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The vast majority of high-performance perovskite solar cells (PSCs) are based on a formamidinium lead iodide (FAPbI3)-dominant composition. Nevertheless, the FA-based perovskite films suffer from undesirable phase transition and defects-induced non-ideal interfacial recombination, which significantly induces energy loss and hinders the improvement of device performance. Herein, we employed 4-fluorophenylmethylammonium iodide (F-PMAI) to modulate surface structure and energy level alignment of the FA-based perovskite films. The superior optoelectronic films were obtained with reduced trap density, pure α-phase FAPbI3 and favorable energy band bending. The lifetime of photogenerated charge carriers increased from 489.3 ns to 1010.6 ns, and a more “p-type” perovskite film was obtained by the post-treatment with F-PMAI. Following this strategy, we demonstrated an improved power conversion efficiency of 22.59% for the FA-based PSCs with an open-circuit voltage loss of 399 mV.

Hole transporting materials (HTMs) play an unparalleled role in heightening the stability and photovoltaic performance of perovskite solar cells (PSCs). The organic small molecule spiro-OMeTAD is frequently utilized for HTM in PSCs. However, the raw spiro-OMeTAD without dopant would be harmful to the development of highly efficient PSCs, due to its unsatisfied hole mobility and conductivity. Therefore, we introduce an inorganic dopant (chromium trioxide, CrO3) into the lithium-salt doped spiro-OMeTAD. Because of the exclamatory oxidizability of CrO3, it can accelerate the oxidation of spiro-OMeTAD and thereby enhancing the hole mobility of HTM. The introduction of CrO3 not only substantially decreases the density of defects, but also adjusts spiro-OMeTAD energy band, and thus effectively suppresses the hysteresis and improving stability of PSCs. In the end, we obtained a power conversion efficiency (PCE) as high as 22.6% after doping CrO3 in spiro-OMeTAD. The facile, low cost and outstanding photovoltaic performance render CrO3 an excellent dopant for HTMs in PSCs.

Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma (HCC) in individuals infected with the hepatitis virus. However, the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined. Here, we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1 (AFB1) targets. Among the most significant hits was the aryl hydrocarbon receptor (AHR), a ligand-binding transcription factor regulating cell metabolism, differentiation, and immunity. AHR-deficient cells tolerated high concentrations of AFB1, in which AFB1 adduct formation was significantly decreased. AFB1 triggered AHR nuclear translocation by directly binding to its N-terminus. Furthermore, AHR mediated the expression of P450 induced by AFB1. AHR expression was also elevated in primary tumor sections obtained from AFB1-HCC patients, which paralleled the upregulation of PD-L1, a clinically relevant immune regulator. Finally, anti-PD-L1 therapy exhibited greater efficacy in HCC xenografts derived from cells with ectopic expression of AHR. These results demonstrated that AHR was required for the AFB1 toxicity associated with HCC, and implicate the immunosuppressive regimen of anti-PD-L1 as a therapeutic option for the treatment of AFB1-associated HCCs.

Hypoxia, the most common feature in the tumor microenvironment, is closely related to tumor malignant progression and poor patient’s prognosis. Exosomes, initially recognized as cellular “garbage dumpsters”, are now known to be important mediums for mediating cellular communication in tumor microenvironment. However, the mechanisms of hypoxic tumor cell-derived exosomes facilitate colorectal cancer progression still need further exploration. In the present study, we found that exosomes from hypoxic colorectal cancer cells (H-Exos) promoted G1-S cycle transition and proliferation while preventing the apoptosis of colorectal cancer cells by transmitting miR-210-3p to normoxic tumor cells. Mechanistic investigation indicated that miR-210-3p from H-Exos elicited its protumoral effect via suppressing CELF2 expression. A preclinical study further confirmed that H-Exos could promote tumorigenesis in vivo. Clinically, the expression of miR-210-3p in circulating plasma exosomes was markedly upregulated in colorectal cancer patients, which were closely associated with multiple unfavorable clinicopathological features. Taken together, these results suggest that hypoxia may stimulate colorectal cancer cells to secrete miR-210-3p-enriched exosomes in tumor microenvironment, which elicit protumoral effects by inhibiting CELF2 expression. These findings provide new insights on the mechanism of colorectal cancer progression and potential therapeutic targets for colorectal cancer.

Aims/Introduction This study aimed to evaluate the association between time in range (TIR) obtained from continuous glucose monitoring and the prevalence and degree of painful diabetic neuropathy. Materials and Methods A total of 364 individuals with diabetic peripheral neuropathy were enrolled in this study. Sensor‐based flash glucose monitoring systems were used to monitor the participants’ glucose levels, and the glycemic variability metrics were calculated, including the TIR, glucose coefficient of variation, standard deviation and the mean amplitude of glycemic excursions. The participants were asked to record any form of pain during the 2 weeks of monitoring, and score the pain every day on a numerical rating scale. Based on the numerical rating scale, the patients were divided into the pain‐free group, mild pain group and moderate/severe pain group. Results Overall, 51.92% (189/364) of the participants were diagnosed with painful diabetic neuropathy. Compared with the pain‐free group, the level of TIR decreased significantly in the mild pain and moderate/severe pain groups (P, Time in range is correlated with the degree of painful diabetic neuropathy independently of the glycated hemoglobin level, other glycemic variability metrics and risk factors among diabetes patients. Furthermore, time in range was a valuable clinical evaluation indicator for patients with diabetes.

Yiran Si,1 Jian Yue,2 Zhaoyang Liu,3 Mo Li,3 Feng Du,4 Xue Wang,2 Zhong Dai,5 Nanlin Hu,1 Jie Ju,1 Songlin Gao,1 Xiaobing Wang,3 Peng Yuan2 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 4China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIPII Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, 100142, People’s Republic of China; 5Department of Medical Oncology, Cancer Hospital of Huanxing Chaoyang District, Beijing, 100005, People’s Republic of ChinaCorrespondence: Peng YuanDepartment of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, #17 Pan Jia Yuan Nan Li, Chao Yang District, Beijing, 100021, People’s Republic of ChinaTel +86 10-87787245Email yuanpeng01@hotmail.comXiaobing WangState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, #17 Pan Jia Yuan Nan Li, Chao Yang District, Beijing, 100021, People’s Republic of ChinaTel +86 10-87788430Email wangxb@cicams.ac.cnPurpose: Immunologically quiescent of breast cancer cells has been recognized as the key impediment for the breast cancer immunotherapy. In this study, we aimed to investigate the role of nanoparticle-mediated sonodynamic therapy (SDT) in promoting anti-tumor immune of breast cancer cells and its potential immune mechanisms.Materials and Methods: The phase-transformation nanoparticles (LIP-PFH nanoparticles) were in-house prepared and its physiochemical characters were detected. The CCK-8 assay, apoptosis analysis and Balb/c tumor model establishment were used to explore the anti-tumor effect of LIP-PFH nanoparticles triggered by low-intensity focused ultrasound (LIFU) both in vitro and in vivo. Flow cytometry and immunohistochemistry of CD4+T, CD8+T, CD8+PD-1+T in blood, spleen and tumor tissue were performed to represent the change of immune response. Detection of immunogenic cell death (ICD) markers was examined to study the potential mechanisms.Results: LIP-PFH nanoparticles triggered by LIFU could inhibit the proliferation and promote the apoptosis of 4T1 cells both in vitro and in vivo. CD4+T and CD8+T cell subsets were significantly increased in blood, spleen and tumor tissue, meanwhile CD8+PD-1+T cells were reduced, indicating enhancement of anti-tumor immune response of breast cancer cells in the nanoparticle-mediated SDT group. Detection of ICD markers (ATP, high-mobility group box B1, and calreticulin) and flow cytometric analysis of dendritic cell (DC) maturity further showed that the nanoparticle-mediated SDT can promote DC maturation to increase the proportion of cytotoxic T cells by inducing ICD of breast cancer cells.Conclusion: The therapy of nanoparticles-mediated SDT can effectively enhance anti-tumor immune response of breast cancer.Keywords: breast cancer, immune response, phase-transformation nanoparticles, immunogenic cell death, DC maturation

Regardless of the impressive progress that perovskite solar cells (PSCs) have achieved, especially considering their power conversion efficiency (PCE) over 25%, traditional PSCs still contend with an inherent instability with exposure to humidity, which remains as a critical issue for the realization of commercial production. Herein, we proposed an effective pathway to relieve the instability of PSCs without sacrificing efficiency by introducing a 2D phase at the surface of the 3D perovskite film, based on a novel organic cyclohexylmethylammonium iodide (CMAI). The self-assembled thin 2D capping layer atop the 3D perovskite layer can not only reduce the ionic defects, but also serve as a protective barrier against moisture. Consequently, the champion device incorporating 2D perovskite capping layers delivered an open-circuit voltage (Voc) of 1.19 V, which contributes to an impressive PCE of 22.06% on account of the improved charge extraction and decreased non-radiative recombination. More importantly, an excellent long-term stability along with mitigated hysteresis was observed for the modified devices as a result of the suppressed ion migration and high humidity resistance of the 2D perovskite film. Our finding provides a comprehensive approach for simultaneously enhancing the efficiency and stability of PSCs through dimension engineering utilizing CMA-based 2D perovskite materials.

The influence of the wing-tip vortex of leading aircraft on energy savings, quantified by formation aerodynamic force fraction of the following aircraft, is studied at transonic speed for a matrix of leading aircraft’s vortex locations. The research model adopts the hybrid formation of medium and large aircraft. The leading aircraft is scaled by 2.1%, and the following aircraft is scaled by 1.4%. An aerodynamic benefit “map” is developed to determine the optimum location of the following aircraft relative to the leading aircraft wake and to compare with experimental results, thus validating the use of CFD for the formation flight at cruising speed. The response surface model of aerodynamic gain effect relative to formation parameters is established via numerical calculation and wind tunnel test. The optimal formation parameters and the setting criteria of the study model are optimized. Results show that the wing-tip vortex of large aircraft significantly increases lift and reduces drag on the medium-sized aircraft following it. Reduced drag slightly increases with the flow direction position. With the increase of flow direction distance, the peak area moves from 15% of wing-tip overlap to 20% of overlap. In addition, the maximum drag decreases about 16%, and the maximum lift increases about 12%. The lift drag ratio of the optimal position is increased by 27%, which is twice as large as that of the same scale ratio aircraft formation. Results show that the increase of lift is mainly caused by the increase of suction peak and suction range.

This article examines the impact of farmers’ perceptions of temperature change on implementing environmentally friendly agriculture practices on rubber plantations. Based on the data collected from 611 smallholder rubber farmers in Xishuangbanna Dai Autonomous Prefecture (XSBN) in the upper Mekong region, an endogenous switching probit model and an endogenous treatment effects model are applied to estimate the impacts of farmers’ perceptions of temperature change on implementing environmentally friendly rubber plantations (EFRP) proxied by the intercropping system. While the real annual average temperature in XSBN has been increasing, only 59% of respondents perceived an increasing trend, whereas over 38% perceived no change. Farmers’ perceptions of temperature change appear to hinge on their education and socioeconomic characteristics and the experience of shocks related to regional climate change. Improving farmers’ perceptions of increasing temperature can significantly foster their practice of EFRP. Hence, policies that promote awareness of regional climate change can effectively encourage the implementation of mitigation practices.

Relatively little is known about the association between Internet use and environmentally‐friendly agricultural innovation adoption. To fill this void, this study examines the impact of Internet use on the adoption of sustainable agricultural practices (SAPs) and their heterogeneous effects on farm income and household income. Unlike previous studies that analyse the dichotomous decision of agricultural innovation adoption, this study captures the number of SAPs adopted. We apply both endogenous‐treatment Poisson regression model and unconditional quantile regression model to analyse unique farm‐level data collected from China. The empirical results show that Internet use exerts a positive and statistically significant impact on the number of SAPs adopted, and the joint effects of Internet use and SAP adoption on farm income and household income are heterogeneous. In particular, we show that Internet use has a larger impact at the upper tail of household income but it has no significant impact on farm income. SAP adoption is negatively associated with farm income and household income across the selected quantiles.

Idiopathic Pulmonary fibrosis(PF)is a chronic progressive disease, which is a lack of effective treatment,and the pathogenesis of IPF is not fully elucidated. Asiaticoside(AS) is isolated from Centella asiatica and has the effect of promoting scar healing and reducing scar formation. However,its possible role in idiopathic pulmonary fibrosis remains unclear. Adenosine A2A receptor (A2AR) is reported a protective factor in pulmonary fibrosis, and the bone morphogenetic protein 7 (BMP7) signaling pathway plays a crucial role in fibrosis in multiple organs. But the impact of A2AR on the BMP7 pathway has not yet been reported. Therefore, we hypothesized AS may promote the expression of A2AR, and then influence the BMP7/Smad1/5 pathway to alleviate pulmonary fibrosis. A2AR−/− mice and wild-type (WT) mice were administered bleomycin (BLM) by intratracheal injection. AS (50 mg/kg/d) was given daily for 28 days. AS reduced collagen deposition in lung tissue, interstitial lung inflammation. Furthermore, AS promoted A2AR expression and BMP7 pathway. Collectively, AS may attenuate BLM-induced pulmonary fibrosis by upregulating the BMP7 signaling pathway through A2AR.

Expression and diagnostic value of serum toll-like receptor-4 (TLR-4), Toll-like receptor-5 (TLR-5) and interferon regulatory factor 4 (IRF4) in middle-aged and elderly patients with knee osteoarthritis (KOA) and their correlation with Interleukin 1β (IL-1β), interleukin-6 (IL-6), matrix metalloproteinase-1 and tumor necrosis factor-α (TNF-α) were investigated. Sixty-eight middle-aged and elderly patients with KOA in Puyang Hospital of Traditional Chinese Medicine were selected as the study group and 49 healthy people receiving physical examination were the control group. Levels of serum TLR-4, TLR-5, IRF4, IL-1β, IL-6, MMP-1 and TNF-α were measured by enzyme linked immunosorbent assay (ELISA). Correlation between the expression levels of serum TLR-4, TLR-5, IRF4 and K-L grades was determined by Spearman correlation analysis. The diagnostic efficacy of serum TLR-4, TLR-5 and IRF4 for KOA was analyzed by the receiver operator characteristics analysis (ROC). Expression of serum TLR-4, TLR-5 and IRF4 in the study group was significantly higher than those in the control group. The sensitivity and specificity of TLR-4 in the diagnosis of KOA were, respectively, 76.47 and 93.88%, those of TLR-5 were 73.29 and 87.76%, those of IRF4 were 72.06 and 95.92%, and those of TLR-4, TLR-5 and IRF4 were 94.12 and 97.96%. Expression of serum TLR-4, TLR-5 and IRF4 was significantly higher in the severe group than in the moderate group, and significantly higher in the moderate group than those the in mild group, and significantly higher in the mild group than those in the suspected mild group. Expression of TLR-4, TLR-5 and IRF4 in serum was positively correlated with the concentration of IL-1β, IL-6, MMP-1 and TNF-α, respectively (P

Objectives This study aims to characterize the expression profiles of circRNAs in primary Sjogren’s Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS. Methods We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS. Results Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes. Conclusion This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS.

Titania (TiO2) has wide applications in the realm of perovskite solar cells (PSCs). Because high-temperature processing severely limits the application of flexible and tandem devices, it is signifi...

Major salivary gland ultrasonography (SGUS) is increasingly being recognized as having critical roles in differentiating primary Sjögren’s syndrome (pSS) from other connective tissue disorders. Contrast-enhanced ultrasonography (CEUS) has been reported to evaluate microvascularity of lesions in different tissues with objective angiographic index, eliminating the observer-dependent defect of ultrasonography. However, there are few relevant studies concentrating on the application of CEUS in the diagnosis and assessment for pSS, and their clinical utility prospect remains uncertain. In this study, a total of 227 eligible patients were enrolled, including 161 pSS and 66 non-pSS patients with comprehensive ultrasonographic evaluation of the parotid and submandibular glands, including grayscale ultrasonography, color Doppler sonography (CDS), and CEUS. Compared with non-pSS, pSS patients had significantly higher grayscale ultrasound (US) scores and CDS blood grades in the parotid gland and significantly higher grayscale US and CEUS scores in the submandibular glands. Diagnostic model combining ultrasonographic signatures, anti-SSA/Ro60, and keratoconjunctivitis sicca (KCS) tests showed a remarkable discrimination [mean area under the curve (AUC)0.963 in submandibular glands and 0.934 in parotid glands] for pSS, and the nomogram provided excellent prediction accuracy and good calibration in individualized prediction of pSS. A combination of multiple ultrasonographical examinations of the major salivary glands (SGs) is a promising technique that may be used as a practical alternative to minor SG biopsy in the detection of pSS.

This paper provides a review of the NTIRE 2021 challenge targeting defocus deblurring using dual-pixel (DP) data. The goal of this single-track challenge was to reduce spatially varying defocus blur present in images captured with a shallow depth of field. The images used in this challenge were obtained using a DP sensor that provided a pair of DP views per captured image. Submitted solutions were evaluated using conventional signal processing metrics, namely peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Out of 185 registered participants, nine teams provided methods and competed in the final stage. The paper describes the methods proposed by the participating teams and their results. The winning teams represent the state-of-the-art in terms of defocus de-blurring using DP images.

ObjectiveWe sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.MethodsPRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI.ResultsIn people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively.ConclusionsPRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Echocardiographic detection of abnormalities occurring medially and distally in coronary arteries is uncommon and is not well recognized. Herein, we describe an 87-year-old woman with two distinct aneurysms involving a branch of the left anterior descending coronary artery (LAD), one of which communicated with the pulmonary artery (PA). Initially determined via transthoracic echocardiography (TTE), these findings were subsequently validated by coronary computed tomography angiography (CTA). We also present a review of the published studies of multiple coronary artery aneurysms (CAAs) exceeding 20 mm in diameter, focusing on the location, etiology, symptoms, and common ultrasonic characteristics of 30 cases. Echocardiography is a valuable, noninvasive technique for initial detection, monitoring, and follow-up of CAAs, serving to direct further diagnostics.

The harmful trace elements will be released during coal utilization, which can cause environment pollution and further endangering human health, especially for heavy metal elements. Compared to combustion, the release of heavy metal elements during coal pyrolysis process, as a critical initial reaction stage of combustion, has not received sufficient attention. In the present paper, a low rank coal, from Xinjiang province in China, was pyrolyzed in a fixed bed reactor from room temperature, at atmospheric pressure, with the heating rate of 10 °C/min, and the final pyrolysis temperature was from 400 to 800 °C with the interval of 100 °C. The volatility of heavy metal elements (including As, Hg, Cd and Pb) during pyrolysis process was investigated. The results showed the volatility of all heavy metal elements increased obviously with increasing temperature, and followed the sequence as Hg > Cd > As > Pb, which was mainly caused by their thermodynamic property and occurrence modes in coal. The occurrence modes of heavy metals were studied by sink-and-float test and sequential chemical extraction procedure, and it can be found that the heavy metal elements were mainly in the organic and residual states (clay minerals) in the raw coal. And most of the organic heavy metals escaped during the pyrolysis process, the remaining elements were mainly in the residual state, and the elements in Fe–Mn state also tended to remain in the char.

Hole-transport layer (HTL) plays a crucial role in the photovoltaic performance of perovskite solar cells (PSCs). In order to improve the function property of HTLs, we first use potassium permanganate (KMnO4) as a dopant for the oxidization of 2,2′,7,7′-tetrakis(N,N-p-dimethoxyphenylamino)-9,9′-spirobifluorene (spiro-OMeTAD). The reaction between KMnO4 and spiro-OMeTAD produces the oxidized-state spiro-OMeTAD, which enhances the conductivity and adjusts the energy level of HTL. The dual functions of KMnO4 dopant bring high photovoltaic performance of the devices. The planar PSC based on photoactive layer of mixed-cation–anion perovskite and hole-transport layer of spiro-OMeTAD doped with 1.0 mol % KMnO4 achieves a power conversion efficiency of 20.03%. Meanwhile, the hysteresis effect of the device is greatly suppressed. The simple and low-cost processing and significant performance improvement render this method promising.

This paper estimates the shadow price of CO2 from burning maize straw in the Chinese agricultural sector and explores the related policy implications for decision makers. Using a quadratic directional distance function, we evaluate the production inefficiency and shadow prices of CO2 reduction for the seven major maize-producing provinces in China for 1996–2014. In general, the efficiency improves over time. Shandong province ranked as the top one with full efficiency considering both economic and environmental impacts as of 2014. The mean shadow price for the CO2 emission was 0.45 yuan/kg (US$75/t), whereas the province-specific shadow prices varied within the interval bounded by 0 and 0.913 yuan/ha (US$152/t). The marginal abatement cost curve was downward-sloped and indicated the need for curbing CO2 emission in areas exhibiting the highest pollution rates. Given the marginal abatement cost patterns, the transaction costs associated with implementation of the conservation practices (tillage) should not exceed 335 yuan/ha in order to ensure the welfare gains. This government-provided payment would compensate farmers for yield reductions in favor of implementing conservation practices that would substantially reduce CO2 emissions.

Sepsis is a major cause of patient mortality and morbidity from bacterial infections. Although neutrophils are known to be important in the development of sepsis, how distinctive neutrophil subtypes regulate inflammatory processes involved in septicemia remains unclear. Preconditioning protects organisms against subsequent higher-dose exposures to the same, or even different, stimuli. Several studies have reported various effects of preconditioning on immune cells. However, the detailed mechanisms underlying neutrophil-mediated protection through preconditioning in sepsis remain unknown. Methods: Flow cytometry was conducted to sort the mice peritoneal lavage cells and the blood samples from patients with sepsis. Western blotting and ELISA were carried out to elucidate the expression of TLR9 signal transduction pathway proteins. Histological analysis was used to assess the effect of InP on intestine and liver structure in tlr9-/- and cav-1-/- mice. Fluorescence microscopy, Co-IP, and FRET were carried out to determine the association of TLR9 with Cav-1. Results: We show that membrane toll-like receptor-9 positive (mTLR9+) neutrophils exert a protective effect against fatal bacterial infections through the process of inflammatory preconditioning (InP). InP, which occurs in the setting of a low-dose bacterial challenge, active ingredient is Monophosphoryl lipid A (MPLA), triggers the membrane translocation of TLR9 from the neutrophil cytosol, where it binds to Cav-1. Our findings showed that InP enables TLR9 to facilitate MyD88-mediated TRAF3 and IRF3 signal transduction. Depletion of either TLR9 or Cav-1 largely eliminates the neutrophil-mediated InP effect in sepsis models in vitro and in vivo. Further, examination of clinical samples from patients with sepsis showed that clinical outcomes and likelihood of recovery are closely correlated with mTLR9 and Cav-1 expression in circulating neutrophils. Conclusion: These results demonstrate that the TLR9-Cav-1 axis is a critical signaling pathway involved in the regulation of neutrophil-dependent MPLA mediated InP, and the presence of mTLR9+ neutrophils could be an attractive indicator of clinical outcomes in bacterial sepsis that could be further explored as a potential therapeutic target.

In this letter, we explore the detection of people with camouflage pattern in cluttered natural scenes. First, considering the lack of open evaluation and training data on camouflaged people detection, a specific dataset of camouflaged people in natural scenes is constructed by us for the first time to the best of our knowledge. Secon, due to the serious corruption of the discrimination of low-level features by the camouflage patterns and cluttered background, we extract the high-level semantic features in deep convolution network and introduce short connections in deconvolution phase, to construct the dense deconvolution network. In training procedure, we augment and shift the images of camouflaged people to generate the proper training data. Attributing to the usage and fusion of semantic information, the proposed network effectively labels the camouflaged people regions as a whole. Finally, we use the superpixel segmentation and spatial smoothness constraint for further improvement of the detection result. Experimental results demonstrate that the proposed method outperforms the classical camouflaged object detection method and typical CNN-based detection methods.

This study examines the impacts of sunk costs and path dependency of rubber farming on farmers’ production responses to expected changes in the price of rubber based on a simple choice experiment implemented in the upper Mekong region in March, 2013. The results show that nearly 73% of farmers choose to adjust their production behaviors when the price of rubber is hypothesized to increase by 50%, while only approximately 55% choose to adjust their behaviors when the price of rubber is hypothesized to decrease by 50%. The responses of farmers to these two hypothetical changes in the price of rubber are significantly asymmetric. The estimation results of empirical models consistently indicate that higher sunk costs and a longer path dependency of rubber farming significantly hinder the probability that smallholders will adjust their production behaviors in response to the two hypothetical changes in the price of rubber. The significant difference in the impacts of sunk costs and path dependency on the choice of response behaviors under the two hypothetical situations may, to some extent, help explain the observed asymmetric responses. Additionally, the impacts of sunk costs and path dependency on the specific adjustments to production behaviors are heterogeneous. The findings provide essential empirical evidences for the roles of sunk costs and path dependency in farmers' production behaviors in the context of the price volatility of agricultural products.

Objective To investigate distinct features of renal involvement in patients with primary Sjögren’s syndrome (pSS) and to identify potential factors associated with renal involvement. Methods Four hundred and thrity‐four pSS patients from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2017 were included in a cross‐sectional study. Patients with renal involvement were compared with their age‐ and gender‐matched controls (pSS without renal involvement). Demographic, clinical, histological, nephritic, immunological features of renal involvement in pSS were systematically analyzed. Possible factors related to renal involvement were identified using multivariate logistic regression analyses. Results One hundred and ninety‐two pSS patients (88.48%) with renal involvement were women with mean age of nearly 58 years and mean disease duration of above 4 years. Clinical manifestation, serologic and immunological features and renal biopsy class of the pSS patients with renal involvement were presented. By multivariate analyses, xerophthalmia, histological positivity for lower salivary gland biopsy (LSGB), anti‐SSA/Ro52‐positive, reduced complement 3 (C3) levels, hypoalbuminemia and anemia retained significant association with renal involvement in pSS (all P

To translate the English version of general medication adherence scale (GMAS) into a Chinese version and test its reliability and validity in Chinese patients with chronic diseases.After translating the original English version into Chinese (GMAS-C) following the forward-backward translation and expert review procedure, we conducted a pilot study among 10 chronic disease patients. Each patient took about 10 min to complete the scale and was asked about the difficulty of understanding or filling the scale. Then a total of 312 patients aged 18 years or older with chronic illness were selected from the outpatient departments of two tertiary hospitals and a community center in Tianjin from April 2019 to May 2020 by convenience sampling. Cronbach's α coefficient, item-total correlation and test-retest reliability were used to evaluate the scale reliability; expert evaluation method was used to evaluate the content validity of the scale; and exploratory factor analysis, confirmatory factor analysis, and known group validity were used to evaluate the construct validity of the scale.As a result of the adaptation process, the GMAS-C's structure was determined. It included 3 dimensions and 11 items and was reliable and valid for Chinese patients with chronic diseases. Total Cronbach's α coefficient of the scale was 0.781 and test-retest reliability coefficient was 0.883 after two weeks. The item-level content validity indexes (CVIs) were ≥ 0.78 for all items. A Kaiser-Meyer-Olkin test and Bartlett' test of sphericity test indicated that the sample met the requirements of factor analysis. Exploratory factor analysis extracted three factors with eigenvalue1, and 60% of the total variance was explained by three-factor solution. Confirmatory factor analysis showed acceptable fit indices (The GMAS-C demonstrates satisfactory reliability and validity. This scale can be a clinically useful tool to identify the levels of medication adherence and possible barriers for adherence of the medication regime in patients with chronic diseases.

The induction of inflammation and cytokine storm was proposed to play a critical role in COVID-19. This study is aimed at investigating the relationship between glucose metabolism and the inflammatory state of inpatients with COVID-19. 71 inpatients with COVID-19 were classified into nondiabetes mellitus (NDM) group, impaired fasting glucose (IFG) group, and diabetes mellitus (DM) group. The average hospitalization days were significantly shorter in DM patients when compared with patients in the IFG group and NDM group. CD4+ T cell percentage was higher while CD8+ T cells percentage was lower in the DM group than those in the NDM group. The serum levels of IL-6, IL-2, IL-10, and INF-γ in the DM group were upregulated when compared with those in the NDM group. The serum levels of TNF-α, IL-4, IL-2, IL-10, and INF-γ were significantly higher in the DM group than those in the IFG group. A significant difference was observed in CD4+ T cell, CD4+/CD8+ ratio percentage, IL-6, and IL-10 between the NDM group and DM group with adjusted BMI. In conclusion, COVID-19 patients with elevated glucose levels have promoted cytokine profiles and immune response.

With the rapid development and wide application of artificial neural networks, formal modeling and verification of their security become more and more significant. As a basic step towards the direction, this work proposes a comprehensive modeling framework for back propagation (BP) neural networks based on the formal language MSVL. In this framework, the structure and behavior of a BP neural network are formalized as specifications of data structures and operations, and they are in turn implemented as MSVL structs and functions, respectively. Based on the formalization, models of BP neural networks can be constructed and trained according to the requirements of users. Experimental results show that these models have good performance in terms of metrics concerning training and prediction such as loss and accuracy.

Aims Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes and is associated with adipokines. The C1q tumor necrosis factor‐related protein 9 (CTRP9) is a newly discovered adipokine. This study aimed to evaluate the association of serum CTRP9 levels with the prevalence and severity of CAN in patients with type 2 diabetes mellitus. Materials and Methods We enrolled 262 patients (aged ≥18 years) with type 2 diabetes mellitus into this study. Standard cardiovascular autonomic reflex tests (CARTs) were used to assess CAN and patients were divided into three groups accordingly: a non‐CAN group, an early CAN group, and a definite CAN group. Serum CTRP9 levels were measured by enzyme‐linked immunosorbent assay, and the tertiles were calculated. Results Serum CTRP9 levels decreased significantly in the early CAN and definite CAN groups (P, We evaluated the association between CTRP9 levels and the prevalence and severity of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus. We found that serum levels of CTRP9 were reduced significantly in CAN patients with type 2 diabetes mellitus. Further, we found that decreased serum CTRP9 levels significantly correlated with an increased prevalence ratio of CAN. Moreover, after adjusting for other risk factors, decreased serum CTRP9 levels were associated with an increased prevalence ratio of definite CAN.

The incidence of re-positive virus detection in patients who recovered from COVID-19 during quarantine was 6.2% in two designated locations, in Wuhan, indicating that suggestions for patients after discharge to be quarantined before leaving for home might be necessary. This experience might be referred to by other countries with epidemic outbreak.

Smart contract is a computer protocol running on the blockchain, which is widely used in various fields. However, its security problems continue to emerge. Therefore, it is necessary to audit the security of smart contract before it is deployed on the blockchain. Traditional testing methods cannot guarantee a high reliability and correctness required by the smart contract. This paper shows a method for using modeling, simulation and verification language (MSVL) and propositional projection temporal logic (PPTL) to model and verify the smart contract. First, a converter tool SOL2M which can convert Solidity program to MSVL program is developed. Then, the security properties of the smart contract are described by PPTL and a standardized process to verify the contract is designed through UMC4M (Unified Model Checker for MSVL). Finally, an example is given to illustrate the feasibility and practicability of this method in smart contract verification.

The behavior of entrepreneurs is significantly affected by the rules of the game and the behaviors of government officials, because they can affect the relative payoffs to different entrepreneurial activities. Based on a representative survey data of private firms and the information of city government officials in China, this paper shows that the change of key local government officials affects the time allocation of the entrepreneurs, and subsequently the performance of firms. In order to maintain and develop the business-government relationship, entrepreneurs have to allocate less time on productive activities and more time on non-productive activities. This effect is particularly large if 1) entrepreneurs do not have political connections, 2) new officials lack local working experience, 3) private firms belong to special industries, 4) private firms have large number of employees. This paper provides micro-level evidence to Baumol's entrepreneurship allocation theory and a mechanism to account for the observed negative effect of local government leadership turnover on local economic growth in China.

In recent years, the number of acute pancreatitis cases caused by hypertriglyceridemia has increased gradually, which has caught the attention of the medical community. However, because the exact mechanism of hypertriglyceridemic acute pancreatitis (HTG-AP) is not clear, treatment and prevention in clinical practice face enormous challenges. Animal models are useful for elucidating the pathogenesis of diseases and developing and testing novel interventions. Therefore, animal experiments have become the key research means for us to understand and treat this disease. We searched almost all HTG-AP animal models by collecting many studies and finally collated common animals such as rats, mice and included some rare animals that are not commonly used, summarizing the methods to model spontaneous pancreatitis and induce pancreatitis. We sorted them on the basis of three aspects, including the selection of different animals, analyzed the characteristics of different animals, different approaches to establish hypertriglyceridemic pancreatitis and their relative advantages and disadvantages, and introduced the applications of these models in studies of pathogenesis and drug therapy. We hope this review can provide relevant comparisons and analyses for researchers who intend to carry out animal experiments and will help researchers to select and establish more suitable animal experimental models according to their own experimental design.

Objectives To describe the clinical characteristics of patients in a Fangcang Hospital. Methods Non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests admitted between 7 February and 12 February 2020 to Dongxihu Fangcang Hospital, which was promptly constructed because of the rapid, exponential increase in COVID-19 patients in Wuhan, China, were included; clinical course through to 22 February was recorded. Results A total of 1012 non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests were included in the study. Thirty (of 1012, 3.0%) individuals were asymptomatic on admission. During hospitalization, 16 of 30 (53.3%) asymptomatic individuals developed different symptoms. Fourteen of 1012 patients (1.4%) remained asymptomatic from exposure to the end of follow up, with a median duration of 24 days (interquartile range 22–27). Fever (761 of 1012, 75.2%) and cough (531 of 1012, 52.4%) were the most common symptoms. Small patchy opacities (355 of 917, 38.7%) and ground-glass opacities (508 of 917, 55.4%) were common imaging manifestations in chest CT scans. One hundred patients (9.9%) were transferred to designated hospitals due to aggravation of illness. Diarrhoea emerged in 152 of 1012 patients (15.0%). Male, older age, diabetes, cardiovascular diseases, chills, dyspnoea, So2 value of ≤93%, white blood cell counts of >10 × 109/L and large consolidated opacities on CT images were all risk factors for aggravation of illness. Conclusions Non-critically ill individuals had different clinical characteristics from critically ill individuals. Asymptomatic infections only accounted for a small proportion of COVID-19. Although with a low incidence, diarrhoea was observed in patients with COVID-19, indicating the possibility of faecal–oral transmission.

Various methods of landmark reconstruction have been discussed in medical literature, but few describe defects involving the rim of the landmark. For landmark malposition, such as eyelid ectropion, borders are abnormally elongated by scar contracture. The reconstruction should thus restore both the cutaneous defect and the anatomical structure. We suggest the combination of local flaps via end-to-end connection and transposition for facial landmark reconstruction.Ten patients who had facial landmark malpositions caused by scar contractions, and 5 patients who had landmark defects, were successfully treated using this combination flap technique. Among the 15 patients, landmark malposition repairs of the nasal ala, nasal columella, eyelid margin, Cupid's bow, and eyebrow were performed.Most flaps survived without complications; one procedure resulted in the cutaneous tip developing necrosis, which was successfully healed within 2 weeks of conservative treatment. The landmark was reconstructed with aesthetics in mind, and no subsequent scar contracture was observed. After a 6- to 14-month follow-up period, successful landmark reconstruction had been achieved in all 15 patients via a single-stage procedure.A combination of local flaps is a viable option for facial landmark reconstruction in selected patients having landmark rim destruction.Diverses méthodes de reconstruction phares par repères anatomiques sont abordées dans les publications médicales, mais peu décrivent les anomalies touchant le pourtour des repères anatomiques. En cas de malposition de ces repères, telles que l’ectropion des paupières, les bordures sont anormalement prolongées par la contracture entourant les cicatrices. La reconstruction doit donc restaurer à la fois l’anomalie cutanée et la structure anatomique. Les chercheurs proposent de combiner des lambeaux locaux par des connexions de bout en bout et la transposition de la reconstruction des repères faciaux.Dix patients qui présentaient des malpositions des repères faciaux causées par une contracture cicatricielle et cinq patients qui présentaient des anomalies de ces repères ont été traités avec succès au moyen de la technique des lambeaux combinés. Parmi les 15 patients, les réparations des malpositions des repères des ailes du nez, de la columelle nasale, du bord des paupières, des ridules de la lèvre supérieure et des sourcils.La plupart des lambeaux ont survécu sans complications; une intervention s’est soldée par une nécrose de la pointe cutanée qui a guéri dans les deux semaines grâce à un traitement classique. Le repère a été reconstruit en tenant compte de l’esthétique, et aucune contracture cicatricielle subséquente ne s’est produite. Après une période de suivi de six à 14 mois, les 15 patients ont profité d’une reconstruction réussie des repères par une intervention en une étape.Une combinaison de lambeaux locaux est une option viable pour la reconstruction de repères faciaux chez certains patients présentant une destruction du pourtour des repères anatomiques.

Background The concept of perceived control reflects the belief that one has resources needed to cope with negative events and the ability to positively influence consequences of those negative events. In patients with heart failure, perceived control is associated with a variety of health outcomes. Perceived control is commonly measured using the Control Attitudes Scale-Revised (CASR). There is no Chinese version of the CAS-R (CCAS-R). Objective The purpose of this article was to perform linguistic validation and psychometric evaluation of the CCAS-R. Methods The CAS-R was translated into Chinese according to Brislin's model. Then, a multicenter observational study was performed. Floor and ceiling effects, internal consistency, structural validity, and hypothesis testing were all assessed for psychometric validation of the CCAS-R. Results A total of 227 patients with chronic heart failure were included. There were no ceiling or floor effects detected. Cronbach α was 0.94, indicating a high reliability. The results of the confirmatory factor analysis showed that the 1-factor structure as proposed by the original CAS-R fits the data well. The results of the principal component analysis suggested that the 1-factor structure was optimal as well, accounting for 71.6% of the total variance. The a priori hypothesis was supported by a statistically significant correlation between the CCAS-R and 3 theoretically related variables. Conclusion We developed a semantically equivalent version of the CAS-R in Chinese. The evaluation of the instruments' psychometric properties demonstrated that the CCAS-R has good reliability and validity for use in Chinese patients with chronic heart failure.

Both photodynamic therapy (PDT) and sonodynamic therapy (SDT) are fast growing activated therapies by using light or ultrasound to initiate catalytic reaction of sensitizing agents, showing great potentials in clinics because of high safety and non-invasiveness. Sensitizers are critical components in PDT and SDT. Sinoporphyrin sodium (DVDMS) is a newly identified sensitizer derived from Photofrin that has been approved by FDA. This review is based on previous articles that explore the applications of DVDMS mediated photodynamic/sonodynamic cancer therapy and antimicrobial chemotherapy. Researchers utilize different cell models, distinct treatment protocols to explore the enhanced therapeutic response of neoplastic lesion. Moreover, by designing a series of nanoparticles for loading DVDMS to improve the cellular uptake and anti-tumor efficacy of PDT/SDT, which integrates diagnostics into therapeutics for precision medical applications. During the sono/photo-activated process, the balance between oxidation and anti-oxidation, numerous signal transduction and cell death pathways are also involved. In addition, DVDMS mediated photodynamic antimicrobial chemotherapy (PACT) can effectively suppress bacteria and multidrug-resistant-bacteria proliferation, promote the healing of wounds in burn infection. In brief, these efficient preclinical studies indicate a good promise for DVDMS application in the activated sono-/phototherapy.

Background Genome-wide chromosomal instability, instead of specific somatic mutations or copy-number alterations in selected genes, is a significant property of cancer and may suggest a new strategy for treatment. Here we utilized cell-free DNA (cfDNA) sequencing to display the whole picture of chromosomal instability in patients with metastatic breast cancer (MBC), and evaluate its predictive value for patient survival. Methods The clinical data of 65 patients who had frozen plasma and planned to change the therapeutic regimen were retrospectively enrolled. Low-coverage whole-genome sequencing of cfDNA was performed to generate the chromosomal instability represented by chromosomal instability (CIN) score. Results Tumors with diverse status of hormone receptor and HER2 represented diverse chromosomal instability across the whole genome. According to the receiver operating characteristic curve and the statistical distribution, CIN score exceed 3881 was defined as “High”. 32 (53.3%) patients with high CIN score had similar clinicopathologic characteristics compared with low CIN score patients. The median overall survival of patients with high CIN score was 21.2 months (95% CI 14.1–28.3), which was significantly inferior to those with low CIN score (not reached, P = 0.006). Regardless of various treatment regimens, the median progression free survival in patients with high CIN score was 7.3 months, which was significantly worse than those in the low CIN score population (11.0 months, P = 0.034). Multivariate analysis revealed that CIN score was an independent prognostic factor, with hazard ratio of 3.563 (P = 0.005). Conclusions To our knowledge, this is the first study illustrating the prognostic value of chromosomal instability derived from cfDNA in MBC., Highlights • Novel UCAD pipeline to profile genome-wide chromosomal instability in cfDNA. • Genome-wide chromosomal instability is a robust independent prognostic biomarker. • HER2 amplification was successfully identified from cfDNA in our cohort.

Background: Since December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCP) occurred in Wuhan, and rapidly spread throughout China We aimed to clar

Due to extensive applications of deep learning and neural networks, their security has attracted more and more attentions from academic and industrial circles. Under the guidance of the theory of formal verification, this paper summarizes three basic problems which indicate the common features of different neural networks, and proposes three typical properties covering the correctness of a model, the correctness of a sample and the robustness of a model for neural network systems. The method is driven by these properties, the model is constructed using the MSVL language and the properties are characterized by the logic PPTL. On this basis, the modeling and verification process is done in the MC compiler.

Background Alzheimer's disease (AD) as the most common cause of dementia among older people has aroused the universal concern of the whole world. However, until now there is still none effective treatments. Consequently, the development of new drugs targeting this complicated brain disorder is urgent and needs more efforts. In this review, we detailed the current state of knowledge about new candidate drugs targeting the pathological proteins especially the drugs which are employed using the combined methods of in vitro and in silico. Methods We looked up and reviewed online papers related to the pathogenesis and new drugs development of AD. Then, articles up to the requirements were respectively analyzed and summaried to provide the latest knowledge about the pathogenic effect and the new candidate drugs targeting Aβ and Tau proteins. Results New candidate drugs targeting the Aβ include decreasing the production, promoting the clearence and preventing aggregation. However these drugs have mostly failed in Phase III clinical trial stage due to the unsuccessful of reversing cognition symptoms. As to tau protein, the prevention of tau aggregation and propagation is a promising strategy to synthesize/design mechanismbased drugs against tauopathies. Some candidate drugs are under research. Moreover, because of the complex pathogenesis of AD, multi-target drugs have also shed light on the treatment of AD. Conclusion Given to the consecutive failure of Aβ-directed drugs and the feasibilities of tautargeted therapy, more and more researchers suggested that the AD treatment should be moved from Aβ to tau or focused on considering the soluble form of Aβ and tau as a whole. Moreover, the novel in silico methods also have great potential in drug discovery, drug repositioning, virtual screening of chemical libraries. No matter how many difficulties and challenges in prevention and treatment of AD, we firmly believe that the effective and safe drugs will be found using the combined methods in the immediate future with the global effort.

Inhibition of the increased aerobic glycolysis in cancer cells is a promising methodology for various malignant tumor therapies but is limited by systemic toxicity, at least in part. Recent studies suggest that dual restriction of glycolysis and mitochondrial function may overcome this issue. Sonodynamic therapy (SDT), a prospective therapeutic modality for cancers, has been reported to induce mitochondria-dependent cell damage. Here, we investigated the combined effect of SDT and 2-deoxyglucose (2DG), an anti-glycolytic agent, on breast cancer both in vitro and in vivo. In vitro, we found that, compared with a single treatment, SDT + 2DG co-treatment significantly decreased cell viability and increased cell apoptosis. Moreover, the generation of reactive oxygen species was enhanced and mitochondrial membrane potential (MMP) was reduced after SDT + 2DG co-treatment. Furthermore, the oxidative phosphorylation was also restrained after SDT + 2DG co-treatment, further to cause the blockage of ATP provision. In vivo, SDT + 2DG markedly reduced tumor volume and weight, consistent with the in vitro findings. Furthermore, toxicology tests concurrently indicated that the dosages of sinoporphyrin sodium and 2DG were comparatively tolerable. Generally, these results indicated that SDT + 2DG combination therapy may be an available, promising therapy for highly metastatic breast cancer.

Sub-wavelength antireflection moth-eye structures were fabricated with Nickel mold using Roll-to-Plate (R2P) ultraviolet nanoimprint lithography (UV-NIL) on transparent polycarbonate (PC) substrates. Samples with well replicated patterns established an average reflection of 1.21% in the visible light range, 380 to 760 nm, at normal incidence. An excellent antireflection property of a wide range of incidence angles was shown with the average reflection below 4% at 50°. Compared with the unpatterned ultraviolet-curable resin coating, the resulting sub-wavelength moth-eye structure also exhibited increased hydrophobicity in addition to antireflection. This R2P method is especially suitable for large-area product preparation and the biomimetic moth-eye structure with multiple performances can be applied to optical devices such as display screens, solar cells, or light emitting diodes.

BACKGROUND: In women, adhering to an overall healthy lifestyle is associated with a dramatically reduced risk of cardio-metabolic disorders. Whether such a healthy lifestyle exerts an intergenerational effects on child health deserves examination. METHODS: We included 5,701 children (9-14 years old at baseline) of the Growing Up Today Study 2, and their mothers, who are participants in the Nurses’ Health Study II. Pre-pregnancy healthy lifestyle was defined as a normal body mass index, no-smoking, physical activity ≥150min/week, and diet in the top 40% of the Alternative Healthy Eating Index–2010. Obesity during childhood and adolescence was defined using the International Obesity Task Force age- and sex-specific cutoffs. Multivariable log-binominal regression models with generalized estimating equations were used to evaluate the association of pre-pregnancy healthy lifestyle and offspring obesity. RESULTS: We identified 520 (9.1%) offspring who became obese during follow-up. A healthy body weight of mothers and no smoking before pregnancy were significantly associated with a lower risk of obesity among offspring: the relative risks [RRs; 95% confidence intervals (CIs)] were 0.37 (0.31-0.43) and 0.64 (0.49-0.84), respectively. Eating a healthy diet and regular moderate-to-vigorous physical activities were inversely related to offspring obesity risk, but these relations were not statistically significant. Compared to children of mothers who did not meet any low-risk lifestyle factors, offspring of women who adhered to all four healthy lifestyle factors had 75% lower risk of obesity (RR 0.25, 95%CI 0.14-0.43). CONCLUSION: Adherence to an overall healthy lifestyle before pregnancy is strongly associated with a low risk of offspring obesity in childhood, adolescence, and early adulthood. These findings highlight the importance of an overall healthy lifestyle before pregnancy as a potential strategy to prevent obesity in future generations.