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Abstract Global measurements of ocean p C O 2 are critical to monitor and understand changes in the global carbon cycle. However, p C O 2 observations remain sparse as they are mostly collected on opportunistic ship tracks. Several approaches, especially based on direct learning, have been used to upscale and extrapolate sparse point data to dense estimates using globally available input features. However, these estimates tend to exhibit spatially heterogeneous performance. As a result, we propose a physics-informed transfer learning workflow to generate dense p C O 2 estimates that are grounded in real-world measurements and remain physically consistent. The models are initially trained on dense input predictors against p C O 2 estimates from Earth system model simulation, and then fine-tuned to sparse SOCAT observational data. Compared to the benchmark direct learning approach, our transfer learning framework shows major improvements of up to 56-92%. Furthermore, we demonstrate that using models that explicitly account for spatiotemporal structures in the data yield better validation performances by 50-68%. Our strategy thus presents a new monthly global p C O 2 estimate that spans for 35 years between 1982-2017.

Abstract As the severity of global climate change escalates, carbon peak and carbon neutrality have emerged as international imperatives. Green taxation, a crucial fiscal strategy promoting the transition to a green low-carbon economy, demands thorough investigation regarding its efficacy and operational mechanisms. Predominantly, existing research has concentrated on the macroeconomic implications of green taxes, while their influence on regional green growth and innovation remains underexplored. This paper delineates green taxation in both a broad and narrow sense, elucidating its essence and potential in stimulating regional green progress and innovation. Utilizing panel data from 30 provinces in China spanning 2004 to 2021, a bidirectional fixed-effects model was developed for empirical analysis. Moreover, an impact mechanism model was constructed to delve into how green taxation specifically affects regional green development and innovation. Findings reveal that green taxation significantly fosters regional green growth and markedly enhances green innovation. Nonetheless, due to the resource crowding-out effect, it adversely impacts the comprehensive innovation capabilities of regional enterprises. This insight offers a fresh perspective on the paradoxical effects of green taxation, underscoring the necessity for a balanced approach in policy design and implementation. Drawing on these conclusions, the paper presents tailored policy recommendations.

Abstract The parameterization of suspended sediments in vegetated flows presents a significant challenge, yet it is crucial across various environmental and geophysical disciplines. This study focuses on modeling suspended sediment concentrations (SSC) in vegetated flows with a canopy density of avH ∈ [0.3, 1.0] by examining turbulent dispersive flux. While conventional studies disregard dispersive momentum flux for avH > 0.1, our findings reveal significant dispersive sediment flux for large particles with a diameter‐to‐Kolmogorov length ratio when dp/η > 0.1. Traditional Rouse alike approaches therefore must be revised to account for this effect. We introduce a hybrid methodology that combines physical modeling with machine learning to parameterize dispersive flux, guided by constraints from diffusive and settling fluxes, characterized using recent covariance and turbulent settling methods, respectively. The model predictions align well with reported SSC data, demonstrating the versatility of the model in parameterizing sediment‐vegetation interactions in turbulent flows.

Abstract To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593–0.9996) in the training cohort and 0.909 (95% CI 0.7921–1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

Abstract Objective ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. Research design and methods Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. Results Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. Conclusions PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

To provide a scoping review of studies on factors affecting smoking cessation in patients with chronic obstructive pulmonary disease (COPD), so as to provide a basis for healthcare professionals to intervene early in the process of cessation of smoking in patients with COPD, and to formulate personalized interventions for smoking cessation. Arksey and O’Malley’s scoping review methodology as a framework, searched databases including CNKI, Wanfang Data, VIP, China Biomedical Database, PubMed, Web of Science, Embase, ProQuest, CINAHL, and Cochrane Library to collect literature on factors influencing smoking cessation among COPD patients. The literature was screened, data extracted, and summarized accordingly. A total of 28 papers were included. The socio-demographic related factors affecting smoking cessation in patients with COPD were age, educational level, residence, marital status, occupational status, economic status, race, and sex; tobacco related factors included smoking index, smoking duration (years), cumulative smoking (packs/year), smoking intensity (packs/day), and tobacco addiction; disease related factors included mMRC score, GOLD level, severity of airflow restrictions, symptom, activity limitation due to lung problems, history of deterioration in outpatient care, receipt of COPD medication, receipt of lung CT, receipt of pulmonary function tests, receipt of surgery, and comorbid comorbidities; psychologically related factors included mental health status, quit smoking health beliefs, smoking cessation self-efficacy, motivation to quit smoking, stress, and adverse emotions; environmental/Interpersonal network related factors-included environmental impacts, social support, family support, tobacco control policies, and satisfaction with cessation care; and behavior related factors included alcohol consumption, coffee consumption, eating, physical activity, and have a hobby. Healthcare professionals should avoid critical education of COPD patients in the process of smoking cessation management, pay attention to the adverse effects of medication side effects on patients, emphasize the improvement of patients’ health beliefs and self-efficacy in smoking cessation, and help patients to establish a correct cognition of smoking cessation.

Skeletal diseases impose a considerable burden on society. The clinical and tissue-engineering therapies applied to alleviate such diseases frequently result in complications and are inadequately effective. Research has shifted from conventional therapies based on mesenchymal stem cells (MSCs) to exosomes derived from MSCs. Exosomes are natural nanocarriers of endogenous DNA, RNA, proteins, and lipids and have a low immune clearance rate and good barrier penetration and allow targeted delivery of therapeutics. MSC-derived exosomes (MSC-exosomes) have the characteristics of both MSCs and exosomes, and so they can have both immunosuppressive and tissue-regenerative effects. Despite advances in our knowledge of MSC-exosomes, their regulatory mechanisms and functionalities are unclear. Here we review the therapeutic potential of MSC-exosomes for skeletal diseases.

Rice cake is a common traditional food in China. In this study, the effect of Polygonatum cyrtonema (PC) on the qualities and characteristics of rice cake was investigated. The incorporation of PC powder in rice cakes endowed a light-yellow color and increased the water content and water absorption of products. Rheological analysis showed that the rice cake containing PC exhibited weak-gel properties. Additionally, PC (40%) inhibited the rice cake aging and lowered the hardness of rice cakes to 13.86 N after 4 h storage. In vitro starch digestion analysis showed that PC (40%) reduced the digestibility of rice cakes by decreasing the starch hydrolysis rate from 88.70 to 58.95%, displaying a low estimated glycemic index (eGI) of 52.14. The findings mentioned above indicated that the inclusion of PC powder in rice cakes enhanced their characteristics and attributes, which also provided an approach for the development of PC products.

Objective To observe the effect of Traditional Chinese Medicine nursing technique combined with humanistic nursing intervention in the treatment of elderly patients with insomnia. Methods Totally 80 elderly patients with insomnia were divided into observation group and control group, 40 cases in each group. The control group was given routine nursing, and the observation group was given TCM techniques-auricular acupoint pressing combined with humanistic nursing intervention. The sleep quality was evaluated by Pittsburgh Sleep quality index (PSQI)before and after 2 months of intervention. Results The PSQI score was decreased in both two groups after intervention, and PSQI score in the observation group was lower than that in the control group, with a significant difference(P＜0. 01). Conclusion TCM nursing technique combined with humanistic nursing intervention can effectively improve sleep quality of elderly patients with insomnia (目的 探讨中医特色护理技术联合人文关怀护理干预老年失眠患者的效果观察。方法 选取2019年5月—2020年5月医院收治的80例老年失眠患者为研究对象, 分为观察组与对照组, 各40例。对照组给予常规护理, 观察组在对照组基础上给予中医耳穴贴压联合人文关怀护理。采用匹兹堡睡眠质量指数(PSQI)评估患者干预前及干预2个月后睡眠功能改善情况。结果 干预后, 两组PSQI量表评分均较干预前降低, 且观察组PSQI评分低于观察组, 差异有统计学意义(P＜0. 01)。结论 中医特色护理技术耳穴贴压联合人文关怀护理干预能有效改善老年失眠患者睡眠质量。)

To investigate the parametric rolling motion of container ships navigating in head seas, this study utilizes the unsteady RANS approach combined with dynamic overlapping grid technology to simulate parametric roll in a container ship under the coupled motions of roll, pitch, and heave. Initially, the model was validated against experimental results, demonstrating good agreement and thus confirming the reliability of the computational method. Furthermore, the paper investigates the impacts of the initial roll angle, encounter frequency, and the addition of bilge keels on parametric rolling. The research findings indicate that the initial angles of rolling impact the duration needed to attain a steady roll condition, yet they have minimal effect on the amplitude post-stabilization. The likelihood of parametric rolling arises when the frequency of encounters doubles that of the ship’s inherent roll frequency. Furthermore, the likelihood of parametric rolling escalates when the wavelengths approach the length of the ship. Installing bilge keels markedly reduces the parametric rolling movement in vessels, and the occurrence of parametric rolling is also delayed.

Abstract Flexible strain sensors are capable to detect external force induced strain change owing to their unique ability to convert deformation into electrical signals. Generally, micro/nano patterning of conductive layer in strain sensor is an effective method to improve its sensitivity, however the sophisticated manipulation process is limited only in laboratory scale. In this report, a simple and scalable fabrication strategy was used to create micro-cracking conductive layer as an alternative patterning method to achieve high performance of strain sensor. In details, the sensor was fabricated using leather as the substrate to filtrated acidified multi-walled carbon nanotubes (a-MWCNTs)/layered double hydroxides (LDHs) suspension. During stretching process, micro-cracking structure emerged on the percolated a-MWCNTs/LDHs layer, causing a rise up of resistance according to increasing strain and generated a detectable electrical signal. The prepared sensor had a large detecting range (60%), high sensitivity (GF of 7238.92 at strain 30–60%), fast response (tensile response time of 270 ms), good stability and repeatability. The sensor also inherited the advantages of leather, such as biodegradability and good air permeability, and the introduction of a-MWCNTs/LDHs further enhanced its fire retardancy properties. These features ensured the sensor as an eco-friendly, comfortable and safe electronic device for human motion detection. Graphical abstract

Sensing and understanding large-scale dynamic scenes require a high-performance imaging system. Conventional imaging systems pursue higher capability by simply increasing the pixel resolution via stitching cameras at the expense of a bulky system. Moreover, they strictly follow the feedforward pathway: That is, their pixel-level sensing is independent of semantic understanding. Differently, a human visual system owns superiority with both feedforward and feedback pathways: The feedforward pathway extracts object representation (referred to as memory engram) from visual inputs, while, in the feedback pathway, the associated engram is reactivated to generate hypotheses about an object. Inspired by this, we propose a dual-pathway imaging mechanism, called engram-driven videography. We start by abstracting the holistic representation of the scene, which is associated bidirectionally with local details, driven by an instance-level engram. Technically, the entire system works by alternating between the excitation–inhibition and association states. In the former state, pixel-level details become dynamically consolidated or inhibited to strengthen the instance-level engram. In the association state, the spatially and temporally consistent content becomes synthesized driven by its engram for outstanding videography quality of future scenes. The association state serves as the imaging of future scenes by synthesizing spatially and temporally consistent content driven by its engram. Results of extensive simulations and experiments demonstrate that the proposed system revolutionizes the conventional videography paradigm and shows great potential for videography of large-scale scenes with multi-objects.

Abstract Projected increases in hurricane intensity under a warming climate will have profound effects on many forest ecosystems. One key challenge is to disentangle the effects of wind damage from the myriad factors that influence forest structure and species distributions over large spatial scales. Here, we employ a novel machine learning framework with high‐resolution aerial photos, and LiDAR collected over 115 km2 of El Yunque National Forest in Puerto Rico to examine the effects of topographic exposure to two hurricanes, Hugo (1989) and Georges (1998), and several landscape‐scale environmental factors on the current forest height and abundance of a dominant, wind‐resistant species, the palm Prestoea acuminata var. montana. Model predictions show that the average density of the palm was 32% greater while the canopy height was 20% shorter in forests exposed to the two storms relative to unexposed areas. Our results demonstrate that hurricanes have lasting effects on forest canopy height and composition, suggesting the expected increase in hurricane severity with a warming climate will alter coastal forests in the North Atlantic.

BackgroundPostpartum depression (PPD) is considered the most widespread puerperium complication. The associations of major depressive disorder with certain types of cerebrovascular diseases and cognitive function have been proposed, but the potential causal effects of PPD on these phenotypes are still unknown.MethodsA Mendelian randomization (MR) research design with various methods (e.g., inverse-variance weighted method and MR pleiotropy residual sum and outlier test) was adopted to establish a causal relationship between PPD with cerebrovascular diseases and cognitive impairment.ResultsNo causal relationship between PPD with carotid intima media thickness and cerebrovascular diseases (i.e., stroke, ischemic stroke, and cerebral aneurysm) was found. However, MR analyses indicated a causal association between PPD and decreased cognitive function (P = 3.55 × 10−3), which remained significant even after multiple comparison corrections using the Bonferroni method. Sensitivity analyses using weighted median and MR-Egger methods indicated a consistent direction of the association.ConclusionThe causal association between PPD and cognitive impairment indicates that cognitive impairment is a critical aspect of PPD and thus cannot be regarded as an epiphenomenon. Addressing cognitive impairment and lessening the symptoms associated with PPD independently play significant roles in the treatment of PPD.

To summarize the nursing experience of an elderly patient with chronic constipation of Qi-blood deficiency syndrome treated by auricular acupoint sticking and pressing therapy. On the basis of routine nursing such as dietary nursing, psychological adjustment and health education, the auricular acupoint sticking therapy was performed. According to the characteristics of disease and the patient, targeted nursing measures were carried out to relieve the constipation and related clinical symptoms. (总结耳穴贴压治疗1例老年慢性气血两虚型便秘患者的护理经验。在完善饮食护理、心理调适、健康指导等常规护理的基础上, 给予耳穴贴压治疗, 并根据疾病和患者特点, 采用相应的护理措施, 积极改善患者便秘症状。)

Abstract The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

Mutation detecting is a routine work for sequencing data analysis and the trading of existing tools often involves the combinations of signals on a set of overlapped sequencing reads. However, the subclonal mutations, which are reported to contribute to tumor recurrence and metastasis, are sometimes eliminated by existing signals. When the clonal proportion decreases, signals often present ambiguous, while complicated interactions among signals break the IID assumption for most of the machine learning models. Although the mutation callers could lower the thresholds, false positives are significantly introduced. The main aim here was to detect the subclonal mutations with high specificity from the scenario of ambiguous sample purities or clonal proportions. We proposed a novel machine learning approach for filtering false positive calls to accurately detect mutations with wide spectrum subclonal proportion. We have carried out a series of experiments on both simulated and real datasets, and compared to several state-of-art approaches, including freebayes, MuTect2, Sentieon and SiNVICT. The results demonstrated that the proposed method adapts well to different diluted sequencing signals and can significantly reduce the false positive when detecting subclonal mutations. The codes have been uploaded at https://github.com/TrinaZ/TL-fpFilter for academic usage only.

Detecting SNV at very low read depths helps to reduce sequencing requirements, lowers sequencing costs, and aids in the early screening, diagnosis, and treatment of cancer. However, the accuracy of SNV detection is significantly reduced at read depths below ×34 due to the lack of a sufficient number of read pairs to help filter out false positives. Many recent studies have revealed the potential of mutational signature (MS) in detecting true SNV, understanding the mutational processes that lead to the development of human cancers, and analyzing the endogenous and exogenous causes. Here, we present DETexT, an SNV detection method better suited to low read depths, which classifies false positive variants by combining MS with deep learning algorithms to mine correlation information around bases in individual reads without relying on the support of duplicate read pairs. We have validated the effectiveness of DETexT on simulated and real datasets and conducted comparative experiments. The source code has been uploaded to https://github.com/TrinaZ/extra-lowRD for academic use only.

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW.Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome.Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10–3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis.Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.

Summary: High-dimensional mass cytometry provides unparalleled insight into the cellular composition of the immune system. Here, we describe a mass-cytometry-based protocol to examine memory CD4+ T cell and memory B cell (MBC) responses in human peripheral blood. This approach allows for the identification of >50 distinct memory CD4+ T cell and MBC populations from a single clinical sample. This highly reproducible protocol has been successfully applied to multiple infectious disease settings to identify correlates of susceptibility or protection from infection.For complete details on the use and execution of this protocol, please refer to Ioannidis et al. (2021).

Abstract Background Genotyping of structural variation is an important computational problem in next generation sequence data analysis. However, in cancer genomes, the copy number variant(CNV) often coexists with other types of structural variations which significantly reduces the accuracy of the existing genotype methods. The bias on sequencing coverage and variant allelic frequency can be observed on a CNV region, which leads to the genotyping approaches that misinterpret the heterozygote as a homozygote. Furthermore, other data signals such as split mapped read, abnormal read will also be misjudged because of the CNV. Therefore, genotyping the structural variations with CNV is a complicated computational problem which should consider multiple features and their interactions. Methods Here we proposed a computational method for genotyping indels in the CNV region, which introduced a machine learning framework to comprehensively incorporate a set of data features and their interactions. We extracted fifteen kinds of classification features as input and different from the traditional genotyping problem, here the structure of variant may fall into types of normal homozygote, homozygous variant, heterozygous variant without CNV, heterozygous variant with a CNV on the mutated haplotype, and heterozygous variant with a CNV on the wild haplotype. The Multiclass Relevance Vector Machine (M-RVM) was used as a machine learning framework combined with the distribution characteristics of the features. Results We applied the proposed method to both simulated and real data, and compared it with the existing popular softwares include Gindel, Facets, GATK, and also compared with other machine learning cores: Support Vector Machine, Lanrange-SVM with OVO multiple classification, Naïve Bayes and BP Neural Network. The results demonstrated that the proposed method outperforms others on accuracy, stability and efficiency. Conclusion This work shows that the genotyping of structural variations on the CNV region cannot be solved as a traditional genotyping problem. More features should be used to efficiently complete the five-category task. According to the result, the proposed method can be a practical algorithm to correct genotype structural variations with CNV on the next generation sequence data. The source codes have been uploaded at https://github.com/TrinaZ/Mixgenotype for academic usage only.

Objective. Repair of cartilage defects, a common condition resulting from many factors, is still a great challenge. Based on their chondrogenic differentiation ability, mesenchymal stem cell- (MSC-) based cartilage regeneration is a promising approach for cartilage defect repair. However, MSC differentiation into chondroblasts or related cell lineages is elaborately controlled by stem cell differentiation stage factors and affected by an array of bioactive elements, which may impede the efficient production of target cells. Thus, identifying a single transcription factor to promote chondrogenic differentiation is critical. Herein, we explored the mechanism by which scrapie-responsive gene 1 (SCRG1), a candidate gene for cartilage regeneration promotion, regulates chondrogenic differentiation of MSCs. Methods. Expression of SCRG1 was detected in umbilical cord-derived MSCs (UCMSCs) by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis during chondrogenic differentiation. The function of SCRG1 in chondrogenic potential was evaluated after gene knockdown or overexpression by lentiviral vectors. Finally, a rabbit cartilage defect model was established to evaluate the effect of SCRG1 on cartilage repair in vivo. Results. Expression of SCRG1 was upregulated during in vitro chondrogenic differentiation of UCMSCs. SCRG1 knockdown inhibited chondrogenic differentiation of UCMSCs, while SCRG1 overexpression promoted chondrogenic differentiation of UCMSCs in vitro. In addition, UCMSC overexpressing SCRG1 promoted cartilage repair in vivo. Mechanistically, SCRG1 promoted chondrogenic differentiation via upregulation of Wnt5a expression and subsequent inhibition of β-catenin. Conclusion. Our results showed that SCRG1 promotes chondrogenic differentiation of UCMSCs by inhibiting canonical Wnt/β-catenin signaling through Wnt5a. Our findings provide a future target for chondrogenic differentiation and cartilage regeneration.

Texture analysis (TA) is a newly arisen field that can detect the invisible MRI signal changes among image pixels. Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, becoming the primary cause of death and disability worldwide. In recent years, various TA studies have been performed in patients with MI and show a good clinical application prospect. This review briefly presents the main pathogenesis and pathophysiology of MI, introduces the overview and workflow of TA, and summarizes multiple magnetic resonance TA (MRTA) clinical applications in MI. We also discuss the facing challenges currently for clinical utilization and propose the prospect.

AIM: To compare the safety and efficacy of subconjunctival injection with conbercept and 5-fluorouracil (5-FU) for open angle glaucoma (OAG) patients after filtration surgery. METHODS: As a prospective randomized interventional trial, 36 eyes from 36 patients after OAG surgery were collected and divided randomly into conbercept and 5-FU groups. All patients were subconjunctivally injected with either conbercept (0.2 mL) or 5-FU (0.2 mL) on the 5th day post-operatively. The intraocular pressure (IOP), number of medications used, type of conjunctival bleb, and complications were recorded and analyzed pre-operatively and 1d, 1wk, 1, 3 and 6mo post-injection. RESULTS: There were significant differences in IOP between the conbercept and 5-FU groups 1mo (conbercept group: 12.17±1.04 mm Hg; 5-FU group: 13.50±2.33 mm Hg, t=2.214, P=0.037), 3mo (conbercept group: 13.00±1.88 mm Hg; 5-FU group: 14.50±2.28 mm Hg, t=2.153, P=0.039), and 6mo post-injection (conbercept group: 13.28±2.95 mm Hg; 5-FU group: 15.22±2.49 mm Hg, t=2.140, P=0.040); however, in the number of medications, a prominent difference was not shown between groups on post-injection 6mo (t=1.312, P=0.200). Moreover, there was mild vascularity observed in the conbecept group than the 5-FU group 1d (3a, 3b, 3c: t=8.497, 6.693, 4.515, P=0.000), 1wk (3a, 3b, 3c: t=3.431, 6.408, 3.984, P=0.002, 0.000, 0.000), and 1mo post-injection (3a, 3b, 3c: t=2.466, 2.466, 2.503, P=0.019, 0.019, 0.017). Simultaneously, differences from other indicators between the two groups were not demonstrated. Also, there was a lower probability of corneal epithelial stripping in the conbercept group than the 5-FU group (χ2=4.500, P=0.034). CONCLUSION: Subconjunctival injection of conbercept has a safe, effective, and tolerable profile for open angle glaucoma patients with distinct conjunctival congestion after filtration surgery.

Purpose. The purpose of this study was to assess the efficacy and safety of intraocular direct cyclophotocoagulation (IDCP) using a 532 nm laser with combination treatment in reducing intraocular pressure (IOP) for patients with advanced neovascular glaucoma (NVG) with angle closure. In addition, we sought to determine the success rate and frequency of complications and explore an optimized solution to reduce the number of topical medications and the pain of patients. Methods. A retrospective case note review of all patients undergoing combined treatment including IVR, phaco, PPV, PRP, and IDCP from January 2017 to June 2018. Results. In total, 24 consecutive patients (25 eyes) were reviewed. The mean IOP was significantly decreased from 42.2 ± 8.5 mmHg preoperatively to 15.56 ± 2.0 mmHg (P

Glucocorticoid-induced glaucoma (GIG) is a chronic optic neuropathy caused by systemic or topical glucocorticoid (GC) treatment, which could eventually lead to permanent vision loss. To investigate the protective effects of rapamycin (RAP) on the trabecular cells during the development of GIG in mice, the effects of RAP on intraocular pressure (IOP), trabecular ultrastructure, and retinal ganglion cells (RGCs) were examined in C57BL/6J female mice treated with dexamethasone acetate (Dex-Ace). The expression of α-actin in trabecular tissue was detected by immunofluorescence, and the autophagic activity of trabecular cells and the expression of GIG-related myocilin and α-actin were detected by immunoblotting. Our results indicated that Dex-Ace significantly increased IOP at the end of the third week (p < 0.05), while RAP treatment neutralized this elevation of IOP by Dex-Ace. Dex-Ace treatment significantly decreased the RGC numbers (p < 0.05), while synchronous RAP treatment kept the number comparable to control. The outer sheath of elastic fibers became thicker and denser, and the mitochondria of lesions increased in Dex-Ace-treated groups at 4 weeks, while no significant change was observed in the RAP-treated trabecular tissues. Dex-Ace induced myocilin, α-actin, Beclin-1, and LC3-II/LC-I ratio, and lowered p62, while synchronous RAP treatment further activated autophagy and neutralized the induction of myocilin and α-actin. Our studies suggested that RAP protected trabecular meshwork cells by further inducing autophagy way from damages of GC treatment.

Abstract In this paper, a fully statistical investigation of the control of family structure as random effects is analyzed and discussed, using both the genome-wide association studies (GWAS) data and simulated data. Three modeling strategies are proposed and the analysis results suggest the hybrid use of results from all possible models should be combined in practice.

In this study, two new metal-organic frameworks, namely, {(H2NMe2)[Zn3LiO(BTA)2](DMF)3}n (1, H3BTA=3,3′,3″-[1,3,5-benzenetriyltris(carbonylimino)] trisbenzoic acid) and {(Me2NH2)2[In2(TTA)2(FBA)2](DMF)3}n (2, H3TTA=4,4′-(((5-((4-(hydroxy-l2-methoxy)phenoxy) methyl)-2,4,6-trimethyl-1,3-phenylene)bis(methylene))bis(oxy))dibenzoic acid, HFBA=2-fluorobenzoic acid), were obtained via a one-pot solvothermal reaction of metal salts and organic connectors. The structures of the title two metal-organic coordination compounds were structurally probed via X-ray single crystal diffraction technique. In connection to their structures, the MTT assay was used to access the in vitro antitumor activities for compounds 1 and 2 against the human lung cancer cells (MSTO-211H, NCI-H1299 and NCI-H292).

Existing methods to estimate the prevalence of chronic hepatitis C (HCV) in New York City (NYC) are limited in scope and fail to assess hard-to-reach subpopulations with highest risk such as injecting drug users (IDUs). To address these limitations, we employ a Bayesian multi-parameter evidence synthesis model to systematically combine multiple sources of data, account for bias in certain data sources, and provide unbiased HCV prevalence estimates with associated uncertainty. Our approach improves on previous estimates by explicitly accounting for injecting drug use and including data from high-risk subpopulations such as the incarcerated, and is more inclusive, utilizing ten NYC data sources. In addition, we derive two new equations to allow age at first injecting drug use data for former and current IDUs to be incorporated into the Bayesian evidence synthesis, a first for this type of model. Our estimated overall HCV prevalence as of 2012 among NYC adults aged 20–59 years is 2.78% (95% CI 2.61–2.94%), which represents between 124,900 and 140,000 chronic HCV cases. These estimates suggest that HCV prevalence in NYC is higher than previously indicated from household surveys (2.2%) and the surveillance system (2.37%), and that HCV transmission is increasing among young injecting adults in NYC. An ancillary benefit from our results is an estimate of current IDUs aged 20–59 in NYC: 0.58% or 27,600 individuals. Keywords: Bayesian evidence synthesis, Disease prevalence estimation, Hard-to-reach populations, Injecting drug use, hepatitis C in New York City

Magnetoelectric materials by converting a magnetic input to a voltage output holds promise in contactless electrodes that find applications from energy harvesting to sensing. Zong et al. report a promising laminate composite that combines a piezoelectric biopolymer, cellulose, and a magnetic material.

Background. Endoplasmic reticulum stress (ERS) in the retinal Müller cells is a key factor contributing to the retinal inflammation and vascular leakage in diabetic retinopathy (DR). This study was to investigate the underlying mechanisms through which the 3 main unfolded protein response (UPR) pathways regulate ERS and to examine the expression levels of vascular endothelial growth factor (VEGF) in Müller cells in vitro. Methods. Rat Müller cell lines were stimulated with high glucose to mimic a diabetic environment in vitro. PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6) were downregulated or upregulated with shRNA or overexpression plasmids. The transfected Müller cells were cultivated in high glucose medium for 48 hours. Expression of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), X-box binding protein 1 (XBP1), ATF6, and VEGF was examined with immunofluorescence and western blot. Results. Our data indicated that ERS was found in both high glucose and osmotic control groups. Overexpression or downregulation of UPR pathways effectively increased or reduced the production of GRP78, ATF4, XBP1, ATF6, and VEGF, respectively. These 3 signaling pathways had similar regulatory effects on VEGF. Conclusion. The 3 UPR-mediated inflammatory pathways were dependent on each other. Inhibition any of these signaling pathways in UPR might be a potential therapeutic target for DR.

Purpose. To investigate the changes of retinal nerve fiber layer (RNFL) in patients after an attack of primary acute angle closure glaucoma (PAACG) and to assess the impact of attack time on prognosis of retinal changes. Design. cross-sectional study. Methods. Twenty-six patients with unilateral PAACG attack and cataracts from 2017 to 2019 were enrolled. Eyes with PAACG attack time less than 1 day constituted the group A (n = 13), while eyes with PAACG attack time more than 1 day constituted the group B (n = 13). All patients received phacoemulsification and viscogoniosynechialysis after intraocular pressure (IOP) lowering. All patients underwent ophthalmic examinations including IOP, best-corrected visual acuity (BCVA), and visual field (VF). Optical coherence tomography angiography (OCTA) was used to obtain circumpapillary RNFL vessel density (cpVD). Spectral domain optical coherence tomography (SD-OCT) was used to examine the peripapillary RNFL and macular ganglion cell complex (GCC). All patients accepted 2 assessments before and 1 month after the procedure. Results. The IOP of all patients recovered to normal (12.77 ± 2.65 mm Hgvs. 12.77 ± 3.85 mmHg, p=0.834) after the procedure. Patients in the group A had better BCVA improvement than those in the group B (1.32 ± 0.84 vs. 0.50 ± 0.21, p=0.004), as well as better mean defect (MD) values from VF (−3.65 ± 2.54 vs −16.05 ± 5.99, p

Open chromatin regions (OCRs) are special regions of the human genome that can be accessed by DNA regulatory elements. Several studies have reported that a series of OCRs are associated with mechanisms involved in human diseases, such as cancers. Identifying OCRs using ATAC-seq or DNase-seq is often expensive. It has become popular to detect OCRs from plasma cell-free DNA (cfDNA) sequencing data, because both the fragmentation modes of cfDNA and the sequencing coverage in OCRs are significantly different from those in other regions. However, it is a challenging computational problem to accurately detect OCRs from plasma cfDNA-seq data, as multiple factors—e.g., sequencing and mapping bias, insufficient read depth, etc.—often mislead the computational model. In this paper, we propose a novel bioinformatics pipeline, OCRDetector, for detecting OCRs from whole-genome cfDNA sequencing data. The pipeline calculates the window protection score (WPS) waveform and the cfDNA sequencing coverage. To validate the proposed pipeline, we compared the percentage overlap of our OCRs with those obtained by other methods. The experimental results show that 81% of the TSS regions of housekeeping genes are detected, and our results have obvious tissue specificity. In addition, the overlap percentage between our OCRs and the high-confidence OCRs obtained by ATAC-seq or DNase-seq is greater than 70%.

Lactobacillus plantarum SKT109 was isolated and identified from Tibet Kefir, and the exopolysaccharride (EPS)-producing properties of the strain were evaluated. Growth of strain SKT109 in a semi-defined medium at 37°C increased the viscosity of the medium, corresponding to production of an EPS (58.66 mg/L). The EPS was isolated and purified, and it was shown to consist of fructose and glucose in an approximate molar ratio of 3:1, with an average molecular weight of 2.1×106 Da. The aqueous solution of EPS at 1% (w/v) exhibited shear thinning behavior. Microstructural studies of the EPS demonstrated a highly compact structure with a smooth surface, facilitating formation of film by the polymer; the EPS was composed of many different sizes of spherical lumps with tendency to form molecular aggregates. Studies on the milk fermentation characteristics of L. plantarum SKT109 showed that the strain survived well in fermented milk with counts about 8.0 log cfu/g during 21 days of storage at 4°C. The use of the EPS-producing strain improved the rheology of the fermented milk without causing post-acidification during storage. Particularly, L. plantarum SKT109 improved the fermented milk flavor by increasing the concentration of characteristic flavor compounds and eliminating those with dis gusting flavors. The results of the present study indicated that EPS-producing L. plantarum SKT109 could serve as a promising candidate for further exploitation in fermented foods.