆弱性也在不断改善,却表现出由东向西逐步恶化的分布特点;我国省域人均基础设施投入与SES脆弱性具有空间正相关性,存在聚集性分布特征;两者呈倒U型曲线关系,即早期适量基础设施投入会降低SES脆弱性,而过度投入则会导致SES脆弱性逐步增加。本研究揭示了基础设施投入对SES脆弱性的影响机理与动态特点,可为宏观层面统筹协调基础设施建设与SES脆弱性治理提供理论与决策支持。.

The MRE11-RAD50-NBS1 (MRN) complex plays a crucial role in DNA double-strand breaks (DSBs) sensing and initiation of signaling cascades. However, the precise mechanisms by which the recruitment of MRN complex is regulated has yet to be elucidated. Here, we identified TRIpartite motif-containing protein 24 (TRIM24), a protein considered as an oncogene overexpressed in cancers, as a novel signaling molecule in response to DSBs. TRIM24 is essential for DSBs-induced recruitment of MRN complex and activation of downstream signaling. In the absence of TRIM24, MRN mediated DSBs repair is remarkably diminished. Mechanistically, TRIM24 is phosphorylated by ataxia-telangiectasia mutated (ATM) and then recruited to DSBs sites, facilitating the accumulation of the MRN components to chromatin. Depletion of TRIM24 sensitizes human hepatocellular carcinoma cells to cancer therapy agent-induced apoptosis and retards the tumor growth in a subcutaneous xenograft tumor mouse model. Together, our data reveal a novel function of TRIM24 in response to DSBs through regulating the MRN complex, which suggests that TRIM24 may be a potential therapeutic molecular target for tumor treatment.

Increasing evidence has revealed the roles of long noncoding RNAs (lncRNAs) as tumor biomarkers. Here, we introduce an immune-associated nine-lncRNA signature for predicting distant metastasis in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The nine lncRNAs are identified through microarray profiling, followed by RT–qPCR validation and selection using a machine learning method in the training cohort (n = 177). This nine-lncRNA signature classifies patients into high and low risk groups, which have significantly different distant metastasis-free survival. Validations in the Guangzhou internal (n = 177) and Guilin external (n = 150) cohorts yield similar results, confirming that the signature is an independent risk factor for distant metastasis and outperforms anatomy-based metrics in identifying patients with high metastatic risk. Integrative analyses show that this nine-lncRNA signature correlates with immune activity and lymphocyte infiltration, which is validated by digital pathology. Our results suggest that the immune-associated nine-lncRNA signature can serve as a promising biomarker for metastasis prediction in LA-NPC.

Afatinib is the only currently approved EGFR-tyrosine kinase inhibitors for advanced non-small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I. However, there are limited real-world data concerning the benefits and resistance mechanisms of afatinib in patients with these nonclassical mutations. To fill this gap, the present study was conducted.All NSCLC patients treated with afatinib were screened, and patients with EGFR G719X/L861Q/S768I were enrolled into the analysis. Either tumor tissue or blood specimens were detected by the commercial next-generation sequencing (NGS) panels or amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) to figure out the mutation genotype.A total of 106 advanced NSCLC patients with EGFR G719X/L861Q/S768I received afatinib treatment. The benefits of afatinib exhibited heterogeneity in different mutation genotypes. Notably, at baseline, NGS testing was performed in 59 patients, and TP53 was the most frequently coexisting mutation. Patients with TP53 mutations obtained fewer survival benefits than those with TP53 wild-type. A total of 68 patients ultimately experienced progression, and 27 patients received NGS testing to clarify the potential resistance mechanisms. EGFR-T790M, CDK4 amplification, FGFR1 amplification, PIK3CA, MET amplification, RET fusions, HER2, and BRAF mutations were identified in three (11.1%), three (11.1%), three (11.1%), three (11.1%), three (11.1%), one (3.7%), one (3.7%), and one (3.7%) of the cases, respectively. Five patients underwent ARMS-PCR testing for detecting EGFR-T790M mutation, and only one patient was T790M-positive.The present study elucidated the differential benefits of afatinib within different mutation genotypes and first revealed the spectrum of potential resistance mechanisms in patients with EGFR G719X/L861Q/S768I. The results of this study may provide practical clinical information that can guide optimal treatment in this setting.

Background Reducing the energy cost of running with exoskeletons could improve enjoyment, reduce fatigue, and encourage participation among novice and ageing runners. Previously, tethered ankle exoskeleton emulators with offboard motors were used to greatly reduce the energy cost of running with powered ankle plantarflexion assistance. Through a process known as “human-in-the-loop optimization”, the timing and magnitude of assistance torque was optimized to maximally reduce metabolic cost. However, to achieve the maximum net benefit in energy cost outside of the laboratory environment, it is also necessary to consider the tradeoff between the magnitude of device assistance and the metabolic penalty of carrying a heavier, more powerful exoskeleton. Methods In this study, tethered ankle exoskeleton emulators were used to characterize the effect of peak assistance torque on metabolic cost during running. Three recreational runners participated in human-in-the-loop optimization at four fixed peak assistance torque levels to obtain their energetically optimal assistance timing parameters at each level. Results We found that the relationship between metabolic rate and peak assistance torque was nearly linear but with diminishing returns at higher torque magnitudes, which is well-approximated by an asymptotic exponential function. At the highest assistance torque magnitude of 0.8 Nm/kg, participants’ net metabolic rate was 24.8 ± 2.3% (p = 4e–6) lower than running in the unpowered devices. Optimized timing of peak assistance torque was as late as allowed during stance (80% of stance) and optimized timing of torque removal was at toe-off (100% of stance); similar assistance timing was preferred across participants and torque magnitudes. Conclusions These results allow exoskeleton designers to predict the energy cost savings for candidate devices with different assistance torque capabilities, thus informing the design of portable ankle exoskeletons that maximize net metabolic benefit.

Accurate breast lesion surface localization can guarantee accurate biopsy and local treatment. But there is no guideline to regular equipment and methods for the localization of breast lesions. The conventional non-invasive localization method is marker-based localization. The advantages of this method are simple and efficient. The disadvantages are that markers disappear easily under coupling agents; the positioning length of markers cannot last long on skin; and healthcare associated infection due to many patients using the same marker pen is potentially unavoidable. Breast lesion sticker (called sticker for short) is a new-type localization medical instrument in 2020. Our study aims to explore the clinical value of a new lesion stickers in breast lesion surface localization via comparison of the sticker and marker pen localization methods.This was a prospective cohort study. It was conducted in 67 patients who needed breast lesion surface localization before biopsy. The patients were randomly assigned into 2 groups. One group of patients used marker pen to mark breast lesion surface location by ultrasonography. The other group of patients used stickers. Patients labeled with markers on skin were swabbed agents before marking. Then the markers were checked by ultrasound scan. If the surface positions of breast lesion were not correct, the above procedure was repeated. In the sticker group, the stickers were released synchronously after the lesions were detected by ultrasound scan. Then locations were checked via scanning hole. If the surface positions of breast lesion were not correct, the above procedure was repeated. The accuracy of positioning, the length of positioning time and satisfaction of patients between the 2 groups were compared. The length of positioning time was calculated from the time when ultrasound detected the lesion to the time when the surface position of breast lesion was confirmed. The total score of patients' satisfaction was 5 points according to Service Quality Evaluation of SERVQUAL Scale, including sonographers' service attitude and their technical proficiency, other medical staffs' service attitude and their technical proficiency, hospital service procedures, positioning comfort, and positioning effects.All 67 patients were females, aged 18-66 (39.73±13.10). There were 35 patients in the marker pen group and 32 patients in the sticker group. The time length of group used marker pen to localization was 22-88 (52.20±2.90) s, and the sticker group was 3-15 (9.22±0.58) s in length. The length of positioning time for the stickers was significantly shorter than that of the marker (The new breast lesion positioning stickers have more advantages than the marker pen in localization efficiency. It could reduce the workload of medical workers and increase patients' satisfaction to some extent. The stickers can be used not only in the breast lesions surface localization, but also in the skin location of pleural effusion and ascites, the skin location of surface masses, the skin location of thyroid nodule, and many other clinical marker areas, to further expand the scope of clinical application and value of the stickers.

Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer’s disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aβ42 and Aβ40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aβ42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.

While direct bandgap monolayer 2D transition metal dichalcogenides (TMDs) have emerged as an important optoelectronic material due to strong light–matter interactions, their multilayer counterparts...

Sheng-Yan Huang,* Yang Chen,* Xi-Rong Tan, Sha Gong, Xiao-Jing Yang, Qing-Mei He, Shi-Wei He, Na Liu, Ying-Qing Li Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Na Liu; Ying-Qing LiSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of ChinaTel/Fax +86-20-87342370; +86-20-87343255 Email liun1@sysucc.org.cn; liyingq1@sysucc.org.cnPurpose: The prognostic value of serum calcium levels in nasopharyngeal carcinoma (NPC) remains unknown. This study aimed to evaluate the prognostic value of serum calcium levels in patients with NPC.Patients and Methods: A total of 2094 patients diagnosed with NPC between April 2009 and September 2012 were enrolled in this retrospective analysis. The median follow-up time was 96.3 months (range: 4.1– 120.0 months). Univariate and multivariable Cox proportional hazards models were used to identify significant and independent prognostic predictors of overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS).Results: Overall, low serum calcium levels were detected in 1109/2094 (53.00%) patients and tended to be more frequently detected in older (P< 0.001) and female (P=0.001) patients. Patients with low serum calcium levels had poorer OS (P=0.011), DFS (P=0.012) and DMFS (P=0.004) than those with high serum calcium levels, but serum calcium levels had no significant effect on RFS (P=0.376). In univariate and multivariable analyses, low serum calcium levels were a statistically significant and independent prognostic factor for OS, DFS, and DMFS but had no prognostic value for RFS.Conclusion: Serum calcium levels can serve as a prognostic predictor and guide more individualized treatment for NPC patients.Keywords: nasopharyngeal carcinoma, serum calcium level, prognosis, survival

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor ubiquitously associated with the Epstein‐Barr virus (EBV), which is highly prevalent in South China, Southeast Asia, and North Africa. Despite being a highly radio‐sensitive and treatable cancer, a majority of NPC patients are diagnosed in their advanced stage, and locoregional and distant relapses following definitive treatment contribute largely to cancer‐specific mortality among these patients. Given that EBV‐driven NPC is the predominant variant seen in endemic regions, various EBV detection methods have been developed and are utilized in screening, prognostication, and post‐treatment surveillance of NPC patients. While the Immunoglobulin A (IgA) serology assay is the most extensively studied EBV detection method, the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening, prognostication, and detection of distant relapse. Furthermore, there is emerging evidence on the use of circulating tumor cells, microRNAs, DNA hypermethylation, and combination assays in various clinical scenarios. Herein, this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC. Specifically, the recent advances, clinical evidence, and challenges associated with the clinical application of EBV liquid biopsies in population screening, prognostication, and surveillance of NPC are presented.

A simple, dual-modular aptasensor for accurate determination of cardiac troponin I (cTnI), a sensitive biomarker of acute myocardial infarction, is reported. It has the parallel output of electrochemiluminescence (ECL) and electrochemical impedance spectroscopy (EIS) based on target-gated transportation of signal probes (luminol/H2O2 or Fe(CN)63-/4-). The sensing capacity is originated from the amino-functionalized mouth margin of the nanochannels in a vertically oriented mesoporous silica film, which was in situ-grown on indium tin oxide-coated glass. With the linkage of glutaraldehyde to couple the aptamer as a trapper, it brings in the high specific target-gated response toward cTnI as decreased ECL or increased EIS. The concentration of cTnI is measurable by the ECL response within a wide linear range from 0.05 pg mL-1 to 10 ng mL-1, as well as the EIS response for a linear range between 0.05 pg mL-1 and 1 ng mL-1. Significantly, the self-verification of these two data from ECL and EIS validated each other with a satisfactory linear correlation (R2 = 0.999), thereby realizing the more reliable and accurate quantification to avoid false results. The designed strategy is an effective method for detection of cTnI, which is of great potential to apply in clinical detection.

This study describes a psychometric scale, the Inpatient Suicide Second Victim Experience and Support Tool, for evaluating physical and psychological distress with a focus on resources for supporting the needs of nursing professionals. Our study defines "second victim" as a nurse who experiences inpatient suicide while on shift. We conducted a cross-sectional study among non-psychiatric nurses to examine the psychometrics of the scale. A total of 731 participants were recruited from eight Chinese general hospitals for this research. Data were analyzed by exploratory factor analysis and confirmatory factor analysis to examine the reliability and validity of the scale. The results indicated adequate indices resulting in 21 items. The final structure for the scale was categorized into five domains: psychosomatic distress, support from family and friends, work-related support, organizational support, and professional self-efficacy. The total variance explained was 69.06%. Cronbach's alpha was 0.869 overall, and ranged from 0.626 to 0.914 for the five dimensions. The test-retest reliability of 0.792 for the entire scale was also acceptable. The scale shows promise for use by healthcare organizations to identify second victims and promote necessary organizational support interventions in Chinese hospitals.

It is traditionally believed that cerebral amyloid-beta (Aβ) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aβ. The role of peripherally produced Aβ in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aβ to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aβ in the blood, and caused AD phenotypes including Aβ plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aβ levels, and alleviated brain Aβ burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aβ plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aβ can decrease brain Aβ deposition and represents a novel therapeutic approach for AD.

Objective: The aims of the current study were to describe the serial CT characteristics of patients infected with COVID-19. In addition, in the light of the CT findings, we tried to determine whether virulence weakens during the transmission with quarantine management.Methods: Demographics, comorbidity, clinical findings, CT scanning, and scores of the affected lung parenchyma were compared for 131 patients with abnormality on CT images classified as COVID-19 pneumonia and the patients were divided between an imported group (n = 83) and indigenous group (n = 48), according to infected location. Two reviewers scored chest CT examinations for segmental involvement, ground glass opacities, consolidation, and honeycombing opacities. The 55 patients with peak CT "severity score" were selected o make a comparative analysis.Results: Patients’ demographics and comorbidities and clinical findings did not differ significantly between the two groups. The CT scores distribution trendline of the third CT scanning was lower than the former CT scanning. The peak CT scores trendline of the 55 selected COVID-19 patients in the indigenous group was lower than the imported group. The ROC analysis revealed an area under curve of 0.714 for the CT scanning with an optimal cutoff scores of 2.55 for prediction of contact history, a sensitivity of 76.3%, and a specificity of 52.9%.The peak CT scores of the imported cases were higher than of the indigenous cases and the lung consolidation predominance on CT findings was remarkable in the imported patients (P < 0.05).Conclusions: CT scanning not only monitored the progression of patients with COVID-19 but also reflected their exposure status to some extent. We suggest that a follow-up CT scanning interval of more than 5 days might be cost effective. The pathogenicity of novel coronavirus may be weakened through transmission under adequate quarantine measures, since indigenous cases have much better progression than imported cases.

Grapefruit-mediated fruit–drug interaction has been well discussed in clinical practice. However, the biochemical mechanisms for such interaction are far beyond our understanding. The objectives of the present study aimed at the interaction between bergaptol (BGT) and CYP2C9. BGT, one of the major furanocoumarin constituents in grapefruit, has been reported to inhibit the activity of CYP2C9. And a number of furan-containing compounds are known to act as mechanism-based inactivators of CYP2C9. In this study, BGT was found to induce time-, concentration-, and NADPH-dependent irreversible inhibition of CYP2C9. A GSH conjugate was detected in an incubation mixture containing CYP2C9, BGT, NADPH, and GSH. Further mechanistic investigation revealed that a γ-ketoenal metabolite was responsible for the enzyme inactivation. The obtained data indicate that BGT was a mechanism-based inactivator of CYP2C9. The study would facilitate the understanding of the mechanistic insight into fruit–drug interactions mediated by grapefruits.

The plant circadian clock regulates a number of central activities such as growth, flowering, abiotic and biotic stress responses, and metabolism. The PSEUDO-RESPONSE REGULATORs (PRRs) contribute to the regulation of the circadian oscillator and clock output processes. In order to elucidate the role of Oncidium PRR9, we isolated and characterized a PRR9 homolog (OnPRR9) from commercially important Oncidium ‘Gower Ramsey’. OnPRR9 encodes a 603-amino acid protein with a N-terminal REC domain and a C-terminal CCT domain. Phylogenic analysis displayed that the OnPRR9 was orthologous to other known or deduced PRR proteins at the sequence level. Examination of the transcriptional expression profile of the OnPRR9 revealed that it is subjected to circadian rhythms under the conditions of 12-h light and 12-h dark cycles (12:12LD) and continuous light (LL) but not the continuous dark (DD) conditions. Genetic complementation showed that it can partially rescue the flowering time defect of Arabidopsis mutant prr5/9 grown under the long-day (16L:8D) conditions. Overexpression analysis indicated that the OnPRR9 gene can promote flowering and inhibit hypocotyl elongation under the short-day (8L:16D) conditions. Expression pattern of the OnPRR9 gene in petals during flower development and senescence implied that it may play a role in the initiation of flower senescence. These results extend our understanding of the functional conservation of PRR9 and may provide a means of regulating flowering time of Oncidium.

Current tissue engineering strategies through scaffold-based approaches fail to recapitulate the complex three-dimensional microarchitecture and biochemical composition of the native Annulus Fibrosus tissue. Considering limited access to healthy annulus fibrosus cells from patients, this study explored the potential of bone marrow stromal cells (BMSC) to fabricate a scaffold-free multilamellar annulus fibrosus-like tissue by integrating micropatterning technologies into multi-layered BMSC engineering. BMSC sheet with cells and collagen fibres aligned at ~30° with respect to their longitudinal dimension were developed on a microgroove-patterned PDMS substrate. Two sheets were then stacked together in alternating directions to form an angle-ply bilayer tissue, which was rolled up, sliced to form a multi-lamellar angle-ply tissue and cultured in a customized medium. The development of the annulus fibrosus-like tissue was further characterized by histological, gene expression and microscopic and mechanical analysis. We demonstrated that the engineered annulus fibrosus-like tissue with aligned BMSC sheet showed parallel collagen fibrils, biochemical composition and microstructures that resemble the native disk. Furthermore, aligned cell sheet showed enhanced expression of annulus fibrosus associated extracellular matrix markers and higher mechanical strength than that of the non-aligned cell sheet. The present study provides a new strategy in annulus fibrosus tissue engineering methodology to develop a scaffold-free annulus fibrosus-like tissue that resembles the microarchitecture and biochemical attributes of a native tissue. This can potentially lead to a promising avenue for advancing BMSC-mediated annulus fibrosus regeneration towards future clinical applications.

In orthotospovirus, the nonstructural protein S (NSs) is the RNA-silencing suppressor (RSS) and pathogenicity determinant. Here, we demonstrate that a putative α-helix, designated H8, spanning amino acids 338 to 369 of the C-terminal region of the NSs protein, is crucial for self-interaction of watermelon silver mottle virus NSs protein and that the H8 affects RSS function. Co-immunoprecipitation, yeast two-hybrid, and bimolecular fluorescence complementation analyses revealed that the triple point mutation (TPM) of H8 amino acids Y338A, H350A, and F353A resulted in NSs protein self-interaction dysfunction. Transient expression of H8-deleted (ΔH8) and TPM NSs proteins in Nicotiana benthamiana plants by agroinfitration indicated that these proteins have weaker RSS activity and are far less stable than wild-type (WT) NSs. However, an electrophoretic mobility assay revealed that small interfering RNA (siRNA) binding ability of TPM NSs protein is not compromised. The pathogenicity assay of WT NSs protein expressed by the attenuated turnip mosaic virus vector restored severe symptoms in recombinant-infected N. benthamiana plants but not for ΔH8 or TPM proteins. Taken together, we conclude that the H8 helix in the C-terminal region of NSs protein is crucial for stabilizing NSs protein through self-interaction to maintain normal functions of RSS and pathogenicity, but not for NSs-siRNA binding activity.

The gastrointestinal microbiota and host co-evolve into a complex 'super-organism,' and this relationship plays a vital role in many physiological processes, such as drug metabolism. Ginseng is an important medicinal resource and the main ingredients are ginsenosides, which are less polar, difficult to absorb, and have low bioavailability. However, studies have shown that the biological activity of ginsenosides such as compound K (CK), ginsenoside Rg3 (Rg3), ginsenoside Rh2 (Rh2), 20(S)-protopanaxatriol (20(S)-PPT), and 20(S)-protopanaxadiol (20(S)-PPD) is closely related to the gastrointestinal microbiota. In this paper, the metabolic pathway of gastrointestinal microbiota-generated ginsenosides and the main pharmacological effects of these metabolites are discussed. Furthermore, our study provides a new insight into the discovery of novel drugs. Specifically, in new drug screening process, candidates with low biological activity and bioavailability should not be excluded. Because their metabolites may exhibit good pharmacological effects due to the involvement of the gastrointestinal microbiota. In addition, in further research studies to develop probiotics, a combination of agents could exert greater efficacy than single agents. Moreover, differences in lifestyle and diet lead to differences in the gastrointestinal microbiota in the human body. Therefore, administration of the same drug dose to different individuals could elicit different therapeutic effects, owing to the involvement of the gastrointestinal microbiota. Thus, treatment accuracy could be achieved by detecting the gastrointestinal microbiota before drug treatment.HighlightsGastrointestinal microbiota plays a decisive role in bioactivities of ginsenosides.The metabolic pathway and main pharmacological effects of ginsenoside metabolites are discussed.It provides new insights into novel drug discovery and further research to find probiotic, combinations to exert greater efficacy.Differences in lifestyle and diet, varies the gastrointestinal microbiota in the human body. However, the same dose of a drug producing different therapeutic effects may involve gastrointestinal microbiota.

How to prompt higher photocatalytic hydrogen production (PHP) efficiency from water to achieve practical applications still remains a big challenge with conjugated porous polymers (CPP)-based photocatalysts. Herein, we developed a simple and efficient cosolvent-assisted strategy to significantly improve the photocatalytic efficiency of CPP-based photocatalysts by introducing water-soluble aprotic bipolar co-solvents, including N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), and N-methyl pyrrolidone (NMP). The PHP activity of the pyrene–bithiophene-based CPP (named CP-St) using ascorbic acid (AA) as a sacrificial electron donor could be excellently accelerated in the presence of an aprotic bipolar NMP solvent. CP-St dispersed in an NMP/H2O/AA mixed solution under visible-light (λ > 420 nm) irradiation without the aid of a Pt cocatalyst achieved an unprecedented hydrogen evolution rate (HER) of 190.7 mmol h−1 g−1. As a result, 6 mg CP-St amazingly produced 128.1 mL H2 (∼5.72 mmol) under visible-light irradiation for only 5 h. Excitingly, by introducing 0.5 wt% Pt cocatalyst into the NMP/H2O/AA system, the HER of CP-St could be further boosted to 303.7 mmol h−1 g−1 (1.82 mmol h−1/6 mg), which represents the highest photocatalytic HER ever reported. This outstanding photocatalytic performance is mainly ascribed to the enhanced dispersity, strong hydrogen-bond interactions, and exfoliation effect by the NMP solvent. This study provides us with some new design ideas and opportunities for effectively catering to the actual hydrogen production demand.

Metalloenzyme is a source of inspiration for chemists who attempt to create versatile synthetic catalysts for aqueous catalysis. Herein, we impart metalloenzyme-like characteristics to a chiral FeII–oxazoline complex by incorporating an Fe(II) ion into a chiral oxazoline-containing discrete self-folded polymer, to realize highly enantioselective sulfa-Michael addition (SMA) in water. Intrachain FeII–oxazoline complexation together with hydrophobic interactions triggers the self-folding of the oxazoline-containing single polymeric chain in water. The formed FeII-folded single-chain polymeric nanoparticles (SCPNs) significantly accelerate the aqueous asymmetric SMA reaction via a self-folded hydrophobic compartment around the catalytic sites, reminiscent of metalloenzymatic catalysis. In addition, they can be facilely recovered for reuse by simple thermo-controlled separation due to their thermo-responsive properties. Such metallo-folded SCPNs combine the benefits of transition metal- and bio-catalyst, and avoid the tedious procedures of separation, which is a benefit for energy-saving and industrial applications.

The world currently faces an unprecedented phase of global environmental change largely driven by the combined impact of anthropogenic climate change and environmental degradation. Adaptation to global environmental changes in natural resource management is often hindered by high levels of uncertainty related to environmental impact projections. Management strategies and policies to support adaptation measures and sustainable resource management under substantial environmental uncertainty are thus urgently needed. The paper reports results of behavioral irrigation experiments with farmers and students in the region of Hangzhou in China. The experimental design simulates a small-scale irrigation system with five parties located along an irrigation channel. The first treatment adds weather variability with a drying tendency that influences water availability in the irrigation channel. In the second treatment, the participants can select one of two adaptation options. Our results suggest that participants react with a marked delay to weather uncertainty. In addition, upstream players are more likely to adapt to uncertainty than those further downstream, and groups who show higher levels of cooperation more frequently invest in adaptation measures. Lastly, extraction inequality in earlier stages is found to constitute a key obstacle to collective adaptation.

Salutogenesis is a resource-oriented approach that focuses on health creation. With the shift in focus from healthcare to health, there is a need to develop salutogenic inquiry and capacity of future nurses to promote good health and well-being in the community.This study explored nursing students' perspectives on utilising the salutogenic theory in the community for health promotion, including the scope, perceived benefits, and challenges of theory application.A qualitative study using framework analysis.A tertiary institution in Singapore.Nursing students who were taught the salutogenic theory for 'Healthy Community Living' module.Data were gathered from four focus group discussions (n = 18) and 32 students' written assignments. They were analysed based on five components of knowledge framework.Four themes were identified: re-orienting healthcare for healthy living communities; ambivalent learning experiences; attracting early adopters of salutogenic paradigm; and practices for positive health development in complex systems: future directions. Findings reflected the value, versatility, and usefulness of introducing the salutogenic paradigm into the curriculum of healthcare education. Practical know-hows of applying the theory in community practice and development of health intervention were elicited.Much work is needed to future-proof the next generation of nurses in embracing and unifying the concept of salutogenic science into the existing pathogenic-driven care model. The real challenge would be the continual support of nursing education and health system to provide salutogenic care in the community.

The 17q12 microdeletion syndrome is a type of syndrome caused by a deletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome. The main clinical features of the syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. The diverse range of phenotypes associated with 17q12 microdeletion limited clinical recognition and diagnosis. In addition, the phenotypic description of this microdeletion is mainly about postpartum. Due to the rarity of the 17q12 microdeletion itself, studies on the prenatal phenotype of the 17q12 microdeletion are limited. This study aims to analyze the prenatal ultrasound features of 17q12 microdeletion, and to investigate the possibility of genotype-phenotype relationship for providing evidence for genetic counseling in such pregnancies.A total of 3 320 pregnant women and their fetuses were collected for the detection of chromosome copy number variation sequencing (CNV-Seq) due to different ultrasound anomalies in Xiangya Hospital of Central South University. The clinical data of pregnant women and their fetuses who were found to harbor 17q12 microdeletion were reviewed, including maternal age, fetus ultrasound findings, gestational week of the invasive procedure, CNV-Seq results, and the pregnancy outcome. CNV-Seq was tested in the parents to verify whether the abnormality was de novo or inherited. The prenatal ultrasound features and CNV-Seq test results of these 12 fetuses were analyzed and their pregnancy outcomes were followed up.Approximately 0.36% (12/3 320) of fetuses were detected to have 17q12 microdeletion, all characterized as renal abnormalities, accounting for 4.2% (12/288) of all prenatal ultrasound with renal abnormalities, accounting for 48% (12/25) of prenatal ultrasound with renal abnormalities and pathogenic chromosomal abnormalities. The sizes of 17q12 deletion ranged from 1.4 to 1.7 Mb, and all of them included the HNF1B gene. Nine cases were de novo, 2 inherited from the mother, and 1 inherited from father. Among 12 fetuses with 17q12 deletion, 11 cases of prenatal ultrasound suggested bilateral hyperechogenic kidneys and 1 case only showed renal cyst, in which 3 fetuses with enlarged kidneys, 1 with clubfeet, and 1 with subependymal cyst. Pregnancy outcomes were available for 11 of the 12 fetuses. Of them, the parents of 9 fetuses with de novo deletion chose to terminate the pregnancy, and 2 live birth babies inherited from their mother with normal renal function had persistent renal echogenicity enhancement after birth.Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first-line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000-5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C

Control of plant viruses by cross-protection is limited by the availability of effective protective strains. Incorporation of an NIa-protease processing site in the extreme N-terminal region of the helper component protease (HC-Pro) of turnip mosaic virus (TuMV) resulted in a mutant virus TuHN