Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Inner Surface Design of Functional Microchannels for Microscale Flow Control.

Fluidic flow behaviors in microfluidics are dominated by the interfaces created between the fluids and the inner surface walls of microchannels. Microchannel inner surface designs, including the surface chemical modification, and the construction of micro-/nanostructures, are good examples of manipulating those interfaces between liquids and surfaces through tuning the chemical and physical properties of the inner walls of the microchannel. Therefore, the microchannel inner surface design plays critical roles in regulating microflows to enhance the capabilities of microfluidic systems for various applications. Most recently, the rapid progresses in micro-/nanofabrication technologies and fundamental materials have also made it possible to integrate increasingly complex chemical and physical surface modification strategies with the preparation of microchannels in microfluidics. Besides, a wave of researches focusing on the ideas of using liquids as dynamic surface materials is identified, and the unique characteristics endowed with liquid-liquid interfaces have revealed that the interesting phenomena can extend the scope of interfacial interactions determining microflow behaviors. This review extensively discusses the microchannel inner surface designs for microflow control, especially evaluates them from the perspectives of the interfaces resulting from the inner surface designs. In addition, prospective opportunities for the development of surface designs of microchannels, and their applications are provided with the potential to attract scientific interest in areas related to the rapid development and applications of various microchannel systems

Liquid gating elastomeric porous system with dynamically controllable gas/liquid transport

【Abstract】The development of membrane technology is central to fields ranging from resource harvesting to medicine, but the existing designs are unable to handle the complex sorting of multiphase substances required for many systems. Especially, the dynamic multiphase transport and separation under a steady-state applied pressure have great benefits for membrane science, but have not been realized at present. Moreover, the incorporation of precisely dynamic control with avoidance of contamination of membranes remains elusive. We show a versatile strategy for creating elastomeric microporous membrane-based systems that can finely control and dynamically modulate the sorting of a wide range of gasesandliquids underasteady-stateapplied pressure,nearlyeliminate fouling,and can be easily applied over many size scales, pressures, and environments. Experiments and theoretical calculation demonstrate the stability of our system and the tunability of the critical pressure. Dynamic transport of gas and liquid can be achieved through our gating interfacial design and the controllable pores’ deformation without changing the applied pressure. Therefore, we believe that this system will bring new opportunities for many applications, such as gas-involved chemical reactions, fuel cells, multiphase separation, multiphase flow, multiphase microreactors, colloidal particle synthesis, and sizing nano/microparticles.This work was supported by the National Natural Science Foundation of China (grant no. 21673197), the Young Overseas High-level Talents Introduction Plan, the 111 Project (grant no. B16029). 研究工作得到国家自然科学基金委（项目批准号：21673197）和厦门大学校长基金（项目批准号：20720170050）等资助与支持

Altered metabolite levels and correlations in patients with colorectal cancer and polyps detected using seemingly unrelated regression analysis

Introduction: Metabolomics technologies enable the identification of putative biomarkers for numerous diseases; however, the influence of confounding factors on metabolite levels poses a major challenge in moving forward with such metabolites for pre-clinical or clinical applications. Objectives: To address this challenge, we analyzed metabolomics data from a colorectal cancer (CRC) study, and used seemingly unrelated regression (SUR) to account for the effects of confounding factors including gender, BMI, age, alcohol use, and smoking. Methods: A SUR model based on 113 serum metabolites quantified using targeted mass spectrometry, identified 20 metabolites that differentiated CRC patients (n = 36), patients with polyp (n = 39), and healthy subjects (n = 83). Models built using different groups of biologically related metabolites achieved improved differentiation and were significant for 26 out of 29 groups. Furthermore, the networks of correlated metabolites constructed for all groups of metabolites using the ParCorA algorithm, before or after application of the SUR model, showed significant alterations for CRC and polyp patients relative to healthy controls. Results: The results showed that demographic covariates, such as gender, BMI, BMI2, and smoking status, exhibit significant confounding effects on metabolite levels, which can be modeled effectively. Conclusion: These results not only provide new insights into addressing the major issue of confounding effects in metabolomics analysis, but also shed light on issues related to establishing reliable biomarkers and the biological connections between them in a complex disease

Dynamic air/liquid pockets for guiding microscale flow

Microscale flows of fluids are mainly guided either by solid matrices or by liquid–liquid interfaces. However, the solid matrices are plagued with persistent fouling problems, while liquid–liquid interfaces are limited to low-pressure applications. Here we report a dynamic liquid/solid/gas material containing both air and liquid pockets, which are formed by partially infiltrating a porous matrix with a functional liquid. Using detailed theoretical and experimental data, we show that the distribution of the air- and liquid-filled pores is responsive to pressure and enables the formation and instantaneous recovery of stable liquid–liquid interfaces that sustain a wide range of pressures and prevent channel contamination. This adaptive design is demonstrated for polymeric materials and extended to metal-based systems that can achieve unmatched mechanical and thermal stability. Our platform with its unique adaptive pressure and antifouling capabilities may offer potential solutions to flow control in microfluidics, medical devices, microscale synthesis, and biological assays

GLP-1 receptor agonist as a modulator of innate immunity

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid hormone secreted by L cells in the distal ileum, colon, and pancreatic α cells, which participates in blood sugar regulation by promoting insulin release, reducing glucagon levels, delaying gastric emptying, increasing satiety, and reducing appetite. GLP-1 specifically binds to the glucagon-like peptide-1 receptor (GLP-1R) in the body, directly stimulating the secretion of insulin by pancreatic β-cells, promoting proliferation and differentiation, and inhibiting cell apoptosis, thereby exerting a glycemic lowering effect. The glycemic regulating effect of GLP-1 and its analogues has been well studied in human and murine models in the circumstance of many diseases. Recent studies found that GLP-1 is able to modulate innate immune response in a number of inflammatory diseases. In the present review, we summarize the research progression of GLP-1 and its analogues in immunomodulation and related signal pathways

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD

Reticulation is a Risk Factor of Progressive Subpleural non-Fibrotic Interstitial Lung Abnormalities

Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular for subpleural non-fibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural non-fibrotic ILAs over time in a large health check-up population, and to identify how reticulation contributes to the risk of radiological progression. Methods: Based on ILAs definition by the Fleischner Society, low-dose chest CT images from community-dwelling population undergone health check-up were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural non-fibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend<0.0001). Of 454 individuals with subpleural non-fibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (OR 1.9; 95%CI 1.2-3.0, P=0.0040). No difference in radiological progression was identified between subpleural non-fibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%, P=0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural non-fibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural non-fibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs

Bioinspired Universal Flexible Elastomer-Based Microchannels

Flexible and stretchable microscale fluidic devices have a broad range of potential applications, ranging from electronic wearable devices for convenient digital lifestyle to biomedical devices. However, simple ways to achieve stable flexible and stretchable fluidic microchannels with dynamic liquid transport have been challenging because every application for elastomeric microchannels is restricted by their complex fabrication process and limited material selection. Here, a universal strategy for building microfluidic devices that possess exceptionally stable and stretching properties is shown. The devices exhibit superior mechanical deformability, including high strain (967%) and recovery ability, where applications as both strain sensor and pressure‐flow regulating device are demonstrated. Various microchannels are combined with organic, inorganic, and metallic materials as stable composite microfluidics. Furthermore, with surface chemical modification these stretchable microfluidic devices can also obtain antifouling property to suit for a broad range of industrial and biomedical applications.Chemistry and Chemical Biolog

Discovery of a high-altitude ecotype and ancient lineage of Arabidopsis thaliana from Tibet

Arabidopsis thaliana (A. thaliana) has long been a model species for dicotyledon study, and was the first flowering plant to get its genome completed sequenced [1]. Although most wild A. thaliana are collected in Europe, several studies have found a rapid A. thaliana west-east expansion from Central Asia [2]. The Qinghai-Tibet Plateau (QTP) is close to Central Asia and known for its high altitude, unique environments and biodiversity [3]. However, no wild-type A. thaliana had been either discovered or sequenced from QTP. Studies on the A. thaliana populations collected under 2000 m asl have shown that the adaptive variations associated with climate and altitudinal gradients [4]. Hence a high-altitude A. thaliana provides a precious natural material to investigate the evolution and adaptation process. Here, we present the genome of a new ecotype of A. thaliana collected in the Gongga County, Tibet (4200 m asl) (Fig. 1a), to demonstrate its evolutionary history and adaptation to highaltitude regions