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Abstract Coal bed methane (CBM), the high-quality and efficient fuel, has caught the interest of many nations as they strive for environmentally friendly development. Therefore, the efficient exploitation and utilization of CBM has become one of the international focal research problems. A significant factor affecting the mining of CBM is coal permeability. To better capture the changes that occur during the extraction of CBM, the internal swelling coefficient of matrix (ISCM) has been gradually in permeability introduced into the permeability models, and such models have become an important type of the development of permeability models. The goal is to find out more precisely the evolution mechanism of the ISCM and its influence on the permeability models. In this paper, the selection of coal structure, determination of boundary conditions and influencing factors of permeability for were first analyzed. Then, according to the research process of ISCM, the permeability models including the ISCM were reviewed and divided into four phases: proposal phase, development phase, evaluation phase and display of internal structure phase. On the basis of the ISCM values in the current coal permeability models, the primary influencing factors and evolutionary laws of the ISCM are explored. The results obtained provide guidance for future theoretical refinement of permeability models with the ISCM.

ABSTRACT Yersinia pestis has a broad host range and has caused lethal bubonic and pneumonic plague in humans. With the emergence of multiple resistant strains and the potential for biothreat use, there is an urgent need for new therapeutic strategies that can protect populations from natural or deliberate infection. Targeting F1 has been proven to be the main strategy for developing vaccines and therapeutic antibodies, but data on anti-F1 antibodies, especially in humans, are scarce. To date, three human anti-F1 monoclonal antibodies (m252, αF1Ig2, and αF1Ig8) from naive populations have been reported. Here, we constructed an antibody library from vaccinees immunized with the plague subunit vaccine IIa by phage display. The genetic basis, epitopes, and biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. Three human mAbs, namely, F3, F19, and F23, were identified. Their biolayer responses were 0.4, 0.6, and 0.6 nm, respectively. The dissociation constants (KD) of the F1 antigen were 1 pM, 0.165 nM, and 1 pM, respectively. Although derived from distinct Ab lineages, that is, VH3-30-D3-10-JH4 (F3&F23) and VH3-43-D6-19-JH4 (F19), these mAbs share similar binding sites in F1 with some overlap with αF1Ig8 but are distinct from αF1Ig2. Each of them provided a significant protective effect for Balb/c mice against a 100 median lethal dose (MLD) challenge of a virulent Y. pestis strain when administered at a dose of 100 µg. No synergistic or antagonistic effects were observed among them. These mAbs are novel and excellent candidates for further drug development and use in clinical practice.IMPORTANCEIn this study, we identified three human monoclonal antibodies with a high affinity to F1 protein of Yersinia pestis. We discovered that they have relatively lower somatic hypermutations compared with antibodies, m252, αF1Ig2, and αF1Ig8, derived from the naive library reported previously. We also observed that these mAbs share similar binding sites in F1 with some overlapping with αF1Ig8 but distinct from that of αF1Ig2. Furthermore, each of them could provide complete protection for mice against a lethal dose of Yersinia pestis challenge. Our data provided new insights into the anti-F1 Ab repertories and their associated epitopes during vaccination in humans. The findings support the additional novel protective human anti-F1Abs for potential therapeutics against plaque.

BackgroundMigraine, a neurological condition perpetually under investigation, remains shrouded in mystery regarding its underlying causes. While a potential link to Right-to-Left Shunt (RLS) has been postulated, the exact nature of this association remains elusive, necessitating further exploration.MethodsThe amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and functional connectivity (FC) were employed to investigate functional segregation and functional integration across distinct brain regions. Graph theory-based network analysis was utilized to assess functional networks in migraine patients with RLS. Pearson correlation analysis further explored the relationship between RLS severity and various functional metrics.ResultsCompared with migraine patients without RLS, patients with RLS exhibited a significant increase in the ALFF within left middle occipital and superior occipital gyrus; In migraine patients with RLS, significantly reduced brain functional connectivity was found, including the connectivity between default mode network and visual network, ventral attention network, as well as the intra-functional connectivity of somatomotor network and its connection with the limbic network, and also the connectivity between the left rolandic operculum and the right middle cingulate gyrus. Notably, a significantly enhanced functional connectivity between the frontoparietal network and the ventral attention network was found in migraine with RLS; Patients with RLS displayed higher values of the normalized clustering coefficient and greater betweenness centrality in specific regions, including the left precuneus, right insula, and right inferior temporal gyrus. Additionally, these patients displayed a diminished nodal degree in the occipital lobe and reduced nodal efficiency within the fusiform gyrus; Further, the study found positive correlations between ALFF in the temporal lobes, thalamus, left middle occipital, and superior occipital gyrus and RLS severity. Conversely, negative correlations emerged between ALFF in the right inferior frontal gyrus, middle frontal gyrus, and insula and RLS grading. Finally, the study identified a positive correlation between angular gyrus betweenness centrality and RLS severity.ConclusionRLS-associated brain functional alterations in migraine consisted of local brain regions, connectivity, and networks involved in pain conduction and regulation did exist in migraine with RLS.

Soil water is the main water source for plants, which is replenished by rainfall in the water-limited agricultural systems. Quantifying temporal dynamics of water soil deficit and its replenishment by rainfall can evaluate whether soil water meet the water demand for plants. This would provide accurate guide for when and how the irrigation practices conducted. However, this topic has not been deeply elucidated. In this study, soil water content at varied soil depths and precipitation were continuously monitored during two growing seasons in an apple orchard in the Loess Plateau of China. Soil water storage, soil water deficit and replenishment were also quantified. The results showed that soil water content varied temporally due to the impacts of rainfalls. Soil water storage at 0 ~ 200 cm depth ranged from 272.5 mm to 355.6 mm and the degree of soil water deficit ranged from 0.34 to 0.53 correspondingly. Meanwhile, replenishment of soil water by rainfall was 13.00% in 2017 and 9.78% in 2018, respectively. The qualitative relationship between monthly rainfalls and replenishment indicated that soil water was replenished by rainwater only at soil layers shallower than 160 cm. From the temporal dynamics of soil water content and deficit conditions, soil water could meet the water demand at the fruit expanding stage of apple trees. Irrigation measures should be taken to reduce the soil drought stress at this stage. This study provided an effective hydrological basis to improve the irrigation management of orchards and the efficiency of water resource.

Cigarette smoke clumping, an important indicator of smoke status, draws consumer attention due to its correlation with smoke concentration, thickness, fullness, and the clumping index, which significantly affects the sensory quality of cigarettes. Due to the difference of individuals and the influence of environment, the current manual evaluation method is greatly influenced by subjectivity, and the consistency and reproducibility of the evaluation results are poor. In order to solve this problem, this study takes clusteriness as a breakthrough point in the digital research of sensory evaluation. Firstly, the best-selling cigarettes are selected as the research object to form a consistent evaluation of clusteriness through expert evaluation. Then, from the microscopic point of view, that is, the particle size distribution of flue gas, the influence degree of flue gas clumping is explored. In the experiment, the diameter particle spectrometer was used to detect the aerosol diameter particles, and the characteristics of the diameter particle distribution curve, including the spectral shape area, the spectral peak intensity and the mean width, were further verified, and the correlation was proved. Finally, a model of granularity distribution and cluster relationship is constructed based on the feature engineering method, and the expert evaluation score is used as the expected value of the model for training, and finally the cluster digital evaluation system is realized.

ABSTRACT Importance Preserving skin health is crucial for atopic dermatitis control as well as for the thriving of children. However, a well‐developed and validated tool that measures the knowledge, attitude, and practice of skin care is lacking. Objective To develop and validate the atopic dermatitis and infant skincare knowledge, attitude, and practice (ADISKAP 1.0) scale that measures parental health literacy on atopic dermatitis and skin care. Methods We conducted a review of the literature, a focus group (two dermatologists and 12 parents), and a panel discussion in order to generate the ADISKAP prototype. Two samples of parents with knowingly superior (dermatologists, n = 59) and inferior (general population, n = 395) knowledge traits participated in the validation of ADISKAP. Cronbach's alpha was reported as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess the test‐retest validity. The known‐groups technique was used to evaluate construct validity. Results The ADISKAP scale contained 17 items after content and face validity validation. After removing items that displayed poor test‐retest reliability (n = 4) and construct validity (n = 3), 12 items were retained in the ADISKAP 1.0. Interpretation ADISKAP 1.0 is a reliable and valid tool for assessing parental knowledge, attitude, and practice on infantile atopic dermatitis and skin care.

Detecting defects on a steel surface is crucial for the quality enhancement of steel, but its effectiveness is impeded by the limited number of high-quality samples, diverse defect types, and the presence of interference factors such as dirt spots. Therefore, this article proposes a fine-tuned deep learning approach to overcome these obstacles in unstructured few-shot settings. Initially, to address steel surface defect complexities, we integrated a serial multi-scale attention mechanism, concatenating attention and spatial modules, to generate feature maps that contain both channel information and spatial information. Further, a pseudo-label semi-supervised learning algorithm (SSL) based on a variant of the locally linear embedding (LLE) algorithm was proposed, enhancing the generalization capability of the model through information from unlabeled data. Afterwards, the refined model was merged into a fine-tuned few-shot object detection network, which applied extensive base class samples for initial training and sparsed new class samples for fine-tuning. Finally, specialized datasets considering defect diversity and pixel scales were constructed and tested. Compared with conventional methods, our approach improved accuracy by 5.93% in 7-shot detection tasks, markedly reducing manual workload and signifying a leap forward for practical applications in steel defect detection.

Exploring the relationship and driving forces between supply–demand of ecosystem services (ESs) and urbanization can help solve the environmental problems and promote regional sustainable development. This study analyzed the spatio-temporal distribution characteristics of supply–demand of ESs and comprehensive urbanization level (CUL) in Shaanxi Province from 2010 to 2019 and assessed the coupling relationship between ecosystem service supply–demand ratio (ESSDR) and CUL using the coupling coordination degree (CCD) model. Random forests and geographically weighted regression methods were utilized to characterize the contribution and spatial distribution of the drivers of CCD. The results showed that: (1) except for habitat quality, the ESSDR of the other three types of services as well as the comprehensive services showed a decreasing trend, CUL exhibited increasing trend; (2) Although CCD was generally increasing, a significant portion (78.51%) of regions still remained uncoordinated, with relatively better coordination shown around the Guanzhong urban agglomeration, which has a higher urbanization level; (3) The CCD in Shaanxi Province was primarily influenced by local financial income, the secondary industry, and temperature forces. In regions with high and increasing CCD, the tertiary industry was the decisive force. In other areas, there were significant spatial variations in the driving forces. These findings provide a coupled and coordinated perspective for urban ecological management, which can provide scientific reference and practical guidance for cities with different development modes.

Abstract Multimodal abstractive summarisation (MAS) aims to generate a textual summary from multimodal data collection, such as video‐text pairs. Despite the success of recent work, the existing methods lack a thorough analysis for consistency across multimodal data. Besides, previous work relies on the fusion method to extract multimodal semantics, neglecting the constraints for complementary semantics of each modality. To address those issues, a multilayer cross‐fusion model with the reconstructor for the MAS task is proposed. Their model could thoroughly conduct cross‐fusion for each modality via layers of cross‐modal transformer blocks, resulting in cross‐modal fusion representations with consistency across modalities. Then the reconstructor is employed to reproduce source modalities based on cross‐modal fusion representations. The reconstruction process constrains the fusion representations with the complementary semantics of each modality. Comprehensive comparison and ablation experiments on the open domain multimodal dataset How2 are proposed. The results empirically verify the effectiveness of the multilayer cross‐fusion with the reconstructor structure on the proposed model.

Ecological restoration is the guarantee of regional ecological security. Accurate identification of restoration areas is crucial for planning ecological programs. However, the question of how to recognize the range of restoration areas at the pixel scale in order to improve restoration efficiency still requires further discussion. In this study, a framework that integrates ecological security and feasibility of restoration through multi-criteria decision analysis was developed to identify the ecological restoration priority areas (ERPAs) in the Qinghai-Tibet Plateau (QTP). The results showed that areas with low ecological security accounted for 58.33 % of the QTP, primarily concentrated in the northwest. Areas that were feasible to be restored, represented 26.11 % of the QTP. The relatively high feasibility areas (F > 0.6) were mainly located in the northern and southwestern of the QTP, covering 23.88 % of the total feasible areas. This study ultimately identified 6.69 × 105 km2 of ERPAs, encompassing 26.05 % of the QTP. The high-priority areas were concentrated in the southwest and scattered in the northern part of the study area, accounting for 21.47 % of the ERPAs. The low-priority areas with the largest proportion (57.77 % of ERPAs) were widely distributed in the eastern part of the study area. Therefore, more attention should be paid to the southwestern region of the QTP in the subsequent ecological restoration efforts. The framework, which takes into consideration ecological security and restoration feasibility, can significantly enhance the spatial accuracy of ecological restoration area identification, providing a practical reference for further environmental optimization.

Purpose This study intends to investigate the correlation between blood pressure variability (BPV) levels and the use of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal microvasculature in hypertensive patients. Methods All individuals in the study had 24-hour ambulatory blood pressure monitoring and bilateral OCT and OCTA exams, and only data from the right eye were analyzed statistically. Results The study included 170 individuals, with 60 in the control group. The experimental group was separated into two groups based on the average real variability (ARV) median, with 55 in the low ARV group and 55 in the high ARV group. The mean thicknesses of the Retinal Nerve Fiber Layer (RNFL), internal limiting membrane-retinal pigment epithelial cell layer (ILM-RPE), vessel density (VD), and perfusion density (PD) in the high-ARV group were substantially lower in the low-ARV and control groups (p＜0.05). Multiple linear regression analysis revealed that disease duration, age, and 24 h diastolic standard deviation all affected RNFL mean thickness (p＜0.05). VD and PD were influenced by disease duration, systolic-ARV, daytime systolic blood pressure, intraocular pressure(IOP), and best-corrected visual acuity (BCVA) (p＜0.05). And the change in VD was connected to best-corrected visual acuity. Conclusion Hypertensive retinopathy is related to BPV. In clinical practice, we can assess the degree of BPV and retinopathy in hypertensive patients to track the progression of hypertension-mediated organ damage (HMOD). Correction of BPV may help treat or postpone the progression of HOMD.

The rotary energy recovery device (RERD) plays an important role in reverse osmosis (RO) desalination; however, few investigations on the formation and influence of lateral force on the RERD rotor have been published. The transient characteristics of lateral force and its relationship with pressure distribution and fluctuation in the clearance were analyzed via computational fluid dynamics (CFD) simulation. The clearance pressure distribution and lateral force were quantified under different working conditions. The eccentricity of the rotor, resistance torque and decrease in the rotary speed due to the lateral force were simulated and they were found to change with flow rate and pressure of high-pressure outlet (PHO). A new rotary speed prediction method including the effect of PHO was developed. With the increasing flow rate or PHO, the stability of RERD declined. A design optimization direction was proposed. The variation trends of rotary speed, pressure in the clearance and its fluctuation were verified through experiment. This research provides an explanation why in practice the rotary speed decreases with increasing pressure. The conclusions obtained herein can be of great significance for future research on improving the stability and lifespan and reducing the maintenance consumption of RERD.

Summary: Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called LHX1-DT, which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene. Our findings demonstrated that LHX1-DT is nuclear-localized and transiently elevated expression along with LHX1 during early differentiation of cardiomyocytes. The phenotype was rescued by overexpression of LHX1 into the LHX1-DT−/− hESCs, indicating LHX1 is the downstream of LHX1-DT. Mechanistically, we discovered that LHX1-DT physically interacted with RNA/histone-binding protein PHF6 during mesoderm commitment and efficiently replaced conventional histone H2A with a histone variant H2A.Z at the promoter region of LHX1. In summary, our work uncovers a novel lncRNA, LHX1-DT, which plays a vital role in mediating the exchange of histone variants H2A.Z and H2A at the promoter region of LHX1.

Food safety has become a subject of major concern in controlling food contamination and supervision. Effective detection and analysis methods need to be urgently exploited to cope with this grand global challenge. Among conventional methods for food safety analysis, enzyme-based biosensing methods serve a critical role in the monitoring of food safety. However, some long-lasting challenges, like high cost and low stability, hinder enzyme-based biosensing systems. In this regard, nanozymes with superior enzyme-like activity and special physical and chemical characteristics gradually emerge as excellent tools for quality and safety analysis in agricultural fields. In this review, recent advances made in the food safety analysis based on nanozymes are summarized. Firstly, an introduction of nanozymes containing their definition, classification, and modulation is provided. Subsequently, four main sensing modes used in nanozyme-based biosensing are discussed in detail. Taking advantage of nanozyme-based biosensing platforms, great achievements made in food safety are highlighted, where biological hazards, heavy metal ions, antibiotics, pesticide residues, and additives are involved. At last, personal views of the progress and perspective in this evolving field are proposed. This review not only shows great reference significance for the construction and application of nanozyme-based analysis methods but also promotes solutions to some challenges existing in food safety.

Summary: The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.

Selective adsorption is an effective method to achieve in the recovery of CV. We report that InVO4 is highly selective adsorbent for Crystal Violet (CV) from the water, which has much larger adsorption capacity (134.25 mg/g) than that of titanium dioxide, alumina, and silica gel (6.1–33.9 mg/g) although the specific surface areas of these solids are much larger than that of InVO4. The (200) facets of InVO4 exhibited the optimal sites for the selective-chemisorption of CV. The trigonal planar CV molecules are bonded to the (200) facets at all three vertices via a cationic quaternary amine and two tertiary amines. This adsorption mechanism mainly involved the formation of hydrogen-bonded water bridges (CV-N···H-O-H···O-VO3-In) on the basis of in-situ Fourier transform infrared (In-situ-FTIR). This study not only provides a new preparation method for vanadate adsorbent, but also provides a new idea for the recovery and utilization of CV in waste liquid.

As a typical ecological fragile zone and an area with a high intensity of human activities, the Loess Plateau (LP) of China has significantly altered its ecosystem and the corresponding services under the influence of urbanization processes. However, most existing studies focus on the spatial and temporal changes of ecosystem services (ESs) and their interrelationships under the influence of ecological restoration works in the LP, leaving limited research on the impacts of urbanization on ESs. Therefore, this study constructed a research framework for exploring the spatio-temporal dynamics and interactions of ESs under the influence of urbanization based on time series data from 2000 to 2020. The results showed that: (1) based on the comprehensive urbanization level (CUL), developed and developing areas accounted for 5.63% of the total area; (2) for the whole LP, all ESs except Habitat Quality (HQ) showed an increased trend. HQ showed a trade-off with the other services, while there was a clear synergy between the other three types of services; (3) in terms of processes of urbanization, Carbon Sequestration, Water Yield and HQ gradually decreased with increased levels of urbanization, and Soil Conservation increased the least in developing areas. The trade-off between HQ and the other three services decreased with increasing urbanization, while the synergy between the other three services strengthened as urbanization deepened. These findings suggest that urbanization significantly impacts ESs. It is necessary to implement appropriate measures (e.g., sponge city construction, urban green space, etc.) to address the impacts of urbanization on ESs.

Abstract Background The FAST study identified claudin-18 (CLDN18.2) as a promising novel therapeutic target for gastric cancer (GC). However, the tumor immune microenvironment and clinicopathological features of CLDN18.2-positive GC are unclear, making it difficult to develop and optimize CLDN18.2-targeted treatments. Methods This study included 80 GC patients, 60 of whom received anti-PD-1/PD-L1 treatment. CD4/CD8/CD20/CD66b/CD68/CD163/PD-1/PD-L1/TIM-3/LAG-3/FoxP3/CTLA-4/HLA-DR/STING, and CLDN18.2 were labeled using multiplex immunohistochemistry (m-IHC) to decipher the rate and spatial distribution of T cells, B cells, macrophages, and neutrophils in formalin-fixed, paraffin-embedded tumor tissues isolated from these patients. Tumor immune-microenvironmental features and patient survival stratified by CLDN18.2 expression were analyzed using two independent-sample t-tests and log-rank tests, respectively. Results We considered moderate-to-strong CLDN18.2 expression ≥ 40% of tumor cells as the cut-off for positivity. The proportion of CD8+PD-1−, CD8+LAG-3−, and CD8+TIM-3− T cells was significantly higher in CLDN18.2-positive tumors than in negative tumors (0.039 vs. 0.026, P = 0.009; 0.050 vs.0.035, P = 0.024; 0.045 vs. 0.032, P = 0.038, respectively). In addition, the number of neutrophils (CD66b+) was higher in the CLDN18.2-positive group than in the negative group (0.081 vs. 0.055, P = 0.031, respectively), while the rates of M1 (CD68+CD163−HLA-DR+), M2 macrophages (CD68+CD163+HLA-DR−), and B cells (CD20+) were comparable between the CLDN18.2-positive and negative groups. The average numbers of CD8+PD-1−, CD8+LAG-3−, and CD8+TIM-3−T cells surrounding tumor cells within a 20-μm range were higher in CLDN18.2-positive tumors than in the CLDN18.2-negative tumors (0.16 vs. 0.09, P = 0.011; 0.20 vs. 0.12, P = 0.029; 0.18 vs. 0.12, P = 0.047, respectively). In addition, in the CLDN18.2-positive group, tumor cells surrounded by CD8+PD-1−, CD8+LAG-3− T cells, or M1 macrophages within a 20-μm range accounted for a higher proportion of all tumor cells than those in the CLDN18.2-negative group (10.79% vs. 6.60%, P = 0.015; 12.68% vs. 8.70%, P = 0.049; 9.08% vs. 6.56%, P = 0.033, respectively). These findings suggest that CLDN18.2-positive GC harbors complex immune-microenvironmental features. Additionally, CLDN18.2-positive group had shorter OS and irOS than CLDN18.2-negative group (median OS: 23.33 vs.36.6 months, P

Abstract We present an analytic solution for accretion of a gaseous medium with adiabatic equation of state onto a charged dilaton black hole which moves at a constant velocity. We determine the four-velocity of accreted flow and find that it possesses axial symmetry. We obtain the particle number density and the accretion rate which depend on the mass, the magnetic charge, and the dilation of black hole, meaning that these parameters take important roles in the process of accretion. Possible theoretical and observational constraints on the parameter related to the dilation are discussed. The results may help us to get deeper understanding of the behavior of accreted flow near the event horizon of black hole.

Video anomaly event detection (VAED) is one of the key technologies in computer vision for smart surveillance systems. With the advent of deep learning, contemporary advances in VAED have achieved substantial success. Recently, weakly supervised VAED (WVAED) has become a popular VAED technical route of research. WVAED methods do not depend on a supplementary self-supervised substitute task, yet they can assess anomaly scores straightway. However, the performance of WVAED methods depends on pretrained feature extractors. In this paper, we first address taking advantage of two pretrained feature extractors for CNN (e.g., C3D and I3D) and ViT (e.g., CLIP), for effectively extracting discerning representations. We then consider long-range and short-range temporal dependencies and put forward video snippets of interest by leveraging our proposed temporal self-attention network (TSAN). We design a multiple instance learning (MIL)-based generalized architecture named CNN-ViT-TSAN, by using CNN- and/or ViT-extracted features and TSAN to specify a series of models for the WVAED problem. Experimental results on publicly available popular crowd datasets demonstrated the effectiveness of our CNN-ViT-TSAN.

ABSTRACT Importance Patients with atopic dermatitis (AD) display compromised epidermal barrier and suffer from poor quality of life. We hypothesized that quality of life could reflect in the changes in the epidermal barrier function. Objective To determine whether the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with AD. Methods A total of 120 children, aged 0–12 years, with moderate AD were enrolled. Children were topically treated with topical corticosteroids (TCS) and an emollient for 2 weeks. The Eczema Area and Severity Index (EASI), visual analogue scale (VAS) for pruritus severity, the Infant’s Dermatitis Quality of Life Index (IDQOL) and the Children’s Dermatology Life Quality Index (CDLQI) were evaluated. Transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration, and skin surface pH were measured. Correlations of epidermal barrier function with pruritus, life quality, and EASI were determined. Results Following 2‐week treatments, significant improvements were observed in EASI, TEWL, SC hydration, the VAS of pruritus, as well as DQOL (P < 0.001 for all). TEWL positively, while SC hydration negatively correlated with VAS pruritus, DQOL, and EASI (P < 0.001). Interpretation Both TEWL and SC hydration levels can serve as indicators of the severity of pruritus and quality of life in children with AD.

Rapid identification of many industrial material parts is the key to effectively improving the efficiency of the industrial production process and intelligent warehousing. Accurate identification of both similar and special parts is an important problem. In this paper, a multi-side joint industrial part recognition method based on model fusion learning is proposed. A multi-channel visual acquisition system is designed to construct a fast industrial part data set with time and space consistency. Two joint identification methods for multi-side acquisition are proposed, and the classification results are fused to improve the model’s accuracy and solve the classification problem for similar parts. The experimental results show that compared with the traditional model, the prediction accuracy of the multi-channel multi-input model proposed in this paper is improved by approximately 6%, and the accuracy of the single-channel multi-input model is improved by approximately 10%. The accuracy of part recognition is far better than that of the traditional model, and it therefore provides a new strategy for the rapid training and recognition of industri-al parts in intelligent storage.

Abstract Background To evaluate the efficacy and safety of different intravitreal corticosteroids for treating diabetic macular edema (DME). Methods Four databases were systematically searched for randomized controlled trials comparing different intravitreal corticosteroids for treating DME. The primary outcome was the change in best-corrected visual acuity (BCVA) within 6 months after the first injection (short-term BCVA). Secondary outcomes were the change in BCVA over 1 year (long-term BCVA) and changes in central macular thickness (CMT) and intraocular pressure (IOP) within 6 months after the first injection. Network meta-analysis was performed to aggregate the results from the individual studies. Results Nineteen trials involving 2839 eyes were included. Intravitreal triamcinolone acetonide (TA) injections (≥ 8 mg and 4–8 mg), fluocinolone acetonide (FA) implants (0.5 µg/day) and dexamethasone (DEX) implants (700 µg) improved short-term BCVA (mean changes in logMAR [95% confidence interval] − 0.27 [− 0.40, − 0.15]; − 0.12 [− 0.18, − 0.06]; − 0.10 [− 0.21, − 0.01]; and − 0.06 [− 0.11, − 0.01]). Intravitreal TA injections (4 mg, multiple times), FA implants (0.5 µg/day and 0.2 µg/day), and DEX implants (350 µg) improved long-term BCVA (mean changes in logMAR [95% confidence interval] − 0.11 [− 0.21, − 0.02]; − 0.09 [− 0.15, − 0.03]; − 0.09 [− 0.14, − 0.02]; and − 0.04 [− 0.07, − 0.01]). All intravitreal corticosteroids reduced CMT, and different dosages of TA did not show significant differences in increasing IOP. Conclusions Intravitreal corticosteroids effectively improved BCVA in DME patients, with higher dosages showing greater efficacies. TA was not inferior to FA or DEX and may be considered a low-cost alternative choice for DME patients. The long-term efficacy and safety of different corticosteroids deserve further investigation. Trial registration Prospectively registered: PROSPERO, CRD42020219870

The landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing is rapidly evolving. While serology testing has limited diagnostic capacity for acute infection, its role in providing population-based information on positivity rates and informing evidence-based decision making for public health recommendations is increasing. With the global availability of vaccines, there is increasing pressure on clinical laboratories to provide antibody screening and result interpretation for vaccinated and non-vaccinated individuals. Here we present the most up-to-date data on SARS-CoV-2 antibody timelines, including the longevity of antibodies, and the production and detection of neutralizing antibodies. Additionally, we provide practical guidance for clinical microbiology laboratories to both verify commercial serology assays and choose appropriate testing algorithms for their local populations.

Graphene oxide is attractive in flexible materials due to its biocompatibility. Herein, flexibility of graphene oxide under uniaxial tensile strain has been studied in term of the bending modulus. It is demonstrated that tensile strain plays an effective role in softening the bending modulus of graphene oxide. The strained graphene oxide can be even more flexible than graphene. The mechanism of strain softened bending modulus is discussed where weakened atomic bonding accounts directly for the enhanced flexibility. Particularly, an important factor for softened bending modulus is proposed, i.e. alignment of epoxide groups. The degradation of bending modulus is more prominent when the epoxides are aligned along the bending direction. This work not only proposes an effective method to enhance the flexibility of graphene oxide, but also unveils the mechanism of softened bending modulus, which could be useful in design of highly flexible materials.

Abstract Zigzag molecular belts have captured the imagination of scientists for over a half century because of their aesthetically appealing structures and tantalizing properties. One of the formidable challenges in synthesis is to circumvent the energy accumulated in the construction of strained structures. Reported herein is our theoretical study to quantify the molecular strain energies. A general exponential function equation E strain = a·n·e −n/b was obtained to estimate strain energies of both conjugated and partially hydrogenated hydrocarbon belts and their heteroatom-embedded analogs. The deformation of aromatic rings from planarity was revealed to contribute dominantly to the high strain energies. The method enabled the convenient quantification of the energetics of aromatization processes from partially hydrogenated double-stranded macrocycles, and facilitated the design and optimization of practical routes to synthesize the long-awaited zigzag molecular belts.

Abstract Although nanozymes have been widely developed, accurate design of highly active sites at the atomic level to mimic the electronic and geometrical structure of enzymes and the exploration of underlying mechanisms still face significant challenges. Herein, two functional groups with opposite electron modulation abilities (nitro and amino) were introduced into the metal–organic frameworks (MIL-101(Fe)) to tune the atomically dispersed metal sites and thus regulate the enzyme-like activity. Notably, the functionalization of nitro can enhance the peroxidase (POD)-like activity of MIL-101(Fe), while the amino is poles apart. Theoretical calculations demonstrate that the introduction of nitro can not only regulate the geometry of adsorbed intermediates but also improve the electronic structure of metal active sites. Benefiting from both geometric and electronic effects, the nitro-functionalized MIL-101(Fe) with a low reaction energy barrier for the HO* formation exhibits a superior POD-like activity. As a concept of the application, a nitro-functionalized MIL-101(Fe)-based biosensor was elaborately applied for the sensitive detection of acetylcholinesterase activity in the range of 0.2–50 mU mL−1 with a limit of detection of 0.14 mU mL−1. Moreover, the detection of organophosphorus pesticides was also achieved. This work not only opens up new prospects for the rational design of highly active nanozymes at the atomic scale but also enhances the performance of nanozyme-based biosensors.

Mono-/multivalent ion-selective separation has become a common requirement at the water-energy nexus, including energy storage and conversion, water purification, and sustainable industrial processes. In this review, we summarize the theory of ion transport through membrane and mechanisms of selective ion separation in nanofiltration (NF) briefly. Recent advancing in improving the mono-/multivalent ion selectivity of thin-film composite (TFC) NF membrane via size sieving enhancement, electric charge property regulation and co-enhancement of size sieving and electric charge properties are concluded. What's more, three material classes—surface assembly materials, nanomaterials and biomimetic ion channels are highlighted as candidates for the preparation of ion-selective NF membranes. Lastly, design directions and critical challenges for developing high-selectivity nanofiltration membranes based on the ion-selective mechanisms are provided.

Immune characteristics were reported correlated to benefit neoadjuvant chemotherapy (NAC) in breast cancer, yet integration of comprehensive genomic alterations and T-cell receptors (TCR) to predict efficacy of NAC needs further investigation. This study simultaneously analyzed TMB (Tumor Mutation Burden), TCRs, and TILs (tumor infiltrating lymphocyte) in breast cancers receiving NAC was conducted in a prospective cohort (n = 22). The next-generation sequencing technology-based analysis of genomic alterations and TCR repertoire in paired breast cancer samples before and after NAC was conducted in a prospective cohort (n = 22). Fluorescent multiplex immunohistochemistry was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in those paired samples. TMB in pretreatment tumor tissues and TCR diversity index are higher in non-pCR patients than in pCR patients (10.6 vs. 2.3; p = 0.043) (2.066 vs. 0.467; p = 0.010). TMB and TCR diversity index had linear correlation (y = 5.587x − 0.881; r = 0.522, p = 0.012). Moreover, infiltrating T cells are significantly at higher presence in pCR versus non-pCR patients. Dynamically, the TMB reduced significantly after therapy in non-pCR patients (p = 0.010) but without TCR index change. The CDR3 peptide AWRSAGNYNEQF is the most highly expressed in pre-NAC samples of pCR patients and in post-NAC samples of non-pCR patients. In addition to pCR, high clonality of TCR and high level of CD8+ expression are associated with disease-free survival (DFS). TCR index and TMB have significant interaction and may guide neo-adjuvant treatment in operable breast cancers. Response to NAC in tumors with high TCR clonality may be attributable to high infiltration and expansion of tumor-specific CD8 positive effector cells.

With accelerated urbanization and rapid expansion of the urban population, there is an increasing demand among urban residents for urban green spaces (UGS) and the ecosystem services (ES) they provide. The existing research mostly focuses on the spatial pattern of UGS types and ES provided by different UGS but ignores that residents’ preferences for UGS types and their ecological and social services should also be incorporated into the spatial planning decision-making of UGS. A web-based questionnaire was distributed randomly in urban areas of China and 1050 valid samples were collected in this study. Descriptive statistical analysis methods, structural equation modeling, and Pearson correlation were used to parse the residents’ preference for both UGS types, ecological–social services, and the relevant impact factors. The results showed that: (1) the strongest preference of residents for UGS and their ecological and social services are the attached green space, “beautifying the city”, and “physical and mental relaxation”, respectively; (2) the leading factors for residents’ access to UGS are “age” and “sufficient time”, except for attached green space. The most significant effect on both ecological and social services is the “season” factor. Further, “social gathering” and “exercise” are the services most and least likely to be affected. (3) Future planning of UGS should reinforce construction of attached green space and improve the aesthetics-related ES they provide. Construction of park green space and plaza green space should be enhanced to deal with the aging trend in society. Further, maintaining the existing construction of attached green space and building regional green space are crucial to the sustainability of UGS and its ecological–social services.

Abstract An integrated system has been provided with a-Si/H solar cells as energy conversion device, NiCo2O4 battery-supercapacitor hybrid (BSH) as energy storage device, and light emitting diodes (LEDs) as energy utilization device. By designing three-dimensional hierarchical NiCo2O4 arrays as faradic electrode, with capacitive electrode of active carbon (AC), BSHs were assembled with energy density of 16.6 Wh kg–1, power density of 7285 W kg–1, long-term stability with 100% retention after 15,000 cycles, and rather low self-discharge. The NiCo2O4//AC BSH was charged to 1.6 V in 1 s by solar cells and acted as reliable sources for powering LEDs. The integrated system is rational for operation, having an overall efficiency of 8.1% with storage efficiency of 74.24%. The integrated system demonstrates a stable solar power conversion, outstanding energy storage behavior, and reliable light emitting. Our study offers a precious strategy to design a self-driven integrated system for highly efficient energy utilization.

Abstract Background Pingdingshan City has unique and rich ecotourism landscape. To realize the sustainable development of ecotourism industry in Pingdingshan and simultaneously achieve economic development and environmental protection in the development of ecotourism resources, literature analysis and field investigation methods were used to deeply explore the advantages and problems of Pingdingshan in the process of resources development in this study. Then, the indicator system of environmental carrying capacity of Pingdingshan was established and environmental carrying capacity was calculated to understand the local tourism environmental carrying capacity. Results The development of ecotourism resources in Pingdingshan has advantages of natural conditions, convenient transportation, and sound infrastructure, but there were also problems, such as insufficient resources protection and unscientific management system. After calculation, it was found that the environmental carrying capacity of ecotourism in Pingdingshan was overloaded. Conclusion This study reveals the development of the tourism industry in Pingdingshan and provides a basis for the future development of Pingdingshan tourism resources, which is beneficial to the sustainable development of the local ecotourism industry.

Mobile edge computing (MEC) has shown tremendous potential as a means for computationally intensive mobile applications by partially or entirely offloading computations to a nearby server to minimize the energy consumption of user equipment (UE). However, the task of selecting an optimal set of components to offload considering the amount of data transfer as well as the latency in communication is a complex problem. In this paper, we propose a novel energy-efficient deep learning based offloading scheme (EEDOS) to train a deep learning based smart decision-making algorithm that selects an optimal set of application components based on remaining energy of UEs, energy consumption by application components, network conditions, computational load, amount of data transfer, and delays in communication. We formulate the cost function involving all aforementioned factors, obtain the cost for all possible combinations of component offloading policies, select the optimal policies over an exhaustive dataset, and train a deep learning network as an alternative for the extensive computations involved. Simulation results show that our proposed model is promising in terms of accuracy and energy consumption of UEs.

Face inpainting aims to repaired damaged images caused by occlusion or cover. In recent years, deep learning based approaches have shown promising results for the challenging task of image inpainting. However, there are still limitation in reconstructing reasonable structures because of over-smoothed and/or blurred results. The distorted structures or blurred textures are inconsistent with surrounding areas and require further post-processing to blend the results. In this paper, we present a novel generative model-based approach, which consisted by nested two Generative Adversarial Networks (GAN), the sub-confrontation GAN in generator and parent-confrontation GAN. The sub-confrontation GAN, which is in the image generator of parent-confrontation GAN, can find the location of missing area and reduce mode collapse as a prior constraint. To avoid generating vague details, a novel residual structure is designed in the sub-confrontation GAN to deliver richer original image information to the deeper layers. The parent-confrontation GAN includes an image generation part and a discrimination part. The discrimination part of parent-confrontation GAN includes global and local discriminator, which benefits the reconstruction of overall coherency of the repaired image while obtaining local details. The experiments are executed over the publicly available dataset CelebA, and the results show that our method outperforms current state-of-the-art techniques quantitatively and qualitatively.

Medical applications challenge today's text categorization techniques by demanding both high accuracy and ease-of-interpretation. Although deep learning has provided a leap forward in regard to accuracy, this leap comes at the sacrifice of interpretability. In this paper, we introduce a text categorization approach that leverages the recently introduced Tsetlin Machine to address this accuracy-interpretability challenge. Briefly, we represent the terms of a text as propositional variables. From these variables, we capture categories using simple propositional formulae, such as: IF “rash” AND “reaction” AND “penicillin” THEN Allergy. The Tsetlin Machine learns these formulae from labeled text, utilizing conjunctive clauses to represent the particular facets of each category. Therefore, also the absence of terms (negated features) can be used for categorization purposes. Our empirical comparisons with Naïve Bayes classifiers, decision trees, linear support vector machines (SVMs), random forest, long short-term memory (LSTM) neural networks, and other techniques, are quite conclusive. Using relatively simple propositional formulae, the accuracy of the Tsetlin Machine either outperforms or performs approximately on par with the best evaluated methods on both the 20 Newsgroups and IMDb datasets, as well as on a clinical dataset containing authentic electronic health records (EHRs). On average, the Tsetlin Machine delivers the best recall and precision scores across the datasets. The main merit of the proposed approach is thus its capacity for producing human-interpretable rules, while at the same time achieving acceptable accuracy. We believe that our novel approach can have a significant impact on a wide range of text analysis applications, providing a promising starting point for deeper natural language understanding with the Tsetlin Machine.

Urban green spaces (UGSs) are indispensable for providing various ecosystem services (ESs) to society and city-dwellers. The equitable allocation of ESs provided by UGSs is a prerequisite for maintaining urban sustainability and human well-being. However, empirical studies have assessed the dynamics of UGS equity from ES facets, while neglecting to strengthen integrated evaluation indicators and coupled spatially explicit models. A framework was developed in this study to assess the spatio-temporal patterns of ESs provided by UGSs and their equity based on models of the Intelligent Urban Ecosystem Management System, location entropy, and the Gini coefficient. The results indicated that with urban spatial expansion, in each concentric circle, the values of three ES averages were generally the lowest in the megacity (Xi’an), and the values of carbon sequestration and the recreation averages in the medium-sized cities (Baoji and Xianyang) were also lower than in the small-sized city (Tongchuan). The inequity of ESs provided by UGSs was exacerbated from 2000 to 2020 in the Xi’an Metropolitan Area. The ES equity was the worst in Xi’an and the best in Tongchuan. Areas with extremely low CR location entropy occupied 67.01% in 2020. As cities spatially expanded, areas with extremely low ES location entropy generally increased in 2020. Additionally, the zero-value area of the ES Gini coefficient in Xi’an was the largest from 2000 to 2020. The ES Gini values mostly increased in the same concentric circle of each city in 2020, which demonstrates that equity declined. Spatial equity could be improved by diversifying UGS structures, promoting spatial matching between the ES supply and beneficiaries’ demands, and integrating UGSs into any available space in future UGS planning. The findings of the study could offer insights for optimizing the equitable provision of UGS resources and the targeted planning of urban greening.

Ischemia-reperfusion (I/R) injury is a major side effect of the reperfusion treatment of the ischemic heart. Few therapies are available for the effective prevention of this injury caused by the oxidative stress-induced cardiomyocyte apoptosis. Metformin was shown to have a potential cardiac protective effect and ability to reduce cardiac events, but the exact mechanism remains unclear. Here, we aimed to confirm and investigate the mechanisms underlying potential metformin activity against I/R injury in response to oxidative stress. We determined that the expression of miR-1a-3p was significantly increased in neonatal rat ventricular cells (NRVCs), which were exposed to H2O2 in vitro and in the hearts of mice that underwent the I/R injury. MiR-1a-3p was shown to target the 3′ UTR of GRP94, which results in the accumulation of un- or misfolded proteins, leading to the endoplasmic reticulum (ER) stress. The obtained results demonstrated that C/EBP β directly induces the upregulation of miR-1a-3p by binding to its promoter. Furthermore, as a direct allosteric AMPK activator, metformin was shown to activate AMPK and significantly reduce C/EBP β and miR-1a-3p levels compared with those in the control group. In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP β/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury. Keywords: microRNA, ischemia-reperfusion injury, endoplasmic reticulum stress

Background: Atopic dermatitis (AD) is a common cutaneous disease, associated with imbalances in the skin microbiota.Objective: To explore the characteristics of the cutaneous microbiota and its dynamic changes during clinical treatment.Methods: Cutaneous swab samples were collected from 51 AD patients before treatment, and 40 AD patients remained after a 2-week treatment with mometasone and mupirocin.Results: AD patients exhibited significant enrichments of Prevotella and Desulfovibrio as well as obvious reductions of Corynebacterium, Streptococcus and Parabacteroides. Based on the proportion of Staphylococcus aureus, the AD patients were further classified into S. aureus-predominant group (AD.S) and S. aureus-non-dominant (AD.ND) group. The AD.S group exhibited lower skin microbial diversity and higher atopic dermatitis (SCORAD) index. In the AD.S group, the cutaneous microbial diversity significantly increased from 2.9 ± 0.8 to 3.7 ± 1.0, while the relative abundance of S. aureus decreased from 42.5 ± 20.7 to 10.3 ± 28.4 after treatment. In contrast, no significant skin microbiota changes were detected in the AD.ND group.Conclusions: AD patients with predominant S. aureus had higher disease severity and lower microbiota diversity compared to patients in the AD.ND group. Mometasone and mupirocin therapy had significant effects on skin microbiota in AD.S patients, but had a paradoxical response in the AD.ND patients.

Carbon materials have been widely used as nanozymes in bioapplications, attributing to their intrinsic enzyme-like activities. Nitrogen (N)-doping has been explored as a promising way to improve the activity of carbon material-based nanozymes (CMNs). However, hindered by the intricate N dopants, the real active site of N-doped CMNs (N-CMNs) has been rarely investigated, which subsequently retards the further progress of high-performance N-CMNs. Here, a series of porous N-CMNs with well-controlled N dopants were synthesized, of which the intrinsic peroxidase (POD)like activity has a positive correlation with the pyridinic N content. Density functional theory calculations also reveal that pyridinic N boosts the intrinsic POD-like activity of N-CMNs. Pyridinic-N dopant can effectively promote the first H2O desorption process in comparison with the graphitic and pyrrolic N, which is the key endothermic reaction during the catalytic process. Then, utilizing the optimized nanozymes with high pyridinic N content (NP-CMNs) and superior POD-like activity, a facile total antioxidant capacity (TAC) assay was developed, holding great promise in the quality assessment of medicine tablets and antioxidant food for healthcare and healthy diet.

Tim-3 is a promising target for antitumor immunotherapy. A number of clinical trials are evaluating the efficacy of anti-Tim-3 therapies as a single agent or combinations in solid tumors and haematologic malignancies. However, there remains a considerable lack of data on Tim-3 signalling, especially the genetic characteristics and immune microenvironment, in diffuse large B cell lymphoma (DLBCL). Herein, we identified three genetic mutations in galectin-9, a major ligand of Tim-3, in six patients with DLBCL (6/188, 3.2%) that were not detected in the COSMIC database. The Oncomine database showed that the mRNA levels of Tim-3 were higher in DLBCL cells than those in normal B cells. Multiplexed immunofluorescence revealed that patients with Tim-3-expressing tumor-infiltrating lymphocytes (Tim-3+ TILs) exhibited poor outcomes than those with Tim-3- TILs (p=0.041). The median survival times of these patients were 65.0 (95% confidence interval (CI): 71.2–88.6) and 79.9 months (95% CI: 54.4–75.6), respectively. Furthermore, we defined a novel subtype of exhausted T cells, named as exhausted Tim-3+ CD8+ T cells, and found that patients with exhausted Tim-3+ CD8+ T cells (median survival, 62.8 months, 95% CI: 50.0–75.6) exhibited shorter survival than those with nonexhausted Tim-3- CD8+ T cells (median survival, 82.5 months, 95% CI: 72.0–92.9; p=0.034). Overall, these findings provide the genetic status of the Tim-3 ligand in DLBCL. Patients with Tim-3+ TILs and exhausted Tim-3+ CD8+ T cells exhibited inferior survival, thus highlighting the possibility of potential therapeutic applications of the inhibition of Tim-3 alone or in combination with other immune checkpoints for treatment of patients with DLBCL.

The ZrB _2 /A356 composite material was prepared by using chemical in situ reaction technology. The high-temperature friction and wear test of ZrB _2 /A356 aluminum matrix composites was carried out. The friction and wear test temperatures were normal temperatures, 50 °C, 100 °C, 150 °C, 200 °C, 250 °C, and 300 °C. XRD, TEM, SEM, and XPS were used to analyze the microstructure, phase and the formation of surface compounds of the composites under different wear temperatures. The results show that the composite phase is composed of ZrB _2 and ɑ-Al, and there is a small amount of Al-Si eutectic phase; ZrB _2 particles are small, hexagonal nearly elliptical, flocculent and well bonded to the matrix; Combined with the stress-strain curve and tensile fracture morphology analysis, the composite material is a ductile fracture, and the plasticity of the A356 alloy is higher than that of the composite material; The wear properties of composites are susceptible to temperature changes, and the wear rate is small below 200 °C. The wear mechanism is mainly oxidative wear and abrasive wear. When the temperature reaches above 250 °C, the wear rate begins to rise sharply, and a large number of plastic deformation traces and wear debris appear on the surface of the wear spot, and the surface of the wear debris adheres to the protrusions. The primary wear mechanism is adhesive wear. In the stages of oxidative wear, and abrasive wear, although the friction coefficient changes, it is stable. But in the adhesive wear stage, the friction coefficient becomes very unstable and a sharp peak appears. XPS analysis showed that the compounds formed in the wear scar were mainly Al _2 O _3 .

Background: To evaluate the one-year immunogenicity and safety of a subunit plague vaccine. Methods: In the initial study, 240 healthy adults aged 18–55 years were administrated with 2 doses of 15 or 30 µg plague vaccines at day 0 and 28, respectively. In this extended follow-up study, we evaluated the immunogenicity and safety of the plague vaccine up to one year. Results: For antibody to envelope antigen faction 1 (F1) antigen, titers were up to new peaks at month 6, then declined slowly to month 12, but remained at higher levels than those at day 56. Geometric mean titers (GMTs) of F1 were significantly higher in 30 µg group than those in 15 µg group at month 6 and 12 (P < 0.0001 and P < 0.001). However, approximate 100% seroconversion rates of F1 antibodies were found in both 15 and 30 µg groups at the both time points. For antibody to recombinant virulence (rV) antigen, titers and seroconversion rates were decreased sharply at month 6 and continue to decrease at month 12. GMTs and seroconversion rates were not significantly different between the 15 and 30 µg groups, respectively. No serious adverse events (SAEs) related to vaccine occurred. Conclusion: The new plague vaccine (F1+rV) induced a robust immune response up to 12 months and showed a good safety profile in adults aged 18–55 years.

Long noncoding RNAs have been shown to play a role in cardiovascular disease. Here, the authors identify a lncRNA named CCRR, whose downregulation in failing hearts causes cardiac conduction disturbances by altering the endocytic trafficking of Cx43.

Abstract Background Previous studies have documented that visceral adipose tissue is positively associated with the risk of diabetes. However, the association of subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to assess the associations between different adipose distributions and the risk of newly diagnosed diabetes in Chinese adults. Methods The Shanghai Nicheng Cohort Study was conducted among Chinese adults aged 45–70 years. The baseline data of 12,137 participants were analyzed. Subcutaneous and visceral fat area (SFA and VFA) were measured by magnetic resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose tolerance test. Results The multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of newly diagnosed diabetes per 1—standard deviation increase in SFA and VFA were 1.29 (1.19–1.39) and 1.61 (1.49–1.74) in men, and 1.10 (1.03–1.18) and 1.56 (1.45–1.67) in women, respectively. However, the association between SFA and newly diagnosed diabetes disappeared in men and was reversed in women (OR 0.86 [95% CI, 0.78–0.94]) after additional adjustment for body mass index (BMI) and VFA. The positive association between VFA and newly diagnosed diabetes remained significant in both sexes after further adjustment for BMI and SFA. Areas under the receiver operating characteristic curve of newly diagnosed diabetes predicted by VFA (0.679 [95% CI, 0.659–0.699] for men and 0.707 [95% CI, 0.690–0.723] for women) were significantly larger than by the other adiposity indicators. Conclusions SFA was beneficial for lower risk of newly diagnosed diabetes in women but was not associated with newly diagnosed diabetes in men after taking general obesity and visceral obesity into account. VFA, however, was associated with likelihood of newly diagnosed diabetes in both Chinese men and women.

Background/Aims: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms. Methods: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model. To investigate the role of Cav3 in cardiac fibrosis, we transfected cardiac fibroblasts (CFs) with the siRNA of Cav3 and Cav3-overexpressing plasmid. The collagen content and proliferation of CFs were detected by qRT-PCR, western blot, MTT, and immunofluorescence. A luciferase reporter gene assay and gain/loss of function were used to detect the relationship between miR-22 and Cav3. Results: Cav3 depletion in CFs induced an increase in collagen content, cell proliferation, and phenotypic conversion of fibroblasts to myofibroblasts. Conversely, Cav3 overexpression in CFs was shown to inhibit angiotensin II-mediated excessive collagen deposition through protein kinase C (PKC)ε inactivation. Cav3 was experimentally confirmed as a direct target of miR-22, containing two seed binding sites in its 3′-untranslated region, and miR-22 was demonstrated to be significantly upregulated in the ischemic border zone in mice after myocardial infarction and in neonatal rat CFs pretreated with angiotensin II. miR-22 overexpression increased CFs proliferation, and collagen and α-smooth muscle actin levels in CFs, while the knockdown of endogenous miR-22 decreased CFs numbers. Conclusions: Our findings demonstrate that miR-22 accelerates cardiac fibrosis through the miR-22-Cav3-PKCε pathway, which, therefore, may represent a new therapeutic target for treatment of excessive fibrosis-associated cardiac diseases.