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Abstract Background As of September 2023, more than 1,000 cases of monkeypox (mpox) have been reported in China. Based on the available evidence, men who have sex with men (MSM) are at high risk for mpox infection. This study aimed to analyses the self-reported infection status, knowledge, attitude and influencing factors of monkeypox among MSM in Jiaxing City, China. Methods A web-based cross-sectional survey was conducted in September 2023 to gather data on participants’ socio-demographic profiles, mpox-related knowledge, sexual behavior characteristics, and other potentially related information to mpox knowledge. Multivariate regression modeling was employed to analyze the factors influencing the level of mpox-related knowledge. Results A total of 562 MSM were recruited; 4.3% self-reported being HIV-positive, 83.3% of respondents had heard of mpox, and 2.3% of them reported having suspected symptoms. 89.7% of respondents were willing to be vaccinated against mpox, but only 24.8% had a high level of knowledge about mpox. The main factors influencing knowledge of mpox were education level, household registration, homosexual anal intercourse in the past 6 months, and taking the HIV pre-exposure prophylaxis (PrEP). Conclusions Knowledge of mpox among MSM living in the Jiaxing area needs to be enhanced, but willingness to get vaccinated is high. Educational level, household location, sexual behavior and PrEP use have important effects on knowledge of mpox. Individuals exhibiting symptoms indicative of suspected mpox had a diminutive consultation frequency, and it is imperative to augment screening efforts for mpox symptoms within specific demographic groups to prevent the underreporting of mpox cases.

Abstract Background The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure–function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). Methods A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient’s whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein–protein docking (HADDOCK) algorithm and protein–ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. Results Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. Conclusion Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Abstract Investigating interface engineering by piezoelectric, flexoelectric and ferroelectric polarizations in semiconductor devices is important for their applications in electronics, optoelectronics, catalysis and many more. The interface engineering by polarizations strongly depends on the property of interface barrier. However, the fixed value and uncontrollability of interface barrier once it is constructed limit the performance and application scenarios of interface engineering by polarizations. Here, we report a strategy of tuning piezotronic effect (interface barrier and transport controlled by piezoelectric polarization) reversibly and accurately by electric pulse. Our results show that for Ag/HfO2/n-ZnO piezotronic tunneling junction, the interface barrier height can be reversibly tuned as high as 168.11 meV by electric pulse, and the strain (0–1.34‰) modulated current range by piezotronic effect can be switched from 0–18 nA to 44–72 nA. Moreover, piezotronic modification on interface barrier tuned by electric pulse can be up to 148.81 meV under a strain of 1.34‰, which can totally switch the piezotronic performance of the electronics. This study provides opportunities to achieve reversible control of piezotronics, and extend them to a wider range of scenarios and be better suitable for micro/nano-electromechanical systems.

Abstract Intriguing “slidetronics” has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), NLRP3−/− and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1β production, proliferation and migration were attenuated in NLRP3−/− VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

Introduction:Current clinical research has reported the effectiveness and safety of venetoclax in combination with hypomethylating agents (VEN-HMA) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Thus, this study aimed to examine the effectiveness and safety of VEN-HMA therapy in patients with MDS and CMML and compared its short-term and long-term therapeutic effects with HMA monotherapy.Method:We analyzed data from our center, comprising 19 patients with MDS and CMML who received VEN-HMA therapy, compared to 32 patients treated with HMA monotherapy.Results:The overall response rate (ORR) in the VEN-HMA group was 73.7%, compared to 59.4% in the HMA group. The survival analysis revealed that the median overall survival (mOS) time in the VEN-HMA group was 16 months, with a median progression-free survival (mPFS) time of 9 months, both of which were longer than those observed in the HMA group (p < 0.05). Key adverse events (AEs) included grade 3–4 neutropenia (89.5% in VEN-HMA group vs. 87.5% in HMA group), grade 3–4 thrombocytopenia (73.7% vs. 71.9%), and anemia (73.7% vs. 90.6%). Infection of grade 3 or higher occurred in 63.2% of patients in the VEN-HMA group and 65.6% of patients in the HMA group.Discussion:Our study has confirmed the effectiveness and safety of the combined treatment of HMAs and venetoclax, which offers significant advantages to patients due to the relatively high and rapid response rates.

BackgroundTuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults.MethodsAll notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China’s TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored.ResultsFrom January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05–1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28–2.26), passive case finding (AOR: 1.46, 95% CI: 1.07–1.98) and retreatment (AOR: 1.52, 95% CI: 1.11–2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53–0.90) and non-students (AOR: 0.83, 95% CI: 0.71–0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29–1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32–1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30–1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78–1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59–0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before.ConclusionIn general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.

Abstract Mechanical sensors are mainly divided into two types (vertical force sensing and lateral strain sensing). Up to now, one sensor with two working modes is still a challenge. Here, we demonstrate a structural design concept combing a piezoelectric nano/microwire with a flexible polymer with protrusions that enables a dual-modal piezotronic transistor (DPT) with two working modes for highly sensitive vertical force sensing and lateral strain sensing. For vertical force sensing, DPT exhibits a force sensitivity up to 221.5 N−1 and a minimum identifiable force down to 21 mN, corresponding to a pressure sensitivity of 1.759 eV/MPa. For lateral strain sensing, DPT can respond to a large compression strain (~5.8%) with an on/off ratio up to 386.57 and a gauge factor up to 8988.6. It is a universal design that can integrate vertical force sensing and lateral strain sensing into only one nanodevice, providing a feasible strategy for multimodal devices.

To characterize the complex creep behavior of steel slag–asphalt mixture influenced by both stress and temperature, predictive models employing Back Propagation (BP) and Long Short-Term Memory (LSTM) neural networks are described and compared in this paper. Multiple stress repeated creep recovery tests on AC-13 grade steel slag–asphalt mix samples were conducted at different temperatures. The experimental results were processed into a group of independent creep recovery test results, then divided into training and testing datasets. The K-fold cross-validation was applied to the training datasets to fine-tune the hyperparameters of the neural networks effectively. Compared with the experimental curves, both the effects of BP and LSTM models were investigated, and the broad applicability of the models was proven. The performance of the trained LSTM model was observed by a 95% confidence interval around the fit errors, thereby the creep strain intervals for the testing dataset were obtained. The results suggest that the LSTM model had enhanced prediction compared the BP model for creep deformation trends of steel slag–asphalt mixture at various temperatures. Due to the potent generalization strength of artificial intelligence technology, the LSTM model can be further expanded for forecasting road rutting deformations.

The huge development of micro-/nano-manufacturing techniques on different materials has greatly expanded the possibilities of realizing on-chip multifunctional devices on photonic integrated circuits. In recent years, we have witnessed technological advancements, such as active photonic applications through hybrid integration. In this Perspective, we first summarize the integrated photonic materials, hybrid integration technologies, and corresponding coupling techniques in hybrid integration and give the technique prospects. We also introduce significant advances in hybrid integration technologies for active photonic applications, such as laser sources, optical frequency combs, and modulators, and give our views that are likely to develop rapidly. Finally, we discuss the challenges in hybrid technologies and photonic applications.

The ongoing pace of urbanization poses a substantial obstacle to the concurrent progress of both financial and ecological development. Recognizing this challenge, governments globally are formulating cutting-edge strategies for urban renewal to ensure the long-term sustainability of cities. In this context, we employ a difference-in-differences model to scrutinize the intricate relationship between smart cities and the growth of renewable energy, utilizing the Chinese smart city pilot program as a pertinent experiment. This analytical approach provides novel insights into the underlying reasons behind this correlation. The research yields three noteworthy findings. Firstly, it underscores the indispensable role of pilot initiatives in smart cities for advancing the cause of renewable energy. Secondly, the study reveals a positive and beneficial interplay between creativity, economic inclusion, and the utilization of technological innovation in experimental urban programs, suggesting a potential multiplier effect. Thirdly, the local context significantly influences the impact of smart city pilots, with the dissemination of renewable energy being particularly effective in resource-rich, metropolitan, and coastal cities. Observable impacts of current smart city experiment on energy security and sustainable development are already apparent. The research findings contribute fresh perspectives to the complex challenges of sustainable energy production and urban planning, especially in developing countries like China.

Abstract Background Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized. Methods This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately. Results Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p

Antibody arrays play a pivotal role in the detection and quantification of biomolecules, with their effectiveness largely dependent on efficient protein immobilization. Traditional methods often use heterobifunctional cross-linking reagents for attaching functional residues in proteins to corresponding chemical groups on the substrate surface. However, this method does not control the antibody’s anchoring point and orientation, potentially leading to reduced binding efficiency and overall performance. Another method using anti-antibodies as intermediate molecules to control the orientation can be used but it demonstrates lower efficiency. Here, we demonstrate a site-specific protein immobilization strategy utilizing OaAEP1 (asparaginyl endopeptidase) for building a nanobody array. Moreover, we used a nanobody-targeting enhanced green fluorescent protein (eGFP) as the model system to validate the protein immobilization method for building a nanobody array. Finally, by rapidly enriching eGFP, this method further highlights its potential for rapid diagnostic applications. This approach, characterized by its simplicity, high efficiency, and specificity, offers an advancement in the development of surface-modified protein arrays. It promises to enhance the sensitivity and accuracy of biomolecule detection, paving the way for broader applications in various research and diagnostic fields.

BackgroundTuberculosis (TB) remains a major public health challenge. However, indicators of delays in assessing effective TB prevention and control and its influencing factors have not been investigated in the eastern coastal county of China.MethodsAll notified pulmonary tuberculosis (PTB) cases in the Fenghua District, China were collected between 2010 and 2021 from the available TB information management system. Comparison of delays involving patient, health system, and total delays among local and migrant cases. Additionally, in correlation with available Basic Public Health Service Project system, we performed univariate and multivariate logistic regression analyses identified the influencing factors associated with patient and total delays in patients aged >60 years.ResultsIn total, 3,442 PTB cases were notified, including 1,725 local and 1,717 migrant patients, with a male-to-female ratio of 2.13:1. Median patient and total delays of local TB patients were longer than those for migrant patients; the median health system delay did not show any significant difference. For patient delay among the older adult, female (cOR: 1.93, 95% CI: 1.07–3.48), educational level of elementary school and middle school (cOR: 0.23, 95% CI: 0.06–0.84) had a statistical difference from univariable analysis; however, patients without diabetes showed a higher delay for multiple-factor analysis (aOR: 2.12, 95% CI: 1.02–4.41). Furthermore, only the education level of elementary school and middle school presented a low total delay for both univariate (cOR: 0.22, 95% CI: 0.06–0.82) and multivariate analysis (aOR: 0.21, 95% CI: 0.05–0.83) in the older patients.ConclusionThe delay of TB cases among migrants was lower than the local population in the Fenghua District, which may be related to the “healthy migrant effect”. It highlights that women, illiterate people, and people without diabetes are key groups for reducing delays among older adults. Health awareness should focus on these target populations, providing accessible health services, and reducing the time from symptom onset to diagnosis.

This work focused on the problem of high arsenic (As) residues in kelp polysaccharides and develops an effective method for removing As from kelp polysaccharides. Lavoisier Frameworks material (MIL-88A) was assembled with Polyurethane foam (PU). Scanning electron microscopy (SEM), Fourier infrared spectroscopy (FTIR), and X-ray diffraction spectroscopy (XRD) were used to characterize the morphology and surface functional group of MIL-88A/PU materials, and then atomic fluorescence spectroscopy (AFS) was used to investigate the ability of MIL-88A/PU to remove As. Results showed that MIL-88A was successfully loaded on PU, and the MIL-88A/PU possesses abundant active sites. The maximum adsorption capacity for As (III) was 107.52 mg/g when the absorption conditions maintained at 298 K, pH5.0, and 240 min. After treating by MIL-88A/PU, the amount of As in kelp polysaccharides were effectively reduced, and the removal rate of total As and inorganic As was 70.43% and 73.33%, respectively. Moreover, the preservation rates of polysaccharide and protein content in kelp polysaccharides were 90.47% and 73.76%, respectively. Remarkably, dealing kelp polysaccharides with MIL-88A/PU significantly reduced the amount of As, which would improve the economic benefit of the kelp polysaccharides.

In this study, we conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in various sexual risk behaviour groups in a developed area in eastern China based on phylogenetic inference, molecular transmission networks, and Bayesian analyses. A total of 1083 pol sequences (91.23%, 1083/1187) from newly diagnosed HIV-1-positive patients from 2017 to 2020 were successfully obtained and involved thirteen HIV-1 subtypes, in which the major HIV-1 subtypes were CRF07_BC (36.10%, 391/1083) and CRF01_AE (34.63%, 375/1083). 485 individuals (44.78%,485/1083) formed 146 clusters in the network. Of which CRF07_BC showed extensive clustering driven by men who have sex with men (MSM) within larger networks, CRF01_AE and other subtypes were generally driven by small clusters (SCs) and medium clusters (MCs) among various risk groups. Through Sankey diagrams, the MSM group infected with CRF07_BC had a greater impact on the non-commercial heterosexual group among all cross-risk groups. In addition, a higher number of key individuals infected with CRF07_BC (40.22%, 74/127), suggests the crucial role of CRF07_BC-infected individuals as a local epidemic driver in the context of a mixed HIV-1 epidemic. Further Bayesian analysis confirmed that CRF07_BC was introduced into Jiaxing city from other provinces multiple times and spread rapidly among MSM and heterosexual individuals. Overall, our study provided some insights and information to explore the local transmission dynamics of HIV-1 epidemic strains involving various sexual risk groups, and emphasize that it is necessary to conduct in-depth research and precise intervention targeting key clusters/ individuals to effectively block the continued transmission of AIDS.

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

We find that when a major customer has greater market power in its industry, its supplier firm exhibits better performance. The effect of the major customer’s market power on its supplier’s performance is more pronounced when the economic bonding between the customer firm and the supplier is stronger, when the customer firm is geographically closer to its supplier, and when the relationship between the two firms matures. Furthermore, we document that a customer firm’s product market power increases demand stability for its supplier, reduces the supplier’s cost of debt, and improves the supplier’s investment efficiency.

With the rapid development of Chinese urbanization and industrialization level, the Chinese real estate transaction area continues to grow, and the country's decoration industry is expanding. Due to the rapid expansion, the decoration industry has failed to establish a good industry order, and the current decoration industry has many problems, such as opaque information and low industrial efficiency. Traditional and Internet decoration companies have failed to solve these problems effectively. The purpose of this study is to build a new collaborative decoration platform to solve the shortcomings of the decoration industry and promote its healthy development. A crowd-based collaborative decoration platform called Crowd E-home is proposed. Based on the Building Information Modeling (BIM) of houses, the platform constructs collaborative intelligent digital models, which have the characteristics of evolution, coordination, multifaceted, and initiative. These models act as intermediate coordinators to complete the collaborative division of labor. This platform plays a role in matching multiparty transactions among consumers, designers, construction teams, material suppliers, and supervisors to solve the problem of the huge coordination costs of traditional decoration companies. It also breaks the space-time limit of consumer selection during the decoration process, improves the decision-making power of consumers, and meets consumer needs for personalized services. The collaborative concept of the platform and the application of BIM optimize the existing decoration industry chain, which transforms the traditional chain model into a star-shaped decoration closed-loop ecosystem.

Heart failure with preserved ejection fraction (HFpEF) is typically preceded by cardiac hypertrophy. Lycium barbarum L. as functional food show the health benefits of cardiovascular diseases. Whether Lycium barbarum L. protein-derived angiotensin-converting enzyme inhibitory peptide (ACEIP) has effects on improving cardiac hypertrophy is unknown. Here, HFpEF mouse model was established by a high-fat diet and 0.5 g/L Nѡ-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in drinking water. Interventricular septum thickness (IVS), left ventricular posterior wall thickness (LVPW), left ventricular diameter (LVD), ejection fraction (EF) and left ventricular mass (LV Mass) were evaluated by transthoracic echocardiography. Serum n-terminal pro-brain natriuretic peptide (NT-proBNP), Ang II, Ang (1–7) concentrations were measured by ELISA, and hypertrophy by WGA staining. We found that ACEIP significantly improved diastolic dysfunction as reflected by the increase in mitral inflow E and A wave ratio (E/A ratio) and decrease in isovolumic relaxation time (IVRT). Meanwhile, LV Mass, IVS, LVPW and LVD in systolic or diastolic period were significantly reduced by ACEIP. Furthermore, ACEIP reversed protein kinase C β1 (PKCβ1) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which were related to ACE2/Ang (1–7)/MasR axis activation. Our findings indicated that ACEIP could be a potential nutritional approach for the intervention of HFpEF.

The blockchain, with its key characteristics of decentralization, persistence, anonymity, and auditability, has become a solution to overcome the overdependence and lack of trust for a traditional public key infrastructure on third-party institutions. Because of these characteristics, the blockchain is suitable for solving certain open problems in the service-oriented social network, where the unreliability of submitted reviews of service vendors can cause serious security problems. To solve the unreliability problems of submitted reviews, this paper first proposes a blockchain-based identity authentication scheme and a new trusted service evaluation model by introducing the scheme into a service evaluation model. The new trusted service evaluation model consists of the blockchain-based identity authentication scheme, evaluation submission module, and evaluation publicity module. In the proposed evaluation model, only users who have successfully been authenticated can submit reviews to service vendors. The registration and authentication records of users’ identity and the reviews for service vendors are all stored in the blockchain network. The security analysis shows that this model can ensure the credibility of users’ reviews for service vendors, and other users can obtain credible reviews of service vendors via the review publicity module. The experimental results also show that the proposed model has a lower review submission delay than other models.

Covalent inhibitors targeting the main protease (Mpro, or 3CLpro) of SARS-CoV-2 have shown promise in preclinical investigations. Herein, we report the discovery of two new series of molecules that irreversibly bind to SARS-CoV-2 Mpro. These acrylamide containing molecules were discovered using our covalent DNA-encoded library (DEL) screening platform. Following selection against SARS-CoV-2 Mpro, off-DNA compounds were synthesized and investigated to determine their inhibitory effects, the nature of their binding, and to generate preliminary structure-activity relationships. LC-MS analysis indicates a 1:1 (covalent) binding stoichiometry between our hit molecules and SARS-CoV-2 Mpro. Fluorescent staining assay for covalent binding in the presence of cell lysate suggests reasonable selectivity for SARS-CoV-2 Mpro. And lastly, inhibition of enzymatic activity was also observed against a panel of 3CLpro enzymes from different coronavirus strains, with IC50 values ranging from inactive to single digit micromolar. Our results indicate that DEL selection is a useful approach for identifying covalent inhibitors of cysteine proteases.

Strain-induced piezoelectric polarization can be used to modulate the interface electrical transport. Here, the authors achieved a piezotronic tunneling strain sensor at device scale with optimized performance based on the structure of Ag/HfO2/n-ZnO.

Abstract Background UBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified. Methods UBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene. Results Here we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression. Conclusions Our study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.

Abstract The BEPCII project is for upgrading the Beijing Electron Positron Collider to reach a higher luminosity. The cryogenic system has been firstly designed and deployed in BEPCII, which provides cooling capacity for SRF cavities, SCQ and SSM. The cryogenic control system consists of Siemens PLC for the refrigerator control and “PLC + IOC” for superconducting device control. The BEPCII machine commissioning with beam started in October 2006. This paper describes the design and the development of the cryogenic control system.

To protect the germplasm resources of Schizothorax biddulphi, we developed and used 20 pairs of polymorphic microsatellite primers to analyze the genetic diversity and structure of populations. A total of 126 samples were collected from the Qarqan River (CEC), Kizil River (KZL), and Aksu River (AKS) in Xinjiang, China. The results showed that 380 alleles were detected in 20 pairs of primers and the average number of alleles was 19.0. The effective allele numbers and Nei’s gene diversity ranged from 1.1499 to 1.1630 and 0.0962 to 0.1136, respectively. The Shannon index range suggested low levels of genetic diversity in all populations. The genetic distance between the CEC and AKS populations was the largest, and the genetic similarity was the smallest. There was a significant genetic differentiation between CEC and the other two populations. The UPGMA clustering tree was constructed based on population genetic distance, and the clustering tree constructed by individuals showed that the AKS population and KZL population were clustered together, and the CEC population was clustered separately. Also, the group structure analysis also got the same result. It can be seen that although the three populations of S. biddulphi do not have high genetic diversity, the differentiation between the populations was high and the gene flow was limited, especially the differentiation between the CEC population and the other two populations. This study not only provided genetic markers for the research of S. biddulphi but the results of this study also suggested the need for enhanced management of S. biddulphi populations.

Graphene oxide (GO), owing to its atomic thickness and tunable physicochemical properties, exhibits fascinating properties in membrane separation fields, especially in water treatment applications (due to unimpeded permeation of water through graphene-based membranes). Particularly, GO-based membranes used for desalination via pervaporation or nanofiltration have been widely investigated with respect to membrane design and preparation. However, the precise construction of transport pathways, facile fabrication of large-area GO-based membranes (GOMs), and robust stability in desalination applications are the main challenges restricting the industrial application of GOMs. This review summarizes the challenges and recent research and development of GOMs with respect to preparation methods, the regulation of GOM mass transfer pathways, desalination performance, and mass transport mechanisms. The review aims to provide an overview of the precise regulation methods of the horizontal and longitudinal mass transfer channels of GOMs, including GO reduction, interlayer cross-linking, intercalation with cations, polymers, or inorganic particles, etc., to clarify the relationship between the microstructure and desalination performance, which may provide some new insight regarding the structural design of high-performance GOMs. Based on the above analysis, the future and development of GOMs are proposed.

BackgroundWe aimed to generate and validate a nomogram to predict patients most likely to require intensive care unit (ICU) admission following gastric cancer surgery to improve postoperative outcomes and optimize the allocation of medical resources.MethodsWe retrospectively analyzed 3,468 patients who underwent gastrectomy for gastric cancer from January 2009 to June 2018. Here, 70.0% of the patients were randomly assigned to the training cohort, and 30.0% were assigned to the validation cohort. Least absolute shrinkage and selection operator (LASSO) method was performed to screen out risk factors for ICU-specific care using the training cohort. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction nomogram. The calibration and discrimination of the nomogram were evaluated in the training cohort and validated in the validation cohort. Finally, the clinical usefulness was determined by decision curve analysis (DCA).ResultsAge, the American Society of Anesthesiologists (ASA) score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were selected for the model. The concordance index (C-index) of the model was 0.843 in the training cohort and 0.831 in the validation cohort. The calibration curves of the ICU-specific care risk nomogram suggested great agreement in both training and validation cohorts. The DCA showed that the nomogram was clinically useful.ConclusionsAge, ASA score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were identified as risk factors for ICU-specific care after gastric surgery. A clinically friendly model was generated to identify those most likely to require intensive care.

Abstract Lapatinib is widely used in the later lines treatment of HER2 positive metastatic breast cancer (MBC). EGF104900 study suggested that among patients who experienced progression on prior trastuzumab‐containing regimens, lapatinib plus trastuzumab had better effects than trastuzumab alone. However, no evidence was discovered in terms of lapatinib plus capetabine compared with lapatinib plus trastuzumab plus chemotherapy, as well as a treatment after progression on lapatinib. We evaluated the medical records retrospectively of all MBC patients with HER2 positive disease who progressed on prior trastuzumab‐containing regimens (advanced setting) and a taxane (any setting) and received lapatinib‐based treatment from 2015 to 2018 in five institutions in China. A total of 242 patients were available for analysis. Among them, 164 (68%) patients received lapatinib plus capetabine (LX) and 78 (32%) patients received lapatinib plus trastuzumab and one chemotherapy (HLC). The median progression‐free survival (PFS) of the HLC group was significantly superior to the LX group (8.8 months vs 5.0 months, P

Niobium nitride (NbN) nanowires have a high repetition rate and efficiency, making them ideal for superconducting nanowire single photon detectors (SNSPDs). However, it is difficult to fabricate NbN arrays over large areas, which is critical for various applications. This paper describes a 4 × 4 NbN SNSPD array (16 pixels) and optical coupling with a 300-μm-diameter multimode fiber using beam compression technology. This is the first NbN SNSPD coupled with such large-diameter fibers. The designed pixels are positioned as closely as possible (pixel filling factor about 98.5%), almost without dead area between them. This results in a system efficiency of 46% and a quantum efficiency of 94.5% for photons (λ = 1064 nm) coupled from multimode fibers. An intrinsic time resolution of less than 69 ps can be obtained. The proposed high-performance single photon detector is suitable for satellite laser ranging. Furthermore, the proposed system is feasible for large SNSPD arrays with NbN, paving the way for the development of efficient photon cameras with NbN nanowires.

Lightning disturbance may be misjudged as dc fault by the primary protection in the flexible high voltage dc (HVDC) grid. To solve this problem, an auxiliary fault identification strategy based on convolutional neural network with branch structures (BR-CNN) is proposed in this paper. In the proposed scheme, the voltage and current characteristic matrix is constructed as the input matrix of BR-CNN model and the output categories include positive pole-to-ground (PTG) fault and lightning disturbance. Voltage and current branches are constructed to extract high-level local features of input data layer by layer, and main branch is designed to realize the comprehensive utilization of voltage and current information. Through autonomous learning of the model, the nonlinear mapping relationship between input and output is constructed. The method only uses the single-terminal quantities, and can be used as an auxiliary criterion to improve the reliability of the primary protection. The test results verify the effectiveness of the method, and the recognition accuracy is better than the traditional classification models.

ObjectiveWe previously established a gross tissue response (GTR) system to evaluate the intraoperative response of perigastric tissue in patients with gastric cancers to neoadjuvant chemotherapy. This prospective cohort study aims to confirm the relationship between gross tissue response and clinicopathological characteristics and explore the possibility of using the GTR system to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.MethodsA total of 102 patients with gastric cancer from January 2019 to April 2020 were enrolled in this study. The degrees of fibrosis, edema, and effusion in the perigastric tissues were assessed intraoperatively according to the GTR system. We systematically analyzed the relations between GTR and clinicopathological characteristics, and then a prediction model that includes GTR was established to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.ResultsFinally, the study included 71 male patients and 31 female patients. The patients had an average age of 58.79 ± 1.03 years, BMI of 22.89 ± 0.29, and tumor diameter of 4.50 ± 0.27 cm. Among these patients, 17 underwent laparoscopic gastrectomy, 85 underwent open gastrectomy, the average operation time was 294.63 ± 4.84 minutes, and the mean volume of intraoperative blood loss was 94.65 ± 5.30 ml. The overall 30-day postoperative complication rate was 19.6% (20/102). The total GTR was significantly related to the primary tumor stage, operation time and 30-day postoperative complication rate (p

BackgroundPyrotinib is a newly-developed irreversible pan-ErbB (erythroblastic leukemia viral oncogene homolog) receptor oral tyrosine kinase inhibitor (TKI) with promising efficacy in the human epidermal growth factor receptor-2 (HER2) positive breast cancer. The phase III PHOEBE study proved that pyrotinib plus capecitabine exceeded lapatinib plus capecitabine (LX) in PFS (p < 0.001). Oral vinorelbine is commonly used in combination with anti-HER2 treatment. However, no evidence was reported in terms of the real-world pattern, safety, and efficacy of pyrotinib plus vinorelbine (NP) compared with LX.MethodsMedical records were retrospectively evaluated for all HER2-positive metastatic breast cancer (MBC) patients who experienced progression on prior trastuzumab-containing regimens (advanced setting) and taxane (any setting) and received NP or LX therapy from 2015 to 2021 in five institutions.ResultsA total of 224 patients were enrolled and evaluated, of which 132 (58.9%) patients received LX and 92 (41.1%) patients received NP. The median progression-free survival (mPFS) of NP group was significantly longer than that in LX group (8.3 vs 5.0 months, HR = 0.47 95% CI 0.34–0.65, p < 0.001). The advantage of NP over LX was seen both in patients with trastuzumab resistance (p < 0.001) and refractoriness (p = 0.004). The NP group had more diarrhea cases (23.9%) compared to the LX group (8.3%). Discontinuation rates in the two groups were similar.ConclusionsThis trial revealed the clinical practice of NP and LX treatment among HER2+ MBC patients pretreated with trastuzumab in China. More patients received LX than NP in real-world while the efficacy of NP exceeded LX in terms of PFS regardless of resistant status of trastuzumab. Although the NP group had more diarrhea cases, toxicities in both groups were acceptable.

Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.

Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Patients and Methods: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m 2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusion: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

The continuously annealed low-carbon-steel strips from industrial production showed an average aging index of about 30 N/mm². This increase in yield strength caused by the continuous-annealing process was strongly dependent on the soaking temperature and the soaking time. Whilst the optimization of the overaging parameters and the use of a higher annealing temperature would reduce the ageing susceptibility of low-carbon-steel strips, it was considered unlikely that its magnitude could be reduced to a comparable level to that of the batch-annealed one. Within the limit of low-carbon-strip specifications, there was very little effect of the C content on the ageing. The aging index of the temper-rolled materials decreased with the increase in the temper-rolling reductions, and a maximum increase in yield strength was achieved at a temper-rolling reduction of about 1%. In this work, the effect of C content, Al content, continuous-annealing cycles, and temper-rolling reduction on the ageing susceptibility of the continuously annealed low-carbon-steel strips was examined. SEM/EBSD technique was developed to characterize the temper-rolling strain bands and to assess the effect of temper-rolling reduction on the yield strength of the low-carbon-steel strips.

Introduction: Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. Methods: The study included 200 patients with HR+/HER2– MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. Results: A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane ( n = 29), capecitabine ( n = 21), and vinorelbine ( n = 17), while the endocrine therapy regimens were chidamide plus exemestane ( n = 16) and everolimus plus exemestane ( n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups ( p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy ( p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively ( p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively ( p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Conclusions: Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2– MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment. ClinicalTrials.gov identifier: NCT04517318

IntroductionPyrotinib plus capecitabine has been approved in China for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Meanwhile, vinorelbine is another important chemotherapy option for MBC available in oral and intravenous forms. Thus, pyrotinib plus vinorelbine may represent a new treatment option, particularly for patients with failed capecitabine treatment. This study reported the first real-world data for pyrotinib plus vinorelbine therapy in HER2+ MBC.MethodsHER2+ MBC patients (n = 97) treated with pyrotinib plus vinorelbine in six institutions across China from May 2018 to June 2020 were enrolled. Progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and toxicity profiles were determined.ResultsSixty-seven percent of patients received more than two lines of systematic therapy. Nearly all patients (97.9%) had received trastuzumab and 50.5% were administered lapatinib. When combined with pyrotinib, 74.2% received oral and 25.8% received intravenous vinorelbine. Median PFS (mPFS) was 7.8 (range, 4.7–10.8) months for all patients. The mPFS in patients administered pyrotinib as second-line therapy and third-or-higher-line therapy were 12.0 and 6.4 months, respectively. Patients who received pyrotinib plus oral or intravenous vinorelbine had similar mPFS (7.8 vs. 6.4 months, p = 0.871). The 23 patients with brain metastases had mPFS of 6.3 (range, 3.4–9.2) months. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (10.8 months vs. 5.6 months, p = 0.020). Median OS was not achieved. The ORR for 96 patients was 34.3%. Common grade 3 and 4 adverse events were diarrhea (22.7%), neutropenia (7.2%), and leukopenia (4.1%).ConclusionsPyrotinib plus vinorelbine therapy demonstrated promising effects in HER2+ MBC with tolerable toxicity, particularly in patients with second-line treatment and without prior lapatinib treatment, as well as in patients with brain metastases. Oral vinorelbine is a useful alternative to the intravenous form when combined with pyrotinib.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04517305].

166.6-MHz superconducting cavities have been chosen for the High Energy Photon Source (HEPS) as the main accelerating structures to provide 900 kW of beam power and 5.4 MV of accelerating voltage. A proof-of-principle cavity adopting the quarter-wave beta = 1 geometry was previously developed. Excellent performance was achieved in vertical tests at cryogenic temperatures. The cavity was later welded with a helium jacket, dressed with a power coupler and other ancillaries, and high-power tested in a test cryomodule. Performance degradation was observed and analyzed. Evidence from temperature sensor readout and heat loss measurement results suggested an overheating in the cavity–coupler interface region causing a “thermal runaway” and eventually quenching the cavity at its design voltage. Electromagnetic-fluid-thermal coupled simulation has thus been conducted, and the hypothesis was nicely validated. Finally, solutions were proposed including an elongated niobium extension tube at the coupler port and an optimized helium gas cooling of the power coupler’s outer conductor. These modifications have been subsequently applied on the 166.6-MHz higher-order-mode damped superconducting cavities for the HEPS. Heat loss at 4.2 K contributed by the power coupler can be largely reduced with a modest gas cooling scheme. Similar design approaches can also be applied to other non-elliptical superconducting structures with on-cavity high-power coupler mountings.

The modular multilevel converter (MMC) has a promising prospect in high voltage direct current (HVDC) transmission, while the application of MMC is limited by lacking of dc fault interruption capability. Hence, an enhanced MMC topology with the flexible interruption capability of dc fault is proposed to handle this problem on the basis of the exiting dc fault blocking technology. The enhanced flexible interruption MMC (EFI-MMC) makes two improvements in topology compared with the traditional MMC, which adapts quasi-half bridge sub-module (QHBSM) and adds the bridge arm power consumption circuit. The QHBSM can interdict the infeed current from the ac system when dc-side fault occurs by combined with reverse voltage control strategy. Meanwhile, the residual energy of arm reactor and dc smoothing reactor can be absorbed by the arm power consumption circuit to suppress the voltage stress of reactors, which can reduce the technical requirements of arrester. Finally, a ±200kv EFI-MMC simulation system is built to verify the validity of the proposed topology.

This paper proposes a collaborative optimal configuration method of current limiting reactors (CLRs) and fault current limiters (FCLs) in the modular multilevel converter (MMC)-based high voltage direct current (HVDC) grids. The calculation methods of dc line fault currents and bridge arm fault currents considering the collaboration of CLRs and FCLs have high accuracy. The multi-objective optimization configuration model is established, in which the fault current limiting effect, the total inductances of CLRs and the number of FCLs are used as objective functions while the DCCBs current breaking capacity, the converter valves overcurrent protection, the boundary of the dc line protection area, the dynamic performance of the dc system and the converter station outlet dc voltage are used as constraints. In this paper, the multi-objective optimization algorithm is used to solve multi-objective optimal configuration problem for the CLRs and FCLs. Finally, the proposed method is tested with a symmetrical monopole four-terminal MMC-HVDC grid in PSCAD/EMTDC. The simulation results verify that the proposed optimal configuration method can ensure the continuous and reliable operation of the dc grid under dc faults.

Objectives—To investigate the clinical characteristics, managements, outcome, and evaluate the risk factors of Multisystem (MS) Langerhans Cell Histiocytosis (LCH) with diverse skin lesions as the first sign in four young infants. Methods—Their clinical features, disease progression, therapy, and outcomes were reviewed and analyzed retrospectively. Results—The average onset age of skin lesions was about 2 months. Cases 1 and 2 had risk organs involved (RO+) and a lack of bone lesions, and progression could not be reversed by systemic chemotherapy. They both died eventually. Cases 3 and 4 (RO–) had bone involvement and were given systemic chemotherapy for a prolonged duration. Unluckily, Case 3 had a recurrence 2 years later, while Case 4’s recurrence happened nearly one year later, and diabetes insipidus one and a half years later. They both survived and are still in remission. Conclusion—MS-LCH infants with a low age of the first presentation in the skin are prone to dissemination, while RO+ is associated with high mortality. In addition, bone involvement may be a protective factor. Immunohistochemical examination of skin tissue facilitates correct early diagnosis, and adequate follow-up is necessary.

Vascular inflammation is directly responsible for atherosclerosis. 5,2′-Dibromo-2,4′,5′-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV-vis absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.

Two different types of 2D nanosheets, including hydrophobic graphene (GR) and hydrophilic graphene oxide (GO), were filled into poly (vinyl alcohol) (PVA) polymers to prepare mixed matrix membranes (MMMs) for ethanol dehydration via pervaporation. The relationship between the physical/chemical properties of graphene and pervaporation performance of MMMs was investigated by a comparison of GR/PVA and GO/PVA MMMs in microstructure and PV performance. The incorporation of GO nanosheets into PVA reduced PVA crystallinity and enhanced the membrane hydrophilicity, while the incorporation of GR into PVA led to the opposite results. The incorporation of GR/GO into PVA depressed the PVA membrane swelling degree, and the incorporation of GR showed a more obvious depression effect. GR/PVA MMMs showed a much higher separation factor than GO/PVA MMMs, while they exhibited a much lower permeation flux than GO/PVA MMMs and pristine PVA membranes. The huge difference in microstructure and performance between GO/PVA and GR/PVA MMMs was strongly associated with the oxygen-containing groups on graphene lamellae. The higher permeation flux of GO/PVA MMMs was ascribed to the facilitated transport of water molecules induced by oxygen-containing groups and exclusive channels provided by GO lamellae, while the much lower permeation flux and higher separation factor GR/PVA MMMs was resulted from the smaller GR interplanar spacing (0.33 nm) and hydrophobicity as well as barrier effect of GR lamellae on the sorption and diffusion of water molecules. It was presumed that graphene intercalated with an appropriate number of oxygen-containing groups might be a good choice to prepare PVA-based MMMs for ethanol dehydration, which would combine the advantages of GR’s high interlayer diffusion selectivity and GO’s high permeation properties. The investigation might open a door to achieve both of high permeation flux and separation factor of PVA-based MMMs by tuning the microstructure of graphene.

Introduction: Combination of trastuzumab (T) and lapatinib (L) has been showed to significantly improve the prognosis of HER2+ heavily pretreated metastatic breast cancer (MBC). Whether TL combined chemotherapy (TLC) can further improve the efficacy in HER2+ MBC remains to be further studied. The aim of the study was to report the first real-world data of TLC in HER2+ MBC, including the efficacy, safety and treatment patterns.Methods: Patients with HER2+ MBC treated with TLC in 5 institutions of China from September 2013 to July 2019 were included. Progression free survival (PFS), objective response rate (ORR), overall survival (OS), toxicity profile and treatment pattern were reported.Results: A total of 285 patients were included. 88.8% were exposed to trastuzumab and 49.2% received 2 or more lines of systematic therapy before TLC previously. The most common chemotherapy regimens combined with TL were capecitabine (40.7%) and vinorelbine (21.4%) and almost 1/3 received maintenance treatment after TLC. Median PFS was 10.9 months while patients received TLC as first line treatment showed longest median PFS of 20.7 months. Patients pretreated with trastuzumab showed a median PFS of 10.2 months. In patients who pretreated with trastuzumab, the continuation of trastuzumab on the basis of standard lapatinib plus capecitabine had a median PFS of 11.3 months. TL combined with capecitabine or vinorelbine showed no significant difference in median PFS, though TL combined with capecitabine had numerically prolongation (11.4 vs. 8.5 months, p = 0.231). Patients had brain metastasis (BM) also showed a median PFS (intracranial and extracranial lesions considered) of 10.6 months. Lines of systematic metastatic treatment was an independent predictive factor of PFS. The median OS was not reached. Two hundred and seventy seven patients were included in ORR analysis. ORR was 42.6%. Toxicities of triplet combinations were tolerable and the most common grade 3 and 4 adverse events were neutropenia (16.8%).Conclusions: TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice.Clinical Trial Registration:ClinicalTrials.gov, Identifier: NCT04001634.

In this study, we investigated the effects of solid lipid nanoparticle (SLN) nanocrystallization on the stability of two fractions of oat globulin-derived peptides. i.e., OGL, with molecular weight (MW)