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With the virus continuing to evolve, very virulent IBDV (vvIBDV) and novel variant IBDV (nvIBDV) have become the predominant epidemic strains in China, exacerbated by the widespread use of attenuated vaccine strains (attIBDV), making a complex infection situation of IBDV in the field. Therefore, developing a rapid and accurate high-resolution melting curve quantitative reverse transcription PCR (HRM-qRT-PCR) for the identification and pathotyping of IBDV is crucial for clinical monitoring and disease control. Extensive data analysis and genome-screening of the three dominant IBDV pathotypes identified a specific region (nucleotides 2450–2603 in segment A) with distinct GC content as the detection target. Experimental testing of HRM-qRT-PCR revealed distinct melting curves and high sensitivity, with the detection limits of 61.2 copies/μL, 61.1 copies/μL and 67.5 copies/μL for vvIBDV, nvIBDV and attIBDV, respectively. The method exhibited excellent specificity, with no inter-genotypes cross-reactivity among the three pathotypes and no reactivity to other common avian pathogens. Applied to samples with double and triple co-infections of different IBDV pathotypes, the method displayed specific melting peaks corresponding to the viruses present in the samples, with an accuracy rate of 100 %. This method precisely identifies and differentiates all the single or co-infected samples, generating distinct peaks corresponding to the Tm values of each virus pathotype in traditional melting curve plots. Furthermore, the method overcomes the limitations of traditional pathotyping methods, requiring only one reaction to achieve rapid viral pathotyping and facilitating quantitative analysis of viruses within the samples. This study introduces an innovative HRM-qRT-PCR method, offering new technology to rapid and accurate identification, pathotyping and quantification of vvIBDV, nvIBDV, and attIBDV. With strong discriminatory power, user-friendliness and a short processing time, this method is highly attractive for the rapid IBDV pathotyping in real-time large-scale epidemiological surveillance during outbreaks.

Novel variant infectious bursal disease virus (nvIBDV) is an emerging genotype (A2dB1b) that can cause severe and prolonged immunosuppression in young chickens. Despite current commercial vaccines being proven to lack complete protection against nvIBDV, it remains unclear whether the oil emulsion inactivated vaccines (OEVs) of the homologous and heterologous virus or booster immunization can provide effective protection. In this study, OEVs with two types of nvIBDV isolates QZ191002 (A-nv/B-nv) and YL160304 (A-nv/B-HLJ0504-like) were prepared and evaluated the protective effects of OEVs plus the booster immunizations with different current commercial vaccines against the challenge of nvIBDVs. The results from vaccination-challenge experiments showed that nvIBDV could break through the protection provided by only one immunization dose of the commercial vaccines, with the protection rates ranging from 40% to 60%. Interestingly, even with booster immunization with different commercial vaccines, the protection rates could only be increased to 60%–80%. As expected, only the OEVs of the homologous virus could provide 100% protection against the homologous nvIBDV, which could induce high-level specific antibodies, ameliorate target organ damage, and significantly reduce the viral load of the bursal in the challenged chickens. Notably, YL160304-OEV performed better than QZ191002-OEV, providing 100% protection not only against the challenge of homologous strain but also against that of heterologous QZ191002 strain. Antibody levels of the immunized chickens gradually increased after a short decline and reached the highest level on the age of 28 days. Similarly, the percentages of lymphocytes CD4+, CD8+ T, and B in peripheral blood lymphocytes (PBLs) were significantly increased on 21 d and 28 d. Notably, despite the nvIBDV, OEVs initially induced a delayed responses in the early stages but ultimately reach higher levels of CD4+ and CD8+ T lymphocytes. The results of study suggest that even booster immunization with different commercial vaccines cannot provide complete protection against nvIBDV, while the OEVs made by the nvIBDVs can provide full protection. Moreover, YL160304-OEV exhibits a broader protective spectrum against different nvIBDV strains, making it a potential candidate for the development of new vaccine.

ABSTRACT: Avian infectious bronchitis virus (IBV) still causes serious economic losses in the poultry industry. Currently, there are multiple prevalent genotypes and serotypes of IBVs. It is imperative to develop a new diagnosis method that is fast, sensitive, specific, simple, and broad-spectrum. A monoclonal hybridoma cell, N2D5, against the IBV N protein was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The N2D5 monoclonal antibody (mAb) and the previously prepared mouse polyclonal antibody against the IBV N protein were used to target IBV as a colloidal gold–mAb conjugate and a captured antibody, respectively, in order to develop an immunochromatographic strip. The optimal pH and minimum antibody concentration in the reaction system for colloidal gold–mAb N2D5 conjugation were pH 6.5 and 30 μg/mL, respectively. Common avian pathogens were tested to evaluate the specificity of the strip and no cross-reaction was observed. The sensitivity of the strip for detecting IBV was 10−1.4522 EID50/mL. The strip showed a broad-spectrum cross-reactive capacity for detecting IBV antigens, including multiple IBV genotypes in China and all of the seven serotypes of IBV that are currently prevalent in southern China. Additionally, the result can be observed within 2 min without any equipment. The throat and cloacal swab samples of chickens that were artificially infected with three IBV strains were tested using the developed strip and the qPCR method; the strip test demonstrated a high consistency in detecting IBV via qPCR gene detection. In conclusion, the immunochromatographic strip that was established is rapid, sensitive, specific, simple, practical, and broad-spectrum; additionally, it has the potential to serve as an on-site rapid detection method of IBV and can facilitate the surveillance and control of the disease, especially in resource-limited areas.

Photosynaptic transistors based on amorphous oxide semiconductors are a potential device to break von Neumann bottleneck due to their low consumption and integration of sensing, storage, and computing. Till now, there has been a lack of studies on the photosynaptic transistors based on zinc oxide (ZnO) under two dimensional optoelectronic controls. In this work, through size modulation, high-performance and back-end of line compatible 16-nm-thick ZnO thin film transistors (TFTs) by atomic layer deposition is fabricated with channel length and width of 10 and 30 μm, respectively. The device possesses outstanding electrical and photoelectric properties with a subthreshold swing of 273 mV/dec, a mobility of 28.0 cm2 (V s) 1, an on/off current ratio of 3.7 × 108, high responsivity of 2.9 × 105 A/W, and photo-to-dark-current ratio of 2.3 × 1010%. Moreover, three different trends of paired-pulse ratios under different Vg are exhibited with illustrations. This work demonstrates the potential of scaled down ZnO TFTs for the artificial neural networks.

Abstract Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Synthetic aperture LiDAR can generate point cloud data, which is widely used in 3-D scene reconstruction. However, existing point cloud object recognition methods are vulnerable to adversarial attacks, and such attacks are difficult to transfer to the physical world. Even if adversarial perturbations are added to physical objects, they are easily detectable by other sensors. Our proposed method includes two modules, R-D and D-R, which generate more concealed adversarial point cloud samples by modifying digital and physical features. The R-D module maps real-world entities to point cloud data in the digital world and generates adversarial samples by modifying signal amplitude values. The D-R module constructs adversarial objects by modifying the surface diffuse reflectance of the target object based on ray tracing and correspondences between digital and physical features. Our method is evaluated through experiments on attack effectiveness, robustness after subsampling and transferability, demonstrating its effectiveness, and achieving new state-of-the-art performance.

Abstract Background Although many studies have shown that high tibial osteotomy is appropriate for active patients, there are limited multifactorial studies on patients’ sport activity level after HTO in general population. Methods 158 patients who underwent HTO for knee osteoarthritis between January 2016 and December 2019 are included, with a 36-month follow-up. Information was collected from X-rays and questionnaire. The independent variables were age, sex, breadwinner (provide more than 50% income), sport activity level when the knee was pain-free before and after surgery, concomitant meniscal treatment history, Lysholm knee score, desire level for returning to sports. The 158 cases are divided into three groups according to their sports participation before and after operation, Chi-square tests and ANOVA analysis were adopted to identify the effect of these variables on sport activity level after HTO, and factors with statistical differences and clinical relevancies, or provided by previous research were assessed with the ordinal logistic regression analysis. Results According to sport activity level analysis, 28(17.7%) patients were categorized into the sport level-reduced group, 97(61.4%) patients into the sport level-unchanged group, and 33(20.9%) patients into the sport level-improved group. Upon ordinal logistic regression analysis, postoperative MA%, age, BMI, and preoperative Lysholm knee score were statistically significant. Conclusions Higher postoperative MA%, younger age, lower BMI, and lower Lysholm score are associate with improvement on activity level after HTO. This finding provides valuable references in operation option and rehabilitation planning.

Abstract Background Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. Methods The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)—induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/β-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. Results Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-β signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/β-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. Conclusions Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/β-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

Gold-based nanoparticles for surface-enhanced Raman scattering (SERS) imaging show great potential for precise tumor detection and photothermal therapy (PTT). However, the metabolizability of gold nanoparticles (Au NPs) raises big concerns. Herein, we designed a core-shelled nanostructure of copper sulfide (CuS)-coated Au NPs with surface pegylation (PEG-Au@CuS NSs). The excreted Au in the gallbladders at 1 h and 4 h in mice injected with PEG-Au@CuS NSs was 8.2- and 19.1-fold of that with the pegylated Au NPs (PEG-AuNPs) of the same Au particle size, respectively. By loading the Raman reporter 3,3′-Diethylthiatricarbocyanine iodide (DTTC) in the core–shell junction of PEG-Au@CuS NSs, the PEG-Au-DTTC@CuS NSs exhibited the Raman signal-to-noise (S/N) ratio of 4.01 after 24 h of intravenous (IV) injection in the mice bearing an orthotopic CT26-Luc colon tumor. By contrast, the DTTC-coated PEG-AuNPs (PEG-Au-DTTC NPs) achieved an S/N ratio of 2.71. Moreover, PEG-Au-DTTC@CuS NSs exhibited an increased photothermal conversion effect compared with PEG-Au-DTTC NPs excited with an 808-nm laser. PEG-Au-DTTC@CuS NSs enabled intraoperative SERS image-guided photothermal therapy for a complete cure of the colon tumor-bearing mice. Our data demonstrated that the PEG-Au-DTTC@CuS NSs are promising intraoperative Raman image-guided theranostic nanoplatform with enhanced hepatobiliary excretion.

Al-doped HfO2 (HAO) is regarded as one of the potential HfO2 ferroelectric materials owing to its compatibility with the front end of the line process in integration circuits. In this work, atomic layer deposited (ALD) HAO thin films with different Al-doping concentrations and the corresponding devices with Ti or W top electrodes have been explored. It is found that the HAO film properties and corresponding ferroelectric device performances depend greatly on the doping concentration. In the concentration range of 3.0%–5.0%, 4.5% is the most proper doping concentration to induce the ferroelectricity of the thin film. It is revealed by x-ray diffraction and photoelectron spectroscopy that the oxygen vacancies can be modulated by doping, thereby contributing to the formation of the ferroelectric orthorhombic phase. A high remnant polarization (2Pr) of 36.8 ± 0.7 μC/cm2 under 5 mV/cm sweeping is observed through electrical measurement in the device with a 4.5% HAO and W top electrode. In addition, it was found that the choice of W or Ti top electrodes would affect the leakage and breakdown characteristics of the device. This work reveals the mechanism of Al doping and electrode modulation of HfO2 device performance and promotes the development of HAO ferroelectric thin film devices.

ObjectiveThis retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy.MethodsClinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis.ResultsOverall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0–2), and 21 patients had a poor prognosis (mRS 3–6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p

Artificially modified adsorbing materials mainly aim to remedy the disadvantages of natural materials as much as possible. Using clay materials such as rectorite, sodium bentonite and metakaolinite (solid waste material) as base materials, hydrothermally modified and unmodified materials were compared. CM-HT and CM (adsorbing materials) were prepared and used to adsorb and purify wastewater containing malachite green (MG) dye, and the two materials were characterized through methods such as BET, FT-IR, SEM and XRD. Results: (1) The optimal conditions for hydrothermal modification of CM-HT were a temperature of 150 °C, a time of 2 h, and a liquid/solid ratio 1:20. (2) Hydrothermal modification greatly increased the adsorptive effect. The measured maximum adsorption capacity of CM-HT for MG reached 290.45 mg/g (56.92% higher than that of CM). The theoretical maximum capacity was 625.15 mg/g (186.15% higher than that of CM). (3) Because Al-OH and Si-O-Al groups were reserved in unmodified clay mineral adsorbing materials with good adsorbing activity, after hydrothermal modification, the crystal structure of the clay became loosened along the direction of the c axis, and the interlayer space increased to partially exchange interlayer metal cations connected to the bottom oxygen, giving CM-HT higher electronegativity and creating more crystal defects and chemically active adsorbing sites for high-performance adsorption. (4) Chemical adsorption was the primary way by which CM-HT adsorbed cationic dye, while physical adsorption caused by developed pore canal was secondary. The adsorption reaction occurred spontaneously.

Abstract Idiopathic pulmonary fibrosis (IPF) has been extensively studied in recent decades due to its rising incidence and high mortality. Despite an abundance of research, the mechanisms, immune-associated mechanisms, of IPF are poorly understood. While defining immunopathogenic mechanisms as the primary pathogenesis is controversial, recent studies have verified the contribution of the immune system to the fibrotic progression of IPF. Extensive evidence has shown the potential role of T cells in fibrotic progression. In this review, we emphasize the features of T cells in IPF and highlight the controversial roles of different subtypes of T cells or even two distinct effects of one type of T-cell in diverse settings, and multiple chemokines and cell products are discussed. Furthermore, we discuss the potential development of treatments targeting the immune molecules of T cells and the feasibility of immune therapies for IPF in clinical practice.

Abnormal gene expression plays key role in cancer development. A core promoter is located around the transcriptional start site. Through interaction between core promoter sequences and transcriptional factors, core promoter controls transcriptional initiation. We hypothesized that in cancer, core promoter sequences could be mutated to interfere the interaction with transcriptional factors, resulting in altered transcriptional initiation and abnormal gene expression and cancer development. We used triple-negative breast cancer (TNBC) as a model to test our hypothesis. We collected genome-wide core promoter variants from 279 TNBC genomes. After extensive filtering of normal genomic polymorphism, we identified 19,427 recurrent somatic variants in 1,238 core promoters of 1,274 genes and 1,694 recurrent germline variants in 272 core promoters of 294 genes. Many of the affected genes were oncogenes and tumor suppressors. Analysis of RNA-seq data from the same patient cohort identified increased or decreased gene expression in 439 somatic and 85 germline variants-affected genes, and the results were validated by luciferase reporter assay. By comparing with the core promoter variation data from 610 unclassified breast cancer, we observed that core promoter variants in TNBC were highly TNBC-specific. We further identified the drugs targeting the genes with core promoter variation. Our study demonstrates that core promoter is highly mutable in cancer, and can play etiological roles in TNBC and other types of cancer through influencing transcriptional initiation.

Coal Series Kaolinite (CK) is the industrial solid waste produced in coal mining and processing. CK is an indispensable raw material for new ceramics, high-end paper and advanced coatings, attribute to its advantages of pure soil quality, good wear resistance and high whiteness. China is a major kaolin producer, the coal-series kaolin reserves rank first in the world, and we need to pay attention to and solve how to effectively research and use these resources. Therefore, the introduction, main distribution, common application, main processing technology and development trend of CK are summarized. Through the comprehensive and detailed introduction, the innovative research and application of CK will be promoted.

Abstract Background Mutations in SERPINC1 lead to deficiency in antithrombin (AT) which is an endogenous anticoagulant of normal hemostasis and could result in venous thromboembolism (VTE). Case presentation A 61-year-old male patient with recurrent thrombosis returned to the hospital with multiple cerebral thrombosis after voluntary cessation of dabigatran therapy. Laboratory tests revealed a type I AT deficiency in this patient and further whole exome sequencing (WES) identified a novel heterozygous frameshift duplication (c.233_236dup, p.Val80Alafs*26) in SERPINC1 gene. Long-term dabigatran treatment was given and no recurrence or side effects were found within the followed 5 years. Conclusion A multisystem VTE patient with a novel SERPINC1 mutation (c.233_236dup, p.Val80Alafs*26) reached a favourable outcome after dabigatran treatment.

Abstract Background Many studies have shown that hypoplasia of knee bone morphology is related to the morphological features of the discoid lateral meniscus (DLM). However, few studies have focused on hypoplasia of tibial eminence morphology in juvenile patients with complete DLM. The purpose of this study was to determine the relationship between tibial eminence morphology characteristics and complete DLM in juvenile patients. Methods The DLM group comprised 34 juvenile patients with complete DLM, and the control group comprised 34 juvenile individuals, each with a normal lateral meniscus based on magnetic resonance imaging (MRI) findings. All parameters, including tibial width (TW), tibial eminence width (TEW), the height of the lateral tibial spine (HLTS), the height of the medial tibial spine (HMTS), lateral slope angle of the lateral tibial eminence (LSALTE), lateral slope angle of the medial tibial eminence (LSAMTE), tibial eminence width ratio (TEWR), height of the lateral tibial spine ratio (HLTSR), and the height of the medial tibial spine ratio (HMTSR), were recorded using coronal MR images. Statistical analyses were used to determine the differences between the two groups and whether differences were significant. Results The TEW and TEWR were significantly greater (P

Atmosphere aerosol nucleation contributes to climate change, air pollution, and human health, however the mechanisms are complex and elusive. Here the authors propose a general workflow based on deep neural network-based force field, paving the way towards fully ab initio simulation of atmospheric aerosol nucleation.

BackgroundMeasurements of IgG antibodies to wild-type SARS-CoV-2 antigens can assess vaccine efficacy, but the absolute risk of Omicron symptomatic infection at different IgG levels for children and adolescents remains uncertain, as well as the minimum effective antibody level. We sought to determine the relationship between the tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens and children with symptomatic infection of the pandemic and duration to negative conversion in China for the first time.MethodsA retrospective study was conducted, including 168 participants under 18 years old from the No.2 People’s Hospital of Lanzhou, China, diagnosed with Omicron variant BA.2.38 between July 8, 2022, and August 2, 2022. We calculated odds ratios (OR) in univariate and multivariate regression to assess the association of symptomatic infection with the tertiles of IgG, respectively. Kaplan–Meier curves and Cox proportional hazards regression were used to evaluate the relationship between IgG level and negative conversion time.ResultsThe average age of the 168 children included in this study was 7.2 (4.7) years old, 133 (79.2%) were symptomatic patients, and the average negative conversion time was 12.2 (3.5) days. The participants with high IgG levels were less likely to become symptomatic, had a shorter turnaround time, and had higher values of IgM and nucleic acid CT. Compared to those with the lowest tertile of IgG, patients with the highest tertile had a 91% lower risk of developing a symptomatic infection after fully adjusting for confounders (OR = 0.09, 95% CI, 0.02-0.36, p = 0.001). There’s no robust relationship between IgG level and negative conversion time in multivariate Cox regression.ConclusionThe risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive models.

ObjectiveTo compare the efficacy and safety of different-course corticosteroids plus mycophenolate mofetil (MMF) as maintenance therapy in autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) without tumor and explore the optimal course of corticosteroids.MethodsFifty-five patients with definite AE without tumor were enrolled consecutively between June 2015 and November 2020 and retrospectively divided three groups according to the course of treatment with corticosteroid, i.e., a group of patients with a course of 3-6 months (Group 3-6mo), 6-12 months (Group 6-12mo), and >12 months (Group >12mo). Demographic data, clinical manifestation and ancillary tests results were recorded. The dosage and courses of corticosteroid treatment, the recovery of neurological function, the occurrence of adverse effects, and relapses were followed up.ResultsA total of 55 patients were included in the final analysis. The numbers of patients in Group 3-6 mo, Group 6-12 mo, and Group >12 mo was 14, 17, and 24, respectively. A significantly higher proportion of patients in Group >12 mo showed a decreased level of consciousness at the onset (12, 50%) than in Group 3-6 mo and Group 6-12 mo (2,14.3%; 3, 17.6%) (p = 0.033). The incidence of MRI abnormalities was significantly higher in Group 6-12 mo and Group >12 mo (10, 58.8%; 16, 66.7%) than in Group 3-6 mo (3, 21.4%) (P=0.023). Ordinal regression analysis indicated that decreased level of consciousness was associated with the course of corticosteroid (OR=3.838, 95% CI: 1.103-13.323, P=0.035). No significant difference was observed between the three groups regarding the cumulative dose of corticosteroids administered during the first three months of long-term treatment (P>0.05). Additionally, no significant difference in the cumulative dosage of corticosteroids was found between patients in Group 6-12 months and Group >12 months during the first 6 months after beginning long-term treatment. The mRS scores of the three groups were not statistically significant before and after first-line treatment or at the last follow-up. Bonferroni multiple comparison test indicated that the mRS scores of patients in Group 6-12 months and Group >12 months were not statistically significant at 3 months and 12 months after the start of long-term treatment. During the follow-up, 50 (90.9%) patients achieved satisfactory neurological function (mRS score ≤2). Five patients (9.1%) experienced a first relapse and 2 of them were overlapped with both anti-NMDA receptor and glial antibodies. The incidence of adverse effects was significantly higher in Group >12 mo (17, 70.8%) than in Group 3-6 mo (3, 21.4%) and Group 6-12 mo (5, 29.4%) (P=0.003).ConclusionsThe beneficial effects of oral corticosteroid treatment may do not persist beyond 12 months and may even contribute to an increased incidence of adverse effects. In order to optimize the effectiveness and safety of treatment, we recommend a corticosteroid course of 3-12 months. Patients with reduced levels of consciousness may be more inclined to choose longer courses of corticosteroids for long-term treatment. Patients with an “overlapping syndrome” may require more intense immunotherapy to prevent relapse.

This paper proposes a fast transient load response capacitor-less low-dropout regulator (CL-LDO) for digital analog hybrid circuits in the 180 nm process, capable of converting input voltages from 1.2 V to 1.8 V into an output voltage of 1 V. The design incorporates a rail-to-rail input and push–pull output (RIPO) amplifier to enhance the gain while satisfying the requirement for low power consumption. A super source follower buffer (SSFB) with internal stability is introduced to ensure loop stability. The proposed structure ensures the steady-state performance of the LDO without an on-chip capacitor. The auxiliary circuit, or transient enhancement circuit, does not compromise the steady-state stability and effectively enhances the transient performance during sudden load current steps. The proposed LDO consumes a quiescent current of 47 µA and achieves 25 µV/mA load regulation with a load current ranging from 0 to 20 mA. The simulation results demonstrate that a settling time of 0.2 µs is achieved for load steps ranging from 0 mA to 20 mA, while a settling time of 0.5 µs is attained for load steps ranging from 20 mA to 0 mA, with an edge time of 0.1 µs.

Polycarboxylic superplasticizers (PCEs) exhibit numerous advantages as concrete additives, effectively improving the stability and strength of concrete. However, competitive adsorption of PCEs occurs in the presence of clay, which may affect the cement dispersion and water-reducing performance. Extensive research has been conducted on the physical and mechanical properties of PCEs; however, the effect of the diverse structures of PCEs on the competitive adsorption on clay and cement hydration products has been rarely studied. This study employs Ca-montmorillonite (CaMMT) as a clay representative, by constructing adsorption models of PCEs on CaMMT and cement hydration products. A comparison of the adsorption energies considering different side-chain lengths of PCEs is included. Typically, the adsorption energy on CaMMT is lower than that on hydration products, leading PCEs to preferentially adsorb on the clay, thereby reducing its effective dosage in the cement particles. The challenge of PCE adsorption on CaMMT increases with the polymerization degree, and methylallyl polyoxyethylene ether (HPEG) exhibits lower adsorption energies on CaMMT. The density of states (DOS) analysis indicated the highest peak values of allyl polyethylene ether (APEG) as well as the peak area at n (polymerization degree) = 1. The total number of transferred electrons for APEG was 0.648, surpassing those of other PCEs. The interaction mechanism of PCEs with clay and hydration products is further elucidated through electronic gain/loss analysis, also providing a basis for the theoretical analysis on how to reduce the adsorption of PCEs on clay and the structural design of mud-resistant PCEs.

Kynurenine, a tryptophan metabolite, is increased in the circulating plasma of obese individuals, but the source has been unclear. Here, the authors show in mice that mature adipocytes produce kynurenine, with vitamin B6 administration preventing accumulation and protecting against high-fat diet.

According to economists, we should think beyond the objective well-being indicators and pay more attention to the subjective well-being, agency, and capability of immigrants as the basis of immigration policy. However, few studies on the children of new immigrants in Taiwan have been conducted from the perspective of subjective well-being and agency. Since the concept of agency is still controversial, this study further considers the current research findings based on Giddens’ theory of agency and explores possible directions for future study. It was found that current studies have focused on how children of new immigrants adapt to mainstream society rather than on developing their agency. This paper proposes two concrete directions for future studies through further investigation. First is to understand, at the micro level, the problems of the social position of the new immigrant children through their embodied experience and feelings to raise their conscious reflection and achieve their subjective well-being. Second is to understand, at the meso level, the interactions of new immigrant children with specific community members in communities of practice, so as to understand their constraints and the agentic strategies they utilize, which will serve as an important reference for future educational policies and practices.

Abstract Background The purpose of this retrospective study was to investigate the determinants of postoperative respiratory failure in elderly patients with hip fracture. Methods The subjects of this study were 663 elderly patients who had hip fracture and had been treated with total hip arthroplasty at our hospital from January 2014 to May 2020. According to the occurrence of postoperative respiratory failure, 626 patients with no respiratory failure were retrospectively included in the control group, and 37 cases combined with respiratory failure were enrolled in the PRF group. The clinical and surgical data of the two groups were collected and analyzed to evaluate the determinants of respiratory failure by logistic regression analysis. Results There were no significant differences in the demographics and baseline variables including age, gender, fracture type and location between the groups (P > 0.05). All patients received hip surgery including total hip arthroplasty (THA), hemiarthroplasty (HA) and internal fixation with PFNA (proximal femoral nail anti-rotation). There were no significant differences in operative time and intraoperative blood loss between the groups (P > 0.05). However, close associations were found between pulmonary hypertension (univariate analysis: OR = 3.792, 95% CI = 1.421–10.203; multivariate analysis: OR = 1.132, 95% CI = 1.003–1.251), obstructive pulmonary disease (OR = 1.119, 95% CI = 1.009–1.238; multivariate analysis: OR = 13.298, 95% CI = 4.021–43.298), bronchiectasis and emphysema (OR = 4.949, 95% CI = 1.919–9.873; multivariate analysis: OR = 11.231, 95% CI = 187.87), and history of respiratory failure (OR = 6.098, 95% CI = 2.012–12.198; multivariate analysis: OR = 8.389, 95% CI = 2.391–21.982) with postoperative respiratory failure (P

Abstract Background Bladder cancer is one of the most mortal cancers. Bladder cancer has distinct gene expression signature, highlighting altered gene expression plays important roles in bladder cancer etiology. However, the mechanism for how the regulatory disorder causes the altered expression in bladder cancer remains elusive. Core promoter controls transcriptional initiation. We hypothesized that mutation in core promoter abnormality could cause abnormal transcriptional initiation thereby the altered gene expression in bladder cancer. Methods In this study, we performed a genome-wide characterization of core promoter mutation in 77 Spanish bladder cancer cases. Results We identified 69 recurrent somatic mutations in 61 core promoters of 62 genes and 28 recurrent germline mutations in 20 core promoters of 21 genes, including TERT, the only gene known with core promoter mutation in bladder cancer, and many oncogenes and tumor suppressors. From the RNA-seq data from bladder cancer, we observed altered expression of the core promoter-mutated genes. We further validated the effects of core promoter mutation on gene expression by using luciferase reporter gene assay. We also identified potential drugs targeting the core promoter-mutated genes. Conclusions Data from our study highlights that core promoter mutation contributes to bladder cancer development through altering gene expression.

Rapidly finding low-energy structures on high-dimensional potential energy surfaces remains a challenging problem for cluster science. We present a fast optimization method for structure prediction named mirror-rotation searching, which is inspired by the idea of symmetry and conservation. Our search algorithm can quickly converge to the minima of energy valley by continuously performing mirror-rotation transformation on the cluster, and we introduce the term vaminima to describe these minima. For the selected Lennard-Jones cluster of size N≤150, convergence to a vaminima on average takes 413 relaxations, and finding fullerene C_{60} from a random initial structure is 49-fold faster than the traditional genetic algorithm. The approach is general and flexible and can greatly improve the search efficiency of unbiased global optimization algorithms and be applied to different kinds of problems, such as molecular structure search, crystal structure prediction, and protein folding.

A dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18–55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 μg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 μg, 60 μg, and 90 μg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520)

With the rapid development and widespread application of blockchain technology in recent years, smart contracts running on blockchains often face security vulnerability problems, resulting in significant economic losses. Unlike traditional programs, smart contracts cannot be modified once deployed, and vulnerabilities cannot be remedied. Therefore, the vulnerability detection of smart contracts has become a research focus. Most existing vulnerability detection methods are based on rules defined by experts, which are inefficient and have poor scalability. Although there have been studies using machine learning methods to extract contract features for vulnerability detection, the features considered are singular, and it is impossible to fully utilize smart contract information. In order to overcome the limitations of existing methods, this paper proposes a smart contract vulnerability detection method based on deep learning and multimodal decision fusion. This method also considers the code semantics and control structure information of smart contracts. It integrates the source code, operation code, and control-flow modes through the multimodal decision fusion method. The deep learning method extracts five features used to represent contracts and achieves high accuracy and recall rates. The experimental results show that the detection accuracy of our method for arithmetic vulnerability, re-entrant vulnerability, transaction order dependence, and Ethernet locking vulnerability can reach 91.6%, 90.9%, 94.8%, and 89.5%, respectively, and the detected AUC values can reach 0.834, 0.852, 0.886, and 0.825, respectively. This shows that our method has a good vulnerability detection effect. Furthermore, ablation experiments show that the multimodal decision fusion method contributes significantly to the fusion of different modalities.

Both reticuloendotheliosis and Marek's disease are neoplastic diseases of chickens caused by reticuloendotheliosis virus (REV) and Marek's disease virus (MDV), respectively. The infection of REV or MDV may lead to clinical tumors and also result in immunosuppression and easily allow secondary infection by other pathogens. Here, we investigated a breeder flock of three-yellow chickens in southern China that had been vaccinated with CVI988/Rispens at hatching and had experienced depression, weakness, reduction in weight gain, and an increased death rate after 120 d of age. The morbidity and mortality were 20% and 10%, respectively, at 140 d of age when this infection was diagnosed. The necropsy of the birds revealed significant tumor-like lesions in the heart, liver, spleen, and ceca. Peripheral blood lymphocytes and tumor-like tissues were sampled for PCR detection and for histopathological observation, for virus isolation and the subsequent immunofluorescent assay on the cell cultures and for gene sequencing of the isolated viruses. A REV isolate GX18NNR1 and a MDV isolate GX18NNM5 were both recovered from the sampled bird. Further phylogenetic analysis based on the env gene of REV and the meq gene of MDV demonstrated that GX18NNR1 was closely related to the reference REV strain MD-2, which was isolated from a contaminated commercial turkey herpesvirus vaccine. In addition, the GX18NNM5 was found to belong to the Chinese very virulent MDV strains' cluster. The coinfection of REV and MDV may contribute to tumor outbreaks with high morbidity and mortality in three-yellow chicken flocks.

Marek's disease virus (MDV) is considered a unique member of the Alphaherpesvirinae subfamily that induces rapid onset of T cell lymphoma in chickens. Compared with other conserved UL56 gene homologues of herpesviruses, little is known about the roles of MDV UL56 gene, while recent studies of mammalian herpesvirus pUL56 proteins have revealed their involvement in promoting ubiquitination of the Nedd4 (neural precursor cell expressed developmentally down-regulated protein 4) -like E3 ubiquitin ligases for proteasomal degradation and in modulating host immune responses. To determine the expression kinetics of UL56 gene products, chicken embryo fibroblasts were infected with very virulent or attenuated MDV strain and analyzed by quantitative PCR and Western blotting. During the time course of infection, the levels of UL56 mRNA transcripts increased consistently. At the translational level, the pUL56 protein encoded by UL56 gene was expressed in the size of 32 kDa, which emerged as early as 12 h post-infection (hpi) but otherwise began to wane at 72 hpi thereafter. With the treatment of viral DNA synthesis inhibitors, the pUL56 expression was significantly reduced, featuring the dynamics of a late (γ)-gene product. By confocal imaging, pUL56 was found to reside in the Golgi compartment. Both the L-domain motifs and the C-terminal tail-anchored transmembrane were essential for its intracellular localization. Noticeably, pUL56 co-localized with a truncated mutant of the chicken Nedd4-like family protein harboring only the WW domains; however, co-immunoprecipitation assay established no direct interaction between them, and the ectopic expression of pUL56 did not alter the abundance of endogenous Nedd4-like protein. Overall, the present study provides a caveat that the pUL56 homologues of different herpesviruses with structural similarities might vary in expression patterns and probably in functional consequences. For this reason, further investigation should be encouraged to focus on the potential association between UL56 gene and MDV pathogenesis in the context of engineered viral mutants.

Abstract Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti‐programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF‐β). Using glutathione‐responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF‐β1 receptor, it is demonstrated that local inhibition of TGF‐β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long‐term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8+ cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen‐presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.

ObjectiveThis study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE).MethodsThis retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed.ResultsOf the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group (p < 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up (p < 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44–15.59, and p=0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65–47.16; and p = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups.ConclusionDisease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.

Infectious bronchitis (IB) virus (IBV) causes considerable economic losses to poultry production. The data on transmission dynamics of IBV in China are limited. The complete genome sequences of 212 IBV isolates in China during 1985–2020 were analyzed as well as the characteristics of the phylogenetic tree, recombination events, dN/dS ratios, temporal dynamics, and phylogeographic relationships. The LX4 type (GI-19) was found to have the highest dN/dS ratios and has been the most dominant genotype since 1999, and the Taiwan-I type (GI-7) and New type (GVI-1) showed an increasing trend. A total of 59 recombinants were identified, multiple recombination events between the field and vaccine strains were found in 24 isolates, and the 4/91-type (GI-13) isolates were found to be more prone to being involved in the recombination. Bayesian phylogeographic analyses indicated that the Chinese IBVs originated from Liaoning province in the early 1900s. The LX4-type viruses were traced back to Liaoning province in the late 1950s and had multiple transmission routes in China and two major transmission routes in the world. Viral phylogeography identified three spread regions for IBVs (including LX4 type) in China: Northeastern China (Heilongjiang, Liaoning, and Jilin), north and central China (Beijing, Hebei, Shanxi, Shandong, and Jiangsu), and Southern China (Guangxi and Guangdong). Shandong has been the epidemiological center of IBVs (including LX4 type) in China. Overall, our study highlighted the reasons why the LX4-type viruses had become the dominant genotype and its origin and transmission routes, providing more targeted strategies for the prevention and control of IB in China.

Abstract Background Core promoter controls transcription initiation. However, little is known for core promoter diversity in the human genome and its relationship with diseases. We hypothesized that as a functional important component in the genome, the core promoter in the human genome could be under evolutionary selection, as reflected by its highly diversification in order to adjust gene expression for better adaptation to the different environment. Results Applying the “Exome-based Variant Detection in Core-promoters” method, we analyzed human core-promoter diversity by using the 2682 exome data sets of 25 worldwide human populations sequenced by the 1000 Genome Project. Collectively, we identified 31,996 variants in the core promoter region (− 100 to + 100) of 12,509 human genes ( https://dbhcpd.fhs.um.edu.mo ). Analyzing the rich variation data identified highly ethnic-specific patterns of core promoter variation between different ethnic populations, the genes with highly variable core promoters, the motifs affected by the variants, and their involved functional pathways. eQTL test revealed that 12% of core promoter variants can significantly alter gene expression level. Comparison with GWAS data we located 163 variants as the GWAS identified traits associated with multiple diseases, half of these variants can alter gene expression. Conclusion Data from our study reals the highly diversified nature of core promoter in the human genome, and highlights that core promoter variation could play important roles not only in gene expression regulation but also in disease predisposition.

During the process of transmission and spread of avian leukosis virus subgroup J (ALV-J) in chickens worldwide, the viral genome is constantly changing. A comprehensive and systematic study of the evolutionary process of ALV-J in China is needed. In this study, we amplified the full-length viral cDNA sequences of 16 ALV-J isolates of Yellow-chicken origin and analyzed and compared these sequences with another 69 ALV-J strains isolated during the years 1988–2018. These isolates were then sorted into 2 clusters: cluster I included isolates that mainly originated from the layers and White-feather broilers from northern China; cluster II included isolates mainly from the Yellow-chicken, most of them being from southern China. According to the sequence homologies of the whole genome and gag, pol, gp85, and gp37 genes, the ALV-J strains are more likely to randomly change in different directions from the original strain HPRS-103 as time passes. The results of entropy analysis of the sequences of gag, pol, and env revealed that the env gene had the largest variation, and the gag gene nonconserved sites are mainly concentrated in p19, p10, and p12. In addition, 84.71% (72/85) of the isolates had the 205-nucleotide (nt) deletion in the 3′UTR region, and 30.59% (26/85) of the isolates had the 125-nt to 127-nt deletion in the E element. Our study provides evidence for the coexistence of 2 extremely different clusters of ALV-J prevailing in China and in some other countries during the period of 1988–2018 and implies that the clusters are highly dependent on the host genetic background and the geographic location.

Outpatient clinics’ productivity largely depends on their appointment scheduling systems. It is crucial for appointment scheduling to understand the intrinsic heterogeneity in patient and service types and act accordingly. This article describes an outpatient clinic dataset of consultation service time with heterogeneous characteristics. The dataset contains 6637 consultation records collected from 381 half-day sessions between 2018 and 2019. Each record includes encrypted session and patient IDs, consultation start and (approximated) end times, the month and day of the week, whether it was on a holiday, the patient’s visit count for a specific medical condition, gender, whether the consultation was cancer-related, and the distance from the patient’s mailing address to the clinic. These features can be used to classify patients into heterogeneous groups in studies of appointment scheduling. Therefore, this dataset with rich, heterogeneous patient characteristics provides a valuable opportunity for healthcare operations management researchers to develop, test, and benchmark the performance of their models and methods. It can also be used for studying appointment scheduling in other service industries. More generally, it provides pedagogical value in areas related to management science and operations research, applied statistics, and machine learning.

Currently, the trust mechanisms of various Internet application platforms are still built under the orders of centralized authorities. This centralized trust mechanism generally suffers from problems such as excessive power of central nodes, single point of failure and data privacy leakage. Blockchain is a new type of distributed data architecture with non-tamperability, openness and transparency, and traceability, which can achieve secure and trustworthy sharing of data without the participation of third-party authorities. The decentralized trust mechanism built based on the blockchain provides a new research paradigm with broad development prospects to solve the problem of establishing reliable information sharing under the environmental conditions of incomplete reliability in finance, healthcare, energy, and data security. In response to the issues exposed by centralized trust mechanisms in recent years, based on the critical technology of blockchain, this paper surveys the relevant literature around the vital issue of building a decentralized and secure trust mechanism. First, the decentralized trust mechanism architecture is sorted out by comparing different decentralized platforms. The blockchain is divided into the data layer, network layer, consensus layer, contract layer and application layer, which correspond to the theory, implementation, operation, extension, and application of the decentralized trust mechanism of a blockchain, a district-centric platform. Secondly, the principles and technologies of blockchain are elaborated in detail, focusing on the underlying principles, consensus algorithms, and smart contracts. Finally, blockchain problems and development directions are summarized in light of relevant literature.

The success of image classification depends on copious annotated images for training. Annotating histopathology images is costly and laborious. Although several successful self-supervised representation learning approaches have been introduced, they are still insufficient to consider the unique characteristics of histopathology images. In this work, we propose the novel histopathology-oriented self-supervised representation learning framework (HistoSSL) to efficiently extract representations from unlabeled histopathology images at three levels: global, cell, and stain. The model transfers remarkably to downstream tasks: colorectal tissue phenotyping on the NCTCRC dataset and breast cancer metastasis recognition on the CAMELYON16 dataset. HistoSSL achieved higher accuracies than state-of-the-art self-supervised learning approaches, which proved the robustness of the learned representations.

The “Two Control Zones” (TCZ) policy is the first air pollution regulation policy in China. We aim to examine the impact of the TCZ policy on green technological progress applying a difference–in–differences (DID) approach, using a city–level panel data set from 1990 to 2016. We show that the TCZ policy effectively increases the number of green patents of the cities in the two control zones. In particular, the TCZ policy has a significantly positive effect on the quantity and structure of human capital, including the number of inventors of patents and green patents, and the percentage of population with a higher education level. Moreover, the effects are heterogeneous, that is, the TCZ policy has a greater impact on the number of green patents in the control zones, where there are better R&D bases and more foreign investments.

Classical link prediction methods mainly utilize vertex information and topological structure to predict missing links in networks. However, accessing vertex information in real-world networks, such as social networks, is still challenging. Moreover, link prediction methods based on topological structure are usually heuristic, and mainly consider common neighbors, vertex degrees and paths, which cannot fully represent the topology context. In recent years, network embedding models have shown efficiency for link prediction, but they lack interpretability. To address these issues, this paper proposes a novel link prediction method based on an optimized vertex collocation profile (OVCP). First, the 7-subgraph topology was proposed to represent the topology context of vertexes. Second, any 7-subgraph can be converted into a unique address by OVCP, and then we obtained the interpretable feature vectors of vertexes. Third, the classification model with OVCP features was used to predict links, and the overlapping community detection algorithm was employed to divide a network into multiple small communities, which can greatly reduce the complexity of our method. Experimental results demonstrate that the proposed method can achieve a promising performance compared with traditional link prediction methods, and has better interpretability than network-embedding-based methods.

ABSTRACT: The reticuloendotheliosis virus (REV) and the Marek's disease virus (MDV) cause reticuloendotheliosis (RE) and Marek's disease (MD) in poultry, respectively. According to epidemiological results obtained in our laboratory from 2010 to 2017, the positive rates of REV and MDV co-infection remained at low levels. In the present study, during the period of October 2018 to July 2020, 4 clinical cases with high morbidity (5%-20%) and mortality (2%-10%), caused by the co-infection of REV and vv+ MDV-like strains, were diagnosed and analyzed by histopathological observation, cell cultures and detection with ELISA and IFA, and the PCR and by sequencing of the isolates’ genes. Sequencing and the sequence analysis on the complete genomes of the REV strains and the meq genes of the MDV strains were performed. The results, based on the complete genome, LTR, gag, pol, and env genes’ nucleotide sequences of the REV strains, showed that the REV isolates and 68.0 % (17/25) of the reference strains were in a same branch, and all had a high sequence similarity (>99.0%). The similarities between the four isolates and a vv+MDV strain GX18NNM4 were very high, up to 99.3-99.8%. Also, the amino acid residuals at locations 71, 77, 80, 115, 139, 176, and 217 were all the same as A, E, Y, A, A, R, and A, respectively, in the meq gene of the four MDV isolates. In addition, the substitutes at P176R and P217A interrupted the stretches of the proline-rich repeat PPPP, indicating that these strains belonged to the vv+ MDV-like category. Our findings indicated that the more recent and frequent reemergence of REV and the subsequent co-infection with vv+ MDV-like strain has become one of the causes of the clinical outbreaks of tumors and is undoubtedly a threat to the poultry industry in southern China.

Abstract Neuropathic pain (NP) is ranked as one of the major forms of chronic pain and emerges as a direct consequence of a lesion or disease affecting the somatosensory nervous system. Despite great advances into the mechanisms of NP, clinical practice is still not satisfactory. Fortunately, progress in elucidating unique features and multiple molecular mechanisms of long non-coding RNAs (lncRNAs) in NP has emerged in the past 10 years, suggesting that novel therapeutic strategies for pain treatment may be proposed. In this review, we will concentrate on recent studies associated with lncRNAs in NP. First, we will describe the alterations of lncRNA expression after spinal cord injury (SCI) and peripheral nerve injury (PNI), and then we illustrate the role of some specific lncRNAs in detail, which may offer new insights into our understanding of the etiology and pathophysiology of NP. Finally, we put special emphasis on the altered expression of lncRNAs in the diverse biological process of NP. Recent advances we summarized above in the development of NP may facilitate translation of these findings from bench to bedside in the future.

Diatoms can accumulate high levels of triacylglycerols (TAGs) under nitrogen depletion and have attracted increasing attention as a potential system for biofuel production. In Phaeodactylum tricornutum, a model diatom, about 40% of lipid is synthesized from the breakdown of cellular components under nitrogen starvation. Our previous studies indicated that carbon skeletons from enhanced branched-chain amino acid (BCAA) degradation under nitrogen deficiency contribute to TAG biosynthesis in P. tricornutum. In this review, we outlined the catabolic pathways of all 20 amino acids based on the genome, transcriptome, proteome, and metabolome data. The contribution of these amino acid catabolic pathways to TAG accumulation was also analyzed.