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Background Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV- let-7a-5p ) derived from transfected Wharton’s jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. Methods A cellular nanoporation (CNP) method was used to induce the production and release of EV- let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV- let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV- let-7a-5p in a rat model of hyperoxia-induced ALI. Results The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV- let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV- let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV- let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. Conclusion This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p -enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D3), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the “Warburg effect” to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.

Background Colorectal cancer (CRC) poses a significant clinical challenge because of drug resistance, which can adversely impact patient outcomes. Recent research has shown that abnormalities within the tumor microenvironment, especially hyperglycemia, play a crucial role in promoting metastasis and chemoresistance, and thereby determine the overall prognosis of patients with advanced CRC. Methods This study employs data mining and consensus molecular subtype (CMS) techniques to identify pitavastatin and atorvastatin as potential agents for targeting high glucose-induced drug resistance in advanced CRC cells. CRC cells maintained under either low or high glucose conditions were established and utilized to assess the cytotoxic effects of pitavastatin and atorvastatin, both with and without 5-fluorouracil (5-FU). CRC 3D spheroids cultured were also included to demonstrate the anti-drug resistance of pitavastatin and atorvastatin. Results A bioinformatics analysis identified pitavastatin and atorvastatin as promising drug candidates. The CMS4 CRC cell line SW480 (SW480-HG) was established and cultured under high glucose conditions to simulate hyperglycemia-induced drug resistance and metastasis in CRC patients. Pitavastatin and atorvastatin could inhibit cell proliferation and 3D spheroid formation of CMS4 CRC cells under high glucose conditions. In addition, both pitavastatin and atorvastatin can synergistically promote the 5-FU-mediated cytotoxic effect and inhibit the growth of 5-FU-resistant CRC cells. Mechanistically, pitavastatin and atorvastatin can induce apoptosis and synergistically promote the 5-FU-mediated cytotoxic effect by activating autophagy, as well as the PERK/ATF4/CHOP signaling pathway while decreasing YAP expression. Conclusion This study highlights the biomarker-guided precision medicine strategy for drug repurposing. Pitavastatin and atorvastatin could be used to assist in the treatment of advanced CRC, particularly with CMS4 subtype CRC patients who also suffer from hyperglycemia. Pitavastatin, with an achievable dosage used for clinical interventions, is highly recommended for a novel CRC therapeutic strategy.

Inadequate vitamin D status may increase the risk of developing multiple types of cancer. Epidemiological studies suggest an inverse association between 25-hydroxyvitamin D3 (25(OH)D3) and malignancy, including colorectal cancer. Previous studies have suggested that MED28, a Mediator subunit involved in transcriptional regulation, is associated with the growth of colorectal cancer cells; however, its role in the progression of metastasis such as epithelial–mesenchymal transition (EMT) and cell migration of colorectal cancer is unclear at present. The aim of this study was to investigate a potentially suppressive effect of calcitriol, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a bioactive form of vitamin D, and the role of MED28 in the progression of EMT in human colorectal cancer cells. Suppression of MED28 increased the expression of E-cadherin and reduced the expression of several mesenchymal and migration biomarkers and Wnt/β-catenin signaling molecules, whereas overexpression of MED28 enhanced the EMT features. Calcitriol suppressed the expression of MED28, and the effect of calcitriol mirrored that of MED28 silencing. Our data indicate that calcitriol attenuated MED28-mediated cell growth and EMT in human colorectal cancer cells, underlining the significance of MED28 in the progression of colorectal cancer and supporting the potential translational application of calcitriol.

A C4F8/He inductively coupled plasma-reactive ion etching (ICP-RIE) was studied to improve the etching conditions of quartz glass. The influences of C4F8 flow rate, He flow rate, chamber pressure, inductively coupled plasma (ICP) power, bias power and cooling temperature were investigated. A report is presented on an optimum etching condition for fabricating quartz-based optical components considering their application in diffractive optical element (DOE) devices. As per these etching results, the etched microstructure exhibited a depth of 44.2 μm and a vertical sidewall angle of 89° resulting from an ICP power of 3000 W, a bias power of 200 W, a chamber pressure of 2.5 mTorr and an etching time of 120 min in a mixture of C4F8 and He gases with 30 and 100 sccm flow rates, respectively. The successful fabrication of the DOE component by ICP-RIE is reported. This can be used to provide the uniform light intensity distribution for a DOE device.

This study investigates the impact of global warming on drought/flood patterns in China at the end of the 21st century based on the simulations of 22 global climate models and a regional climate model （RegCM3） under the SRES （Special Report on Emissions Scenarios） A1B scenario. The standardized precipitation index （SPI）, which has well performance in monitoring the drought/ flood characteristics （in terms of their intensity, duration, and spatial extent） in China, is used in this study. The projected results of 22 coupled models and the RegCM3 simulation are consistent. These models project a decrease in the frequency of droughts in most parts of northern China and a slight increase in the frequency in some parts of southern China. Considering China as a whole, the spatial extents of droughts are projected to be signifi- cantly reduced. In contrast, future flood events over most parts of China are projected to occur more frequently with stronger intensity and longer duration than those prevalent currently. Additionally, the spatial extents of flood events are projected to significantly increase.

最近,NASA发布了一套基于CMIP5 21个耦合模式输出的高分辨率降尺度逐日数据集,简称NEX-GDDP。本文评估了NEX-GDDP对中国极端降水的模拟性能。研究发现:(1)相比CMIP5直接输出结果,NEX-GDDP能够更好刻画中国极端降水的空间分布;(2)未来中国极端降水事件明显增多、强度增强,NEX-GDDP在区域尺度上给出了更多的气候变化信息;(3)NEXGDDP预估的中国未来极端降水变化的不确定性范围相比CMIP5直接输出结果明显减少,使得预估结果更加可靠.

The characteristics of heavy precipitation occurrence in autumn (the month of September) over North China are investigated using daily observational data. Results indicate that heavy precipitation events experienced a significant decadal increase in 2000/2001. Further investigation reveals a close connection between heavy precipitation occurrence and simultaneous North Pacific SST. The SST anomaly over the North Pacific can result in intensification of the western North Pacific subtropical high and increased water vapor transport from the tropical ocean, which benefits the occurrence of heavy precipitation over North China. However, the key region of North Pacific SST influencing heavy precipitation events over North China was different in the periods 1960-2000 and 2001-2014, being located over the eastern Ocean to China in the first period but more eastward in the second period. This drift in the key region of SST is partly responsible for the decadal increase in heavy precipitation events over North China since 2000/2001. Additionally, the changes in SST variability (a decrease in the eastern Ocean to China and an increase to its east) may have been the main reason for the eastward movement of the key region in the latter period. Certainly, more work is needed in the future to verify the findings of this study.

Non-volatile resistive switching, also known as memristor1 effect, where an electric field switches the resistance states of a two-terminal device, has emerged as an important concept in the development of high-density information storage, computing and reconfigurable systems2–9. The past decade has witnessed substantial advances in non-volatile resistive switching materials such as metal oxides and solid electrolytes. It was long believed that leakage currents would prevent the observation of this phenomenon for nanometre-thin insulating layers. However, the recent discovery of non-volatile resistive switching in two-dimensional monolayers of transition metal dichalcogenide10,11 and hexagonal boron nitride12 sandwich structures (also known as atomristors) has refuted this belief and added a new materials dimension owing to the benefits of size scaling10,13. Here we elucidate the origin of the switching mechanism in atomic sheets using monolayer MoS2 as a model system. Atomistic imaging and spectroscopy reveal that metal substitution into a sulfur vacancy results in a non-volatile change in the resistance, which is corroborated by computational studies of defect structures and electronic states. These findings provide an atomistic understanding of non-volatile switching and open a new direction in precision defect engineering, down to a single defect, towards achieving the smallest memristor for applications in ultra-dense memory, neuromorphic computing and radio-frequency communication systems2,3,11.A combination of atomistic imaging and spectroscopy reveals that metal substitution into a sulfur vacancy is the underlying mechanism for resistive switching in transition metal dichalcogenide monolayers.

Wearable strain sensors that detect joint/muscle strain changes become prevalent at human–machine interfaces for full-body motion monitoring. However, most wearable devices cannot offer customizable opportunities to match the sensor characteristics with specific deformation ranges of joints/muscles, resulting in suboptimal performance. Adequate wearable strain sensor design is highly required to achieve user-designated working windows without sacrificing high sensitivity, accompanied with real-time data processing. Herein, wearable Ti 3 C 2 T x MXene sensor modules are fabricated with in-sensor machine learning (ML) models, either functioning via wireless streaming or edge computing, for full-body motion classifications and avatar reconstruction. Through topographic design on piezoresistive nanolayers, the wearable strain sensor modules exhibited ultrahigh sensitivities within the working windows that meet all joint deformation ranges. By integrating the wearable sensors with a ML chip, an edge sensor module is fabricated, enabling in-sensor reconstruction of high-precision avatar animations that mimic continuous full-body motions with an average avatar determination error of 3.5 cm, without additional computing devices. Wearable sensors with edge computing are desired for human motion monitoring. Here, the authors demonstrate a topographic design for wearable MXene sensor modules with wireless streaming or in-sensor computing models for avatar reconstruction.