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An interpersonal network within a firm serves as a primary knowledge base for organizational innovation. In this article, we propose that intrafirm network connectivity, which is measured by the transitivity of an intrafirm network, has a nonlinear effect on firm innovation performance. Furthermore, on the basis of the literature on environmental contingency, we propose that two dimensions of environmental uncertainty (i.e., environmental munificence and dynamism) moderate the influence of intrafirm network connectivity on firm innovation performance. To examine our hypotheses, we collect the profiles of firms in the pharmaceutical and biotechnology industries from the COMPUSTAT database and patent data from the United States Patent and Trademark Office database for the period of 1991–2012. Our longitudinal study finds an inverted U-shaped relationship between intrafirm network connectivity and firm innovation performance, and such a relationship is moderated by environmental munificence but not by environmental dynamism.

Action recognition is an important yet challenging problem. While attention mechanism is widely used to extract informative features for action recognition, most previous attention models regard spatial attention and temporal attention to be independent. In this paper, we propose a novel nesting spatiotemporal attention network (NST) model in which the spatial attention and the temporal attention closely nests and interact with each other. A nesting spatiotemporal attention block contains a spatial attention module and a nested temporal attention module. The spatial attention module learns features to assign different weights for the spatial areas in each video frame. Based on the spatial attention areas, the temporal attention module assigns different weights for different frames. In this way, the most informative regions in each frame and the most key frames in the video sequence are jointly mined and enhanced. An overall architecture is constructed by inserting the nesting spatiotemporal attention blocks into base networks for action recognition. The proposed model was tested on challenging datasets and the experimental results show that our method outperforms other comparison methods.

Low-carbon transformation has become a key priority in China, as demonstrated in the implementation of the Carbon Peak, Carbon Neutralization policy, leading to increasing concern of environmental performance at the corporate level. This paper measures the carbon emission of 1,089 Chinese companies through the EIO-LCA-based approach. Then we examine the impacts of international crude oil price fluctuations and the corporate development level on carbon emissions of individual companies. Our results indicate that an increase in international crude oil price uncertainty could inhibit the company’s carbon emission. In parallel, we find that there might exist an environmental Kuznets curve (EKC) inverted U-shaped correlation between the company’s development level and its environmental performance. However, some exceptions to corporate carbon performance may emerge, resulting from specific corporate characteristics such as the state-owned nature and whether the firm is listed on the stock exchange. Our results could help companies optimize their internal carbon emission structure during the low-carbon transition process and contribute to effective policy regulations towards the target of carbon reduction.

Purpose To investigate the success rate of the Tübingen hip flexion splint (THFS) for the treatment of developmental dysplasia of the hip (DDH), of different severity as per the Graf classification, among infants younger than six months of age. The type and incidence rate of complications associated with THFS treatment were also evaluated. Methods The following databases were searched using keywords and limited for age less than six months: PubMed, Embase, Web of Science, Cochrane Library, and SinoMed, between inception and July 2020. Articles were screened and extracted by two researchers, and the quality of the included literature was evaluated (methodological index for non-randomized studies criteria). R studio 1.3 was used for statistical analysis. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results After screening, eight articles were included in the analysis, contributing 1211 hips (875 patients). The overall success rate of THFS treatment is 91% (95% confidence interval (CI) 0.82 to 0.95). The success rate by Graf type is as follows: type-II, 98% (95% CI 0.94 to 1.00); type-III, 96% (95% CI 0.88 to 1.00); and type-IV, 32% (95% CI 0.18 to 0.47). Complications (24/1211, 2%) included transient femoral nerve palsy (n = 1); avascular necrosis of the femoral head (n = 9) and residual acetabular dysplasia (n = 14). Conclusion THFS treatment is successful for Graf type-II and –III, but low for type-IV, with a low rate of complication. THFS may be an effective treatment option for DDH among infants less than six months of age. However, those with Graf type-IV require close monitoring. Level of Evidence III

Background There has been a considerable focus on the changes of functional connections between brain regions in patients with type 2 diabetes mellitus (T2DM) by previous resting-state functional magnetic resonance imaging (rs-fMRI) studies. However, little is known about the function of brain information integration between the two hemispheres of the brain. This study explores differences in interhemispheric coordination between T2DM patients and normal control (NC) subjects using the voxel-mirrored homotopic connectivity (VMHC) method. We also assess whether differences in VMHC were relevant to cognitive dysfunction in T2DM patients. Methods Sixty-nine T2DM patients and 69 NC subjects were enrolled (matched for age, sex and education level). All participants underwent cognitive assessments. VMHC between brain regions was obtained by rs-fMRI analysis. Partial correlation analysis (after controlling for age, sex and education level) was used to explore the correlation between VMHC value and neuropsychological tests. Results Compared with NC subjects, T2DM patients exhibited significantly lower VMHC in the medial orbitofrontal gyrus cortex (mOFC), anterior cingulate gyrus, inferior parietal lobe, superior and middle temporal gyrus (MTG), middle occipital gyrus, and superior occipital gyrus. Moreover, after applying Bonferroni correction, the Montreal Cognitive Assessment (MoCA) score and VMHC value for the MTG were significantly positively correlated in T2DM patients. In contrast, T2DM patients exhibited higher VMHC in the cerebellum posterior lobe and tonsil and inferior temporal gyrus than the NCs. Conclusions Our study indicates that functional coordination between homotopic brain regions is generally impaired in T2DM patients. In brain regions with decreased VMHC in the default mode network (DMN), MTG impairment could serve as a critical node for T2DM-related cognitive dysfunction. Furthermore, the increased VMHC observed in the cerebellum and inferior temporal gyrus might indicate a functional coordination mechanism.

PurposeTo assess the effects of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography (OCTA).MethodsIn this prospective cross-sectional study, one eye each of 36 normal controls and 64 patients with glaucoma underwent 4.5 mm disc-centred and 6 mm macula-centred OCTA scans. The peripapillary nerve fibre layer plexus capillary density (NFLP-CD) and macular superficial vascular complex vessel density (SVC-VD) were measured using both a commercial algorithm (AngioAnalytics) and a custom algorithm (Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART)). The nerve fibre layer and ganglion cell complex thicknesses were measured on structural OCT.ResultsThe overall peripapillary NFLP-CD and macular SVC-VD measured with the two algorithms were highly correlated but poorly agreed. Among the normal controls, the perfusion measurements made by both algorithms were significantly correlated with age. AngioAnalytics measurements were also correlated with signal strength index, while COOL-ART measurements were not. These covariates were adjusted. The diagnostic accuracy, measured as the area under the receiver operating characteristic curve for glaucoma detection, was not significantly different between algorithms, between structural and perfusion parameters and between the peripapillary and macular regions (All p>0.05). The macular SVC-VD in the 6 mm square had a significantly higher diagnostic accuracy than that of the central 3 mm square area (p=0.005).ConclusionsAngioAnalytics and COOL-ART vessel density measurements are not interchangeable but potentially interconvertible. Age and signal strength are significant covariates that need to be considered. Both algorithms and both peripapillary and macular perfusion parameters have similarly good diagnostic accuracy comparable to structural OCT. A larger macular analytic area provides higher diagnostic accuracy.

Depth completion is to predict a dense depth image from a raw sparse depth image with missing values, which is an important yet challenging problem in a myriad of vision, robotics, and multimedia applications. While previous studies have made substantial progress in this issue, most of them directly fuse RGB and depth features without considering the multiple latent cues in data. In this paper, we propose a multi-cue guidance network model for depth completion, which introduces multi-cue features to guide the regression of residual values. This network includes two major parts: multi-cue guidance structure and residual regression structure. The multi-cue guidance structure composed of two parallel convolutional sampling streams extracts features from the raw depth image and the corresponding RGB image, respectively. The extracted features are used as multi-cue guidance to combine with the depth image to feed the residual regression structure, where the estimated residual values are combined with the raw depth values to output the final dense depth values. By virtue of the multi-cue guidance and residual regression, the proposed model can leverage the multiple latent cues in the data to predict more accurate depth values. The proposed method was tested on two challenging datasets of outdoor and indoor scenes: KITTI benchmark and NYUv2 dataset. The experimental results show that the proposed method outperforms the comparison methods. Extensive ablation studies demonstrate the effectiveness of different modules in the proposed method.

BACKGROUND: Recent breakthroughs in therapies with immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, only 15–25% of patients respond to the ICIs therapy, and methods to identify those responsive patients are currently a hot research topic. PD-L1 expression measured on tumor tissues using immunohistochemistry (IHC) was approved as one of the companion diagnostic methods, but it is invasive and cannot be used to monitor dynamic changes in PD-L1 expression during treatments. METHODS: In this study, we developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform. This assay detected PD-L1 expression levels on tumor-derived exosomes from the lung cancer cell lines A549 and SK-MES1. In addition, 35 plasma samples from patients with lung cancer were tested with this assay and the results were compared to the tissue PD-L1 expression levels represented by the tumor proportion score (TPS). RESULTS: PD-L1 TPS-positive patients (≥1% IHC TPS) had significantly higher Simoa Epcam-PD-L1 signals than TPS-negative patients (

Synergistically regulating carrier and phonon transport on the nanoscale is extremely difficult for all thermoelectric (TE) materials without cage structures. Herein BaFe12O19/Bi2Te25Se0.5 thermoelectromagnetic nanocomposites are designed and synthesized as a benchmarking example to simultaneously tailor the transport properties on the nanoscale. A magneto-trapped carrier effect induced by BaFe12O19 hard-magnetic nanoparticles (NPs) is discovered, which can lower the carrier concentration of n-type Bi2Te2.5Se0.5 matrix by 16%, and increase the Seebeck coefficient by 16%. Meanwhile, BaFe12O19 NPs provide phonon scattering centers and reduce the thermal conductivity by 12%. As a result, the ZT value of the nanocomposites is enhanced by more than 25% in the range of 300–450 K, and the cooling temperature difference increases by 65% near room temperature. This work greatly broadens the commercial application potential of n-type Bi2Te2.5Se0.5, and demonstrates magneto-trapped carrier effect as a universal strategy to enhance the electro-thermal conversion performance of TE materials with high carrier concentration.

Objective Studies have suggested that coronavirus disease 2019 (COVID-19) appears to be more serious in patients with gastrointestinal symptoms. This meta-analysis was conducted to explore the relationship between gastrointestinal symptoms and the severity of COVID-19. Methods We searched PubMed, Web of Science, Science Direct, Embase, and Google Scholar on 16 October 2020, to identify observational studies that provided data on gastrointestinal symptoms and severity of COVID-19. Gastrointestinal symptoms include diarrhea, abdominal pain, nausea, and vomiting. The severe rate and the odds ratio (OR) were pooled. Heterogeneity was assessed using the I2 statistic. Results A total of 21 studies with 5285 patients were included in this meta-analysis. The severe rate of COVID-19 patients with diarrhea was 41.1% [95% confidence interval (CI): 31.0-51.5%], and the OR of association between diarrhea and severe COVID-19 was 1.41 (95% CI: 1.05-1.89); sensitivity analysis showed that the results for the OR and 95% CI were unstable. For abdominal pain, the severe rate and OR of association with severe COVID-19 were 59.3% (95% CI: 41.3-76.4%) and 2.76 (95% CI: 1.59-4.81), respectively; for nausea, 41.4% (95% CI: 23.2-60.7%) and 0.92 (95% CI: 0.59-1.43), respectively; for vomiting, 51.3% (95% CI: 36.8-65.8%) and 1.68 (95% CI: 0.97-2.92), respectively. Conclusion The severe rate was more than 40% in COVID-19 patients with gastrointestinal symptoms. Abdominal pain was associated with a near 2.8-fold increased risk of severe COVID-19; the relationship between diarrhea and the severity of COVID-19 was regionally different; nausea and vomiting were limited in association with an increased risk of severe COVID-19.

Herein, we report the preparation and thermoelectric (TE) properties of flexible PEDOT:PSS/Cu2Se-based nanocomposite films on a nylon membrane using facile vacuum filtration and then hot pressing. The main composition of the composite film changed during hot pressing, causing the change of the carrier transport and TE performance intensively. Consequently, the optimized film shows a high power factor of 820 μW/mK2 at 400 K, which is 3 times as high as that of the nonhot-pressed one. The film shows excellent flexibility with 85% retention of the power factor after 1000 bending cycles around a 5 mm diameter rod. The outstanding flexibility results from a good combination between the nylon membrane and the Cu2Se-based nanoporous structured film. By pairing with n-type PEDOT/Ag2Se/CuAgSe films, a ten-legged flexible TE generator outputs maximum voltage and power of 50 mV and 1.55 μW, respectively, at a temperature difference of 44 K. Our research opens up a promising avenue to design high property flexible TE films for energy conversion.

A 135-Mb 0.021- $\mu \text{m}^{2}$ 6-T high-density SRAM bit cell with write-assist circuitries was successfully implemented by using 5-nm HK-metal gate FinFET with EUV and high-mobility channel (HMC) technology. This article proposes the metal capacitor coupling negative bitline (NBL) and the charge-sharing lower cell-VDD (CS-LCV) write-assist techniques to reduce the SRAM minimal supply voltage. Flying bitline (FBL) architecture is also implemented to improve the high-density SRAM macro-bit density by 5%. Silicon data show that both NBL and LCV write-assist techniques can improve the overall SRAM minimal supply voltage performance by more than 300 mV at the 95th percentile.

The diagnosis and therapy of tumors are challenging problems in the medical field. Peptides are derived from living organisms with excellent biocompatibility, low-toxicity/non-toxicity, and negligible immunogenicity, and they have been widely used in the field of biomedicine, especially in tumor sensing and treatment. In recent years, a series of technologies in peptide research (including polypeptide synthesis, phage screening, sequencing, and computer-aided molecular simulations) and the discovery of tumor targeting peptide have been developed. In this review, we summarized the progress of peptide-based materials in tumor therapy, including the development and screening of peptides, and two peptide targeting tumor strategies: targeting tumor high-expressing receptors and targeting tumor microenvironment. We also summarized various tumor imaging methods and treatment methods based on peptides. Furthermore, the advantages and challenges of peptides in the current tumor field and the possible solutions are also discussed.

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood–brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Task-free attention has gained intensive interest in the computer vision community while relatively few works focus on task-driven attention (TDAttention). Thus this paper handles the problem of TDAttention prediction in daily scenarios where a human is doing a task. Motivated by the cognition mechanism that human attention allocation is jointly controlled by the top-down guidance and bottom-up stimulus, this paper proposes a cognitively-explanatory deep neural network model to predict TDAttention. Given an image sequence, bottom-up features, such as human pose and motion, are firstly extracted. At the same time, the coarse-grained task information and fine-grained task information are embedded as a top-down feature. The bottom-up features are then fused with the top-down feature to guide the model to predict TDAttention. Two public datasets are re-annotated to make them qualified for TDAttention prediction, and our model is widely compared with other models on the two datasets. In addition, some ablation studies are conducted to evaluate the individual modules in our model. Experiment results demonstrate the effectiveness of our model.

Chronic obstructive pulmonary disease (COPD) is becoming a leading cause of morbidity and mortality in China. In the IMPACT trial, fluticasone furoate[FF]/umeclidinium[UMEC]/vilanterol[VI] single-inhaler triple therapy demonstrated lower rates of moderate/severe exacerbations than dual therapy with FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations. This analysis investigates the China cohort and its consistency with the overall ITT population. 10,355 patients were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg for 52 weeks. Endpoints included: annual rates of exacerbations, time-to-first on-treatment moderate/severe exacerbation and change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week-52. Clinical trial registration is NCT02164513 (CTT116855). 535 patients (5.2%) were from China. Annual on-treatment moderate/severe exacerbation rate was 0.81 with FF/UMEC/VI versus 0.96 with FF/VI (rate ratio: 0.84; 95% confidence interval [CI]: 0.64, 1.11; p = .227) and 0.80 with UMEC/VI (rate ratio: 1.02; 95% CI: 0.72, 1.44; p = .929). Hazard ratio for time-to-first moderate/severe exacerbation was 0.84 (95% CI: 0.63, 1.11; p = .218) for FF/UMEC/VI versus FF/VI and 0.89 (95% CI: 0.62, 1.27; p = .516) versus UMEC/VI. Significant improvements in mean change from baseline in trough FEV1 were observed for FF/UMEC/VI versus FF/VI (treatment difference 137 mL; 95% CI: 86, 188; p p = .050). Health status was improved with FF/UMEC/VI versus both dual therapies. Results were similar to the overall ITT population. No new safety signals were identified. Single-inhaler triple therapy with FF/UMEC/VI versus FF/VI or UMEC/VI reduced the rate and risk of exacerbations, and improved lung function and health status in the China cohort similar to the overall ITT population. No new safety signals were identified.

Background Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. Methods In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2–12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. Results Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2–6 years). Drug-related adverse events occurred in Conclusions This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2–12 years), supporting its use in clinical treatment for AR children, including younger children aged 2–6 years. Impact The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2–6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2–6 years.

Objective: The objective of this study is to explore the imaging features of abdominal Computed Tomography (CT) in patients with surgical acute abdominal perforation and to improve the diagnostic ability of perforated acute appendicitis (PAA). Method: Patients with suspected acute appendicitis and abdominal pain are selected as the study objects. According to the surgical records and pathological results, the patients are divided into PAA group and nonperforated acute appendicitis (NPAA) group. All patients are examined by abdominal CT. Postprocessing reconstruction technology such as multiple planar reconstruction (MPR) algorithm and curved planar reformat (CPR) algorithm are used as assistance to display the appendix, analyze and compare the images, observe the image performance of abdominal CT, and measure the diameter of the appendix. Results: The incidence of PAA specific signs (i.e. cellulitis around the appendix, abscess around the appendix, enhancement defect of the appendix wall, air accumulation outside the appendix cavity, fecal stone outside the appendix cavity) in PAA group is significantly higher than that in NPAA group (P < 0.05). Appearance of at least one specific sign for the diagnosis of PAA is 95.65%, the specificity is 92.59%, and the accuracy is 94.00%. The diameter of appendix in PAA group is significantly larger than that in NPAA group (P < 0.05). Compared with the diagnosis of simple specific signs, the specificity and accuracy of the combination of appendiceal diameter and specific signs in the diagnosis of PAA have been improved. Conclusion: With the help of MPR algorithm and CPR algorithm, abdominal CT imaging technology can accurately identify PAA and NPAA, which has important diagnostic value.

Nanomagnetic devices, such as nano-field effect transistor biosensors and radio frequency magnetic induction therapies, came into being with the development of medical nanomaterials. The application of nanomagnetic materials in the treatment of cancers is rapidly becoming increasingly important because of its ability to target therapy and diagnose early. In this review, an untechnical overview of the fundamental of magnetism in nanomaterials and an illustration of how these materials are applied are presented. The applications of nano-field effect transistor biosensors for the detection of tumor biomarker nanomaterials in the therapy and diagnosis of cancers and nanomagnetic materials are summarized in this paper. A systemic summary of the use of nanomagnetic materials and nano-filed effect transistor biosensors for the treatment and diagnosis of tumors is also provided in the review.

Due to the limited thermoelectric (TE) performance of conducting polymers and rigidity of inorganic materials, it is still a huge challenge to prepare low-cost, highly flexible, and high-performance TE materials. Herein, we fabricated n-type Ag2Se films using a porous nylon membrane as a flexible substrate by vacuum-assisted filtration, followed by hot pressing. A very high power factor of ∼1882 μW m-1 K-2 at room temperature is obtained. The high power factor is mainly the result of the high density of the Ag2Se film and the tuned grain orientation, which is realized by the synthesis of multisized Ag2Se nanostructures. The film also exhibits excellent flexibility with 90.7% retention of the power factor after bending around a rod of 4 mm radius for 1000 times. A four-leg TE generator is assembled with the Ag2Se film, and its maximum output power is up to 3.2 μW at a temperature difference of 30 K, corresponding to the maximum power density of 22.0 W m-2 and a normalized maximum power density of 408 μW m-1 K-2. This work provides an effective route to achieve high-power-factor, high-flexibility, and low-cost TE films.

This study uses the dies of the dray fasteners processing graphics provided by the fastener’s industry to establish 3D dies and components solid models based on the embedded drawing function tools provided by the component model (Standard.ipt) of Autodesk Inventor CAD software. After finishing the dies and components drawing, the integrated assembly drawing of dies can be obtained through the assembly model (Standard.iam) firstly. Three stages forming processes can be conducted and carried out the FEM simulation to check the forming acceptance. The effective stress, the effective strain, the velocity field, and the forging force can be obtained by the FEM simulation. Moreover, the realistic experiment can be performed to verify the acceptance of FEM simulation. The dimensions of final product can be measured to get the errors between FEM and experiment. It is noted that the errors show a good agreement with the experiment.

Multiple microRNAs (miRs) have also been implicated in ischemic brain injury. This research intended to probe the regulatory function and the mechanism of miR‐15a on the ischemic brain injury induced by oxygen‐glucose deprivation/reoxygenation (OGD/R) in neurons of rats. The OGD/R model was established with the cortical neurons separated from rats. After transfection with miR‐15a mimic negative control (NC), miR‐15a mimic, miR‐15a inhibitor NC and miR‐15a inhibitor, the OGD/R‐induced apoptosis were detected. Using bioinformatic softwares including TargetScan, miRanda, and miRWalk to predict the underlying targets of miR‐15a, and the binding of miR‐15a with brain‐derived neurotrophic factor (BDNF) were validated with double‐fluorescein reporter assay system. The expression levels of BDNF mRNA and protein were detected with qRT‐PCR and western blot. The effect of miR‐15a on PI3K/AKT pathway in neurons submitted to OGD/R was also investigated. The findings showed that miR‐15a may mediate the apoptosis of neurons submitted to OGD/R, and lower expression of Bcl‐2 and higher expression of Bax and cleaved caspase‐3 were observed. BDNF was screened as the candidate target, and the direct binding of miR‐15a with 3′‐UTR of BDNF were verified. Further research showed that miR‐15a downregulated the expression of BDNF mRNA and protein, thus exerted negative regulatory effect on the OGD/R injury. PI3K/AKT pathway may be related to the regulatory effect of miR‐15a. Our findings contribute to uncovering novel pathogenesis for ischemic brain injury.

Introduction The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. Objectives To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA‐CB) by different radiological classifications of mucus plugs. Methods ABPA‐CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA‐CB patients were divided into two groups based on the presence of high‐attenuation mucus (HAM) or low‐attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. Results A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish‐black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. Conclusions The clinical characteristics and prognosis of ABPA‐CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

In this paper, we construct the input–output relationships of a three-mode nonlinear beam splitter (TNBS) mathematically, and a set of special solutions for the input–output equations are given. By combining two TNBSs and a phase shifter, we propose a scheme for a three-mode nonlinear interferometer (TNI) and give the input–output expression of the whole TNI. Then, we study the phase sensitivity of the TNI by giving input states and detection scheme. In addition, we also calculate the phase sensitivity of a Mach–Zehnder interferometer (MZI), SU(1,1) interferometer (SU(1,1)I) and modified Mach–Zehnder interferometer (MMZI), and we discuss the relationships of phase sensitivity between the MZI, SU(1,1)I, MMZI and TNI. Finally, in the presence of photon losses, we discuss the phase sensitivity of the four different interferometers and make detailed comparisons. It is shown that the TNI has the best robustness against photon losses under certain conditions with the same parameters.

Background: Globally, hepatocellular carcinoma (HCC) is the sixth most frequent malignancy with a high incidence and a poor prognosis. Immune cell infiltration (ICI) underlies both the carcinogenesis and immunogenicity of tumors. However, a comprehensive classification system based on the immune features for HCC remains unknown.Methods: The HCC dataset from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts was used in this study. The ICI patterns of 571 patients were characterized using two algorithms: the patterns were determined based on the ICI using the ConsensusClusterPlus package, and principal component analysis (PCA) established the ICI scores. Differences in the immune landscape, biological function, and somatic mutations across ICI scores were evaluated and compared, followed by a predictive efficacy evaluation of ICI scores for immunotherapy by the two algorithms and validation using an external immunotherapy cohort.Results: Based on the ICI profile of the HCC patients, three ICI patterns were identified, including three subtypes having different immunological features. Individual ICI scores were determined; the high ICI score subtype was characterized by enhanced activation of immune-related signaling pathways and a significantly high tumor mutation burden (TMB); concomitantly, diminished immunocompetence and enrichment of pathways associated with cell cycle and RNA degradation were found in the low ICI score subtype. Taken together, our results contribute to a better understanding of an active tumor and plausible reasons for its poor prognosis.Conclusion: The present study reveals that ICI scores may serve as valid prognostic biomarkers for immunotherapy in HCC.

Background Brain metastasis (BM) is thought to be related to the mortality and poor prognosis of non-small cell lung cancer (NSCLC). Despite promising development of NSCLC treatment, the treatment of NSCLC BM is still not optimistic due to the existence of the blood-brain barrier (BBB) that prevent drug penetration, as well as the short median survival time of the patients left for treatment. In this context, further development of quick and effective pre-clinical models is needed in NSCLC BM treatment. Here, we report a model system using zebrafish to promote the development of drugs for patients with NSCLC BM. Methods Three different NSCLC cell lines (H1975, A549 and H1299) were used to establish zebrafish BM models. The embryo age and cell number for injection were first optimized. Metastatic cells were observed in the brain blood vessels of zebrafish and were verified by hematoxylin-eosin (HE) staining. Then, the metastasis potentials of H1975 and A549 with manipulated microRNA-330-3p (miR-330-3p) expression were also investigated. Finally, sensitivities of H1975 and A549 to osimertinib and gefitinib were tested. Results This zebrafish BM model could distinguish NSCLC cell lines with different BM potential. Over-expressed miR-330-p significantly improved the BM potential of the A549 cells while knockdown miR-330-p reduced the BM ability of the H1975 cells. Both osimertinib and gefitinib showed inhibition effect in zebrafish BM model with the inhibition rate higher than 50 %. H1975 cell showed much higher sensitivity to osimertinib rather than gefitinib both in vivo and in vitro. Conclusions We established zebrafish brain metastasis model for studying mechanism and treatment of NSCLC BM. This study provided a useful model for NSCLC brain metastasis that could be used to study the mechanism that drive NSCLC cells to the brain as well as identify potential therapeutic options.

This paper presents an 8-channel array of low-noise (30.3 fA/Hz) current sensing front-ends with on-chip microelectrode electrochemical sensors. The analog front-end (AFE) consists of a 1st-order continuous-time delta-sigma (CT) modulator that achieves 123 fA sensitivity over a 10 Hz bandwidth and 139 dB cross-scale dynamic range with a 2-bit programmable current reference. A digital predictor and tri-level pulse width modulated (PWM) current-steering DAC realize the equivalent performance of a multi-bit in an area- and power-efficient manner. The AFE consumes 50.3 W and 0.11 mm2 per readout channel. The proposed platform was used to observe protein-ligand interactions in real-time using transient induced molecular electronic spectroscopy (TIMES), a label- and immobilization-free biosensing technique.

Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear.Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function.Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) >300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR > 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR > 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR > 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48).Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.

Louis Tong,1– 4 Lei Zhou,3– 5 Siew Kwan Koh,5 Yan Gao,5 Hla Myint Htoon,1,3 AiHua Hou,1,3 Lu Deng,6 Qi-Ping Wei,7 Pat Lim8 1Ocular Surface Research Group, Singapore Eye Research Institute, Singapore; 2Corneal and External Eye Disease Service, Singapore National Eye Centre, Singapore; 3Eye-Academic Clinical Program, Duke-National University of Singapore (NUS) Medical School, Singapore; 4Department of Ophthalmology, Yong Loo Lin School of Medicine, NUS, Singapore; 5Ocular Proteomics Platform, Singapore Eye Research Institute, Singapore; 6Department of Statistics and Applied Probability, Faculty of Science, NUS, Singapore; 7Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 8Singapore Chung Hwa Medical Institution, SingaporeCorrespondence: Louis TongSingapore National Eye Centre, 11, Third Hospital Avenue, 168751, SingaporeTel +65 9818 6221Fax +65 62252568Email Louis.tong.h.t@singhealth.com.sgLei ZhouSingapore Eye Research Institute, The Academia, 20 College Road, Level 6, 169856, SingaporeEmail zhou.lei@seri.com.sg

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p

As an innovative green financial tool, green corporate asset-backed securities can effectively solve the problems of narrow financing channels and maturity mismatches for green projects, which can help achieve green and low-carbon development, carbon peaking, and carbon neutrality goals. In this paper, we examine the financing cost advantages of green corporate asset-backed securities and the related impact factors through a combination of empirical and case studies. Empirical research based on the propensity score matching method (PSM) shows that China’s green corporate asset-backed securities issuance rates are 36.97°bps lower than traditional corporate asset-backed securities on average. Credit rating, issuance scale, issuance interest rate, issuance period, and green factors have become the main impact factors of green corporate asset-backed securities financing advantages.

Salmonella is one of the major pathogenic bacteria causing food-borne diseases. The rapid detection of Salmonella in food is of great significance to food safety. In this study, the loop-mediated isothermal amplification (LAMP) method was developed and the primers were designed targeting the invA gene of Salmonella. Then, the standard samples of recombinant invA-plasmid and 100 retail meat samples were tested by LAMP and compared with the results tested by the conventional PCR and the routine China National Food Safety Standard Methods for Food Microbiological Examination-Salmonella (GB/T4789.4-2016), respectively. The results showed that Salmonella strains of 8 different serotypes were amplified successfully by the developed LAMP assay. And, it was 1000-fold more sensitive than the conventional PCR with the analytical sensitivity of 8×102 copies/μL of the standard sample of invA-plasmid. The results were visualized directly by adding Calcein/MnCl2 into the LAMP reaction tube and the positively amplified products turned green after an incubation of 2 min. In the parallel detection, the positive rate of Salmonella by the LAMP assay was highly correlated with the routine China national standard method. The results of the study demonstrated that the developed LAMP assay is a simple, rapid, strongly specific, highly sensitive and visual detection method for Salmonella.

The aim of this study was to apply machine learning methods to deeply explore the risk factors associated with adverse drug events (ADEs) and predict the occurrence of ADEs in Chinese pediatric inpatients. Data of 1,746 patients aged between 28 days and 18 years (mean age = 3.84 years) were included in the study from January 1, 2013, to December 31, 2015, in the Children’s Hospital of Chongqing Medical University. There were 247 cases of ADE occurrence, of which the most common drugs inducing ADEs were antibacterials. Seven algorithms, including eXtreme Gradient Boosting (XGBoost), CatBoost, AdaBoost, LightGBM, Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and TPOT, were used to select the important risk factors, and GBDT was chosen to establish the prediction model with the best predicting abilities (precision = 44%, recall = 25%, F1 = 31.88%). The GBDT model has better performance than Global Trigger Tools (GTTs) for ADE prediction (precision 44 vs. 13.3%). In addition, multiple risk factors were identified via GBDT, such as the number of trigger true (TT) (+), number of doses, BMI, number of drugs, number of admission, height, length of hospital stay, weight, age, and number of diagnoses. The influencing directions of the risk factors on ADEs were displayed through Shapley Additive exPlanations (SHAP). This study provides a novel method to accurately predict adverse drug events in Chinese pediatric inpatients with the associated risk factors, which may be applicable in clinical practice in the future.

Objectives No large sample studies have been designed to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) in the primary and secondary prevention of respiratory disorders. We aimed at evaluating the relationship between use of GLP1RAs and occurrence of 12 kinds of respiratory disorders. Methods Large randomized placebo-controlled trials of GLP1RAs were included. We conducted meta-analysis using random-effects model and measured heterogeneity using I2 . Treatment effect was presented as risk ratio (RR) and 95% confidence interval (CI). Results Seven trials including 55922 participants were included in meta-analysis. The occurrence rates of various respiratory disorders were low, with the minimum of 0.02% (pulmonary fibrosis) and the maximum of 2.31% (pneumonia). Although not reaching statistical significance, GLP1RAs versus placebo showed the reduced trends in the risks of 9 kinds of respiratory disorders including pneumonia (RR 0.89, 95% CI 0.78-1.01), squamous cell carcinoma of lung (SCCL; RR 0.55, 95% CI 0.25-1.21), asthma (RR 0.82, 95% CI 0.51-1.32), and chronic obstructive pulmonary disease (COPD; RR 0.89, 95% CI 0.73-1.10), but the increased trend in interstitial lung disease (ILD; RR 1.89, 95% CI 0.87-4.08). GLP1RAs had neutral effects on two other respiratory disorders. Heterogeneity in any meta-analysis was absent or low. Conclusion GLP1RAs show the reduced trends in the risks of 9 kinds of respiratory disorders (e.g., pneumonia, SCCL, asthma, and COPD), but the increased trend in the risk of ILD. However, these findings need to be validated by further studies due to the low incidence rates of all the respiratory disorders.

Here, we fabricated a novel photoelectrochemical (PEC) aptasensor based on Br,N-codoped TiO2/CdS quantum dots (QDs) sensitization structure with excellent energy level arrangement for supersensitiv...

Declarative memory and procedural memory have their own independent information processing channels, but also share common processing mechanisms. Converging evidence recently shows that declarative learning can inhibit the performance of procedural memory. However, other studies also show that there may be semantic association effect and sequence expectation effect. We assumed that this interference effect of declarative memory on procedural memory could vanish or even be transformed into the enhancing effect when there was semantic association or both semantic association and sequence matching existed between two tasks. Experiment 1 examined the role of semantic association in the influence of declarative memory on procedural memory. We found that the performance of the semantic association group was significantly better than that of the baseline group, while the performance of the semantic independent group was significantly worse than that of the baseline group. In Experiment 2, based on semantic association, the role of sequence matching in the impact of declarative memory on procedural memory was tested. As a result, the accuracy of the sequence matching group was significantly higher than that of the baseline group, while the accuracy of the sequence mismatched group was not significantly different from that of the baseline group. The results of the two experiments suggest that the effect of declarative memory on procedural memory is not a fixed relationship. It is modulated by semantic association and sequence matching between two tasks. Declarative memory can interfere with procedural memory when two tasks have no semantic association, however, when there is semantic association the interference effect can vanish. Further, when both semantic association and sequence matching exist, the interference effect can be reversed into an enhancing effect.

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The unknown statistical distributions of two effective elastic properties of Sn-3.0Ag-0.5Cu solder joint of leadless chip resistors (LCRs), induced by an assembly condition, are determined by the advanced statistical model calibration. Two key elements are involved in the model calibration: an uncertainty propagation (UP) analysis and an optimization process using a calibration metric. In this paper, the UP analysis utilizes an advanced approximate integration method, which allows us to take into account the statistical variations of six additional known input variables, including die thickness, solder joint height, termination length, and thickness and elastic moduli of a printed circuit board. The cyclic bending test results of LCR assemblies are used in conjunction with the maximum-likelihood metric to obtain the statistical distributions of the effective properties. The cycles-to-failure distribution of the identical LCR assemblies subjected to a different loading level is predicted accurately by the calibrated model, which corroborates the validity of the proposed approach.

This paper deals with distributed registration of a sensor network for target tracking in the presence of false and/or missed measurements. Each sensor acquires measurements of the target position in local coordinates, having no knowledge about the relative positions (referred to as drift parameters) of its neighboring nodes. A distributed Bernoulli filter is run over the network to compute in each node a local posterior target density. Then a suitable cost function, expressing the discrepancy between the local posteriors in terms of averaged Kullback–Leibler divergence, is minimized with respect to the drift parameters for sensor registration purposes. In this way, a computationally feasible optimization approach for joint sensor registration and target tracking is devised. Finally, the effectiveness of the proposed approach is demonstrated through simulation experiments on both tree networks and networks with cycles, as well as with both linear and nonlinear sensors.

We propose a multi-mode nonlinear interferometers structure by cascading several multi-mode beam splitters (MBS) and nonlinear phase shifters (NPS), in which multiple phases can be estimated simultaneously. Specially, we mainly discuss two phases estimation in a three-mode nonlinear interferometer with single photons as inputs. The phase sensitivity of the three-mode nonlinear interferometer can be discussed by the quantum Fisher information matrix (QFIM) method after the states undergo the nonlinear phase shifters, and can also be studied by classical Fisher information matrix (CFIM) method in the interferometer’s output ports. It is shown that the precision given by CFIM can achieve the bound of QFIM. Finally, we make a comparison with an optimal probe state in terms of the total variance and discuss the relationship of the total variance among three different phase estimation schemes.

It is of prime importance to harness the transfer and flow of photogenerated electrons and holes to elongate the lifetimes of charge carriers and enhance the activity of semiconductor photocatalyst, which can be achieved by hybridizing the photocatalyst with appropriate cocatalysts with right electronic properties and placement. Herein, MXenes, a young family of two-dimensional transition metal carbides, are exploited as a hole mediator to enhance the photocatalytic activity of TiO 2 . We grow TiO 2 sheets exposing (001) surfaces on layered Ti 3 C 2 T x , and then photodeposited Cu 2 O nanodots on TiO 2 . We experimentally prove that the Ti 3 C 2 T x MXene from the wet HF etching method behaves as a low work function material ( ϕ = 3.4 eV). Thanks to this unique electronic property, the photogenerated electrons on TiO 2 hybridized with Ti 3 C 2 T x accumulate and tunnel to Cu 2 O to reduce it to elemental Cu as a reduction cocatalyst. The resulting Cu/TiO 2 @Ti 3 C 2 T x photocatalyst efficiently split water to produce hydrogen at 860 μmol g −1 h −1 . The results presented here demonstrate the promise of MXene materials in photocatalytic solar energy utilization. The insight into the electronic property of MXene sheds light on the new approach to the rational design of high-efficiency photocatalysts composed of MXenes.

During the past decades, the rapidly-evolving cancer is hard to be thoroughly eliminated even though the radiotherapy and chemotherapy do exhibit efficacy in some degree. However, a breakthrough appeared when the adoptive cancer therapy [1] was developed, especially T cells armed with chimeric antigen receptors (CARs) showed great potential in tumor clinical trials recently. CAR-T cells successfully elevated the efficiency and specificity of cytotoxicity. In this review, we will talk about the design of CAR and CAR-included combinatory therapeutic applications in the principles of systems and synthetic immunology. Keywords: T cell signaling, Chimeric antigen receptor (CAR), Cell therapy, Immunotherapy, Tumor immunology, Systems and synthetic immunology, Systems and synthetic biology

Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown.Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages.In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells.These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.

Background In this study, we have investigated the potential regulatory mechanisms of IL‐35 to relieve lupus nephritis (LN) through regulating Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway in mesangial cells. Results Among 105 significant differentially expressed proteins (DEPs) between juvenile systemic lupus erythematosus (JSLE) patients with LN and healthy controls, LAIR1, PDGFRβ, VTN, EPHB4, and EPHA4 were downregulated in JSLE‐LN. They consist of an interactive network with PTPN11 and FN1, which involved in IL‐35‐related JAK/STAT signaling pathway. Besides, urinary LAIR1 was significantly correlated with JSLE‐LN clinical parameters such as SLEDAI‐2K, %CD19+ B, and %CD3+ T cells. Through bioinformatics analysis of co‐immunoprecipitation with mass spectrometry results, including GO, KEGG, and STRING, five genes interacted with Lair1 were upregulated by IL‐35, but only Myh10 was downregulated. Therefore, we presumed an interactive network among these DEPs, JAK/STAT, and IL‐35. Moreover, the downregulated phosphorylated (p)‐STAT3, p‐p38 MAPK, and p‐ERK, and the upregulated p‐JAK2/p‐STAT1/4 in IL‐35 overexpressed mesangial cells, and RNA‐sequencing results validated the potential regulatory mechanisms of IL‐35 in alleviating JSLE‐LN disease. Moreover, the relieved histopathological features of nephritis including urine protein and leukocyte scores, a decreased %CD90+αSMA+ mesangial cells and pro‐inflammatory cytokines, the inactivated JAK/STAT signals and the significant upregulated Tregs in spleen, thymus and peripheral blood were validated in Tregs and IL‐35 overexpression plasmid‐treated lupus mice. Conclusions Our study provided a reference proteomic map of urinary biomarkers for JSLE‐LN and elucidated evidence that IL‐35 may regulate the interactive network of LAIR1‐PTPN11‐JAK‐STAT‐FN1 to affect JAK/STAT and MAPK signaling pathways to alleviate inflammation in JSLE‐LN. This finding may provide a further prospective mechanism for JSLE‐LN clinical treatment., A reference proteomic map of urinary biomarkers contributes to the diagnosis of JSLE‐LN. IL‐35 may interact with LAIR1‐PTPN11‐JAK‐STAT‐FN1 to affect JAK/STAT and MAPK signaling pathways to alleviate inflammation in vivo and in vitro. LAIR1 could be a novel potential target of IL‐35‐regulated JAK/STAT signaling pathway in JSLE‐LN.