Ammonium-derived nitrous oxide is a global source in streams.

Global riverine nitrous oxide (N2O) emissions have increased more than 4-fold in the last century. It has been estimated that the hyporheic zones in small streams alone may contribute approximately 85% of these N2O emissions. However, the mechanisms and pathways controlling hyporheic N2O production in stream ecosystems remain unknown. Here, we report that ammonia-derived pathways, rather than the nitrate-derived pathways, are the dominant hyporheic N2O sources (69.6 ± 2.1%) in agricultural streams around the world. The N2O fluxes are mainly in positive correlation with ammonia. The potential N2O metabolic pathways of metagenome-assembled genomes (MAGs) provides evidence that nitrifying bacteria contain greater abundances of N2O production-related genes than denitrifying bacteria. Taken together, this study highlights the importance of mitigating agriculturally derived ammonium in low-order agricultural streams in controlling N2O emissions. Global models of riverine ecosystems need to better represent ammonia-derived pathways for accurately estimating and predicting riverine N2O emissions.

17ß-estradiol promotes myeloid-derived suppressor cells functions and alleviates inflammatory bowel disease by activation of Stat3 and NF-κB signalings.

Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in prevalence. Estrogen has been previously shown to exert anti-inflammatory action in IBD development, however, the mechanisms remain obscure. Recent research has revealed that myeloid-derived suppressor cells (MDSCs) play a protective role in IBD pathogenesis. To investigate the molecular mechanisms of estrogen steroid 17ß-estradiol (E2) in IBD progression, we established IBD mouse models (DNB-induced) with or without prior ovariectomy (OVX) and E2 implantation. We found that OVX led to worse IBD symptoms and reduced MDSCs frequency, whereas E2 significantly alleviated these effects in vivo. Moreover, in vitro experiments showed that E2 promoted the proliferation and immunosuppressive function of MDSCs through phosphorylation of Stat3 and p65. Mechanistically, E2-mediated Stat3/p65 phosphorylation depends on the interaction between HOTAIR, a long non-coding RNA that are well-known in MDSCs proliferation, and Stat3/p65 respectively. In conclusion, our study revealed that E2 promotes the expansion and immunosuppressive function of MDSCs, and thus diminished the occurrence and development of IBD.

Combined diagnosis for Parkinson's disease via gait and eye movement disorders.

BACKGROUND AND OBJECTIVES: With the discovery of the potential role of gait and eye movement disorders in Parkinson's disease (PD) recognition, we intend to investigate the combined diagnostic value of gait and eye movement disorders for PD. METHODS: We enrolled some Chinese PD patients and healthy controls and separated them into the training and validation sets based on enrollment time. Performance in five oculomotor paradigms and in one gait paradigm was examined using an infrared eye tracking device and a wearable gait analysis device. We developed and validated a combined model for PD diagnosis via multivariate stepwise logistic regression analysis. Furthermore, subgroup comparisons and multi-model comparison were performed to assess its applicability and advantages. RESULTS: A total of 145 PD patients and 80 healthy controls in China were recruited. The pro-saccade velocity, the trunk-sway max, and the turn mean angular velocity were finally screened out for the model development. Incorporating age factor, the ternary model demonstrated more satisfactory performance on ROC (AUC of 0.953 in the training set and AUC of 0.972 in the validation set), calibration curve, and decision curve. A nomogram was drawn to visualize the model. The combined model outperforms individual models with a broad application and the unique diagnostic value for early detection of PD patients, especially TD-PD patients. CONCLUSION: We demonstrated the presence of gait and eye movement disorders, as well as the feasibility, applicability, and superiority of employing them together to diagnose PD.

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

Engineering of Cerium Modified TiNb2O7 Nanoparticles For Low-Temperature Lithium-Ion Battery.

Although TiNb2O7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li4Ti5O12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li+ and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g-1 at 100 mA g-1 after 100 cycles, and 183.0 mA h g-1 even under 3200 mA g-1. In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g-1 can still reach 89.7 mA h g-1, corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature.

Association of Monocyte Count With Lung Function and Exercise Capacity Among Hospitalized COVID-19 Survivors: A 2-Year Cohort Study.

BACKGROUND: Abnormal changes of monocytes have been observed in acute COVID-19, whereas associations of monocyte count with long COVID were not sufficiently elucidated. METHODS: A cohort study was conducted among COVID-19 survivors discharged from hospital. The primary outcomes were core symptoms of long COVID, distance walked in 6 min, and lung function, and the secondary outcomes were health-related quality of life and healthcare use after discharge. Latent variable mixture modeling was used to classify individuals into groups with similar trajectory of monocyte count from discharge to 2-year after symptom onset. Multivariable adjusted generalized linear regression models and logistic regression models were used to estimate the associations of monocyte count trajectories and monocyte count at discharge with outcomes. RESULTS: In total, 1389 study participants were included in this study. Two monocyte count trajectories including high to normal high and normal trajectory were identified. After multivariable adjustment, participants in high to normal high trajectory group had an odds ratio (OR) of 2.52 (95% CI, 1.44-4.42) for smell disorder, 2.27 (1.27-4.04) for 6-min walking distance less than lower limit of normal range, 2.45 (1.08-5.57) for total lung capacity (TLC) < 80% of predicted, 3.37 (1.16-9.76) for personal care problem, and 1.70 (1.12-2.58) for rehospitalization after discharge at 2-year follow-up compared with those in normal trajectory group. Monocyte count at discharge showed similar results, which was associated with smell disorder, TLC < 80% of predicted, diffusion impairment, and rehospitalization. CONCLUSIONS: Monocyte count may serve as an easily accessible marker for long-term management of people recovering from COVID-19.

High-performance, large-area flexible SERS substrates prepared by reactive ion etching for molecular detection.

In the realm of molecular detection, the surface-enhanced Raman scattering (SERS) technique has garnered increasing attention due to its rapid detection, high sensitivity, and non-destructive characteristics. However, conventional rigid SERS substrates are either costly to fabricate and challenging to prepare over a large area, or they exhibit poor uniformity and repeatability, making them unsuitable for inspecting curved object surfaces. In this work, we present a flexible SERS substrate with high sensitivity as well as good uniformity and repeatability. First, the flexible polydimethylsiloxane (PDMS) substrate is manually formulated and cured. SiO2/Ag layer on the substrate can be obtained in a single process by using ion beam sputtering. Then, reactive ion etching is used to etch the upper SiO2layer of the film, which directly leads to the desired densely packed nanostructure. Finally, a layer of precious metal is deposited on the densely packed nanostructure by thermal evaporation. In our proposed system, the densely packed nanostructure obtained by etching the SiO2layer directly determines the SERS ability of the substrate. The bottom layer of silver mirror can reflect the penetrative incident light, the spacer layer of SiO2and the top layer of silver thin film can further localize the light in the system, which can realize the excellent absorption of Raman laser light, thus enhancing SERS ability. In the tests, the prepared substrates show excellent SERS performance in detecting crystalline violet with a detection limit of 10-11M. The development of this SERS substrate is anticipated to offer a highly effective and convenient method for molecular substance detection.

Turning harmful Mn2+ to treasure: In-situ formed ε-MnO2 for removing heavy metals from acid mine drainage.

Acid mine drainage (AMD) contains high concentrations of heavy metals, causing serious environmental pollution. Current neutralization techniques fail to recover and utilize valuable heavy metals, and generate large quantities of hazardous sludge. Manganese (Mn) is generally present at high levels in AMD. Therefore, this paper proposed a technology to recover Mn from AMD, by adding KMnO4 to converting Mn into ε-MnO2. Ultra-Violet C (UVC) was used to photolyze the residual KMnO4. The study then evaluated the processes and mechanisms involved in the technology. The photolysis of KMnO4 in strong acidic conditions was determined, and new mechanisms were proposed. MnO2 produced by the photolysis process was formed through the reaction between Mn(III) and KMnO4. In the absence of KMnO4, Mn(III) underwent further photolysis and was reduced to Mn2+. The maximum adsorption capacities of in-situ formed ε-MnO2 for Pb2+, Cd2+, and Fe3+ were 449.80, 122.05, and 779.88 mg/g, respectively. Higher Mn-OH levels and MnO2 regeneration were crucial in improving adsorption performance. Proton exchange and inner-circle complexation were the main pathways for Pb2+ and Cd2+ adsorption by in-situ formed ε-MnO2. A phase transformation occurred when a substantial amount of Fe3+ was adsorbed, leading to the gradual transformation to MnFe binary oxides. When applying in-situ formed ε-MnO2 technology for actual AMD treatment, 98.62 % of Mn in AMD was recovered within 24 h in the presence of ε-MnO2 for possible further reuse in industries, with a final recovery of 0.76 kg/m3. Further, this technique removed other heavy metals and reduced the sludge volume by 20.99 % when used as a pre-treatment step for neutralization. These results demonstrated the broad potential of this treatment technology.

Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Modeling the pest-pathogen threats in a warming world for the red turpentine beetle (Dendroctonus valens) and its symbiotic fungus (Leptographium procerum).

BACKGROUND: Dendroctonus valens along with its symbiotic fungi have caused unprecedented damage to pines in China. Leptographium procerum, its primary symbiotic fungus, facilitates the invasion and colonization of the pest, thereby aggravating ecological threats. Assessing shifts in the niches and ranges of D. valens and its symbiotic fungus could provide a valuable basis for pest control. Here, we conducted niche comparisons between native and invasive populations of D. valens. Then, we employed standard ecological niche models and ensembles of small models to predict the potential distributions of D. valens and L. procerum under climate change conditions and to estimate areas of overlap. RESULTS: The niche of invasive population of D. valens in Chinese mainland only occupied a limited portion of the niche of native population in North America, leaving a substantial native niche unfilled and without any niche expansion. The suitable regions for D. valens are predicted in central and southern North America and central and northeastern Chinese mainland. The overlap with the suitable regions of L. procerum included eastern North America and the central and northeastern Chinese mainland under historical climatic scenarios. The regions susceptible to their symbiotic damage will shift northward in response to future climate change. CONCLUSIONS: Projected distributions of D. valens and its symbiotic fungus, along with areas vulnerable to their symbiotic damage, provide essential insights for devising strategies against this association. Additionally, our study contributes to comprehending how biogeographic approaches aid in estimating potential risks of pest-pathogen interactions in forests within a warming world. © 2024 Society of Chemical Industry.

Three-Dimensional Manipulation of Micromodules Using Twin Optothermally Actuated Bubble Robots.

A 3D manipulation technique based on two optothermally generated and actuated surface-bubble robots is proposed. A single laser beam can be divided into two parallel beams and used for the generation and motion control of twin bubbles. The movement and spacing control of the lasers and bubbles can be varied directly and rapidly. Both 2D and 3D operations of micromodules were carried out successfully using twin bubble robots. The cooperative manipulation of twin bubble robots is superior to that of a single robot in terms of stability, speed, and efficiency. The operational technique proposed in this study is expected to play an important role in tissue engineering, drug screening, and other fields.

Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial.

BACKGROUND: A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery. METHODS: In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18-80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions. DISCUSSION: Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.

Novel Operation Mechanism and Multifunctional Applications of Bubble Microrobots.

Microrobots have emerged as powerful tools for manipulating particles, cells, and assembling biological tissue structures at the microscale. However, achieving precise and flexible operation of arbitrary-shaped microstructures in 3D space remains a challenge. In this study, three novel operation methods based on bubble microrobots are proposed to enable delicate and multifunctional manipulation of various microstructures. These methods include 3D turnover, fixed-point rotation, and 3D ejection. By harnessing the combined principles of the effect of the heat flow field and surface tension of an optothermally generated bubble, the bubble microrobot can perform tasks such as flipping an SIA humanoid structure, rotating a bird-like structure, and launching a hollow rocket-like structure. The proposed multi-mode operation of bubble microrobots enables diverse attitude adjustments of microstructures with different sizes and shapes in both 2D and 3D spaces. As a demonstration, a biological microenvironment of brain glioblastoma is constructed by the bubble microrobot. The simplicity, versatility, and flexibility of this proposed method hold great promise for applications in micromanipulation, assembly, and tissue engineering.

Circ-SATB2 (hsa_circ_0008928) and miR-150-5p are regulators of TRIM66 in the regulation of NSCLC cell growth and metastasis of NSCLC cells via the ceRNA pathway.

Circular RNA (circRNA) was an important modulator and potential molecular target of nonsmall cell lung cancer (NSCLC). CircSATB2 was reported to be upregulated in NSCLC. However, the role and mechanism of circSATB2 in NSCLC progression remain to be illustrated. The RNA and protein expression was detected by quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry assay. Cell counting kit-8, cell colony formation, and 5-ethynyl-2'-deoxyuridine assays were applied to assess cell growth. The migrated and invaded cells were examined by transwell assay. Flow cytometry was performed to measure apoptotic cells. The interaction among circSATB2, microRNA-150-5p (miR-150-5p), and tripartite motif-containing protein 66 (TRIM66) was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. An in vivo experiment was conducted to investigate the effect of circSATB2 on tumor growth. CircSATB2 expression was highly expressed in NSCLC tissues and cell lines. CircSATB2 and TRIM66 silencing both suppressed NSCLC cell growth, migration, and invasion whereas promoted NSCLC cell apoptosis. CircSATB2 acted as a molecular sponge for miR-150-5p, and miR-150-5p interacted with the 3' untranslated region (3'UTR) of TRIM66. Moreover, circSATB2 knockdown-induced effects were partly reversed by TRIM66 overexpression in NSCLC cells. Besides, cirSATB2 expression was negatively correlated with miR-150-5p level and positively correlated with TRIM66 level in NSCLC tumor tissues. CircSATB2 knockdown blocked xenograft tumor growth in vivo. In summary, this study verified that circSATB2 stimulated NSCLC cell malignant behaviors by miR-150-5p/TRIM66 pathway, providing a possible circRNA-targeted therapy for NSCLC.

Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery.

Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.

Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring.

Bacillus Calmette-Guérin (BCG) vaccination induces a type of immune memory known as "trained immunity", characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27's higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces.

Pyroelectric-Effect-Assisted Near-Infrared-Driven Photoelectrochemical Biosensor Based on Exponential DNA Amplifier for MicroRNA Detection.

Although near-infrared responsive photoelectrochemical (PEC) biosensors have less damage to biological components compared to UV-visible light, they still reveal an inferior response due to the rapid recombination of photogenerated electron-hole. In this study, a near-infrared-driven PEC biosensor is fabricated for microRNA (miRNA) detection via integrating photoelectricity and pyroelectricity. Upon the introduction of target miRNA-21, the exponential DNA amplifier is triggered based on enzyme-assisted strand displacement amplification (SDA), releasing multiple Ag2S reporter probes to hybridize with capture probes immobilized on a CdS-2-mercaptobenzimidazole (2MBI)-modified photoelectrode. As a result, under the stimulation of NIR, the photoelectric conversion of Ag2S NPs generates the photocurrents. In addition, due to the strong hole acceptor ability of MBI, the pyroelectric effect of CdS-2MBI nanocomposites is enhanced, which generates highly pyroelectro-induced charge separation efficiency and induces the pyroelectric current benefited from the spontaneous polarization of CdS-2MBI caused by the temperature variation under the function of Ag2S nanoheaters. Impressively, this PEC biosensor has achieved the sensitive and selective determination of miRNA-21 with a detection limit as low as 54 fM. Overall, this NIR-driven PEC biosensor based on pyroelectric and photoelectric effects opens up a new horizon for bioanalysis and early disease diagnosis.

ADAMTS13 inhibits H2O2-induced human venous endothelial cell injury to attenuate deep-vein thrombosis by blocking the p38/ERK signaling pathway.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), a plasma metalloprotease that cleaves von Willebrand factor, acts as a critical regulator in normal hemostasis. This study was aimed to explore the role of ADAMTS13 in endothelial cell injury during DVT and the possible mechanism. First, human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2). Then, the mRNA and protein expressions of ADAMTS13 were evaluated with the reverse transcription-quantitative polymerase chain reaction and western blot. After treatment with recombinant ADAMTS13 (rADAMTS13; rA13), the viability and apoptosis of H2O2-induced HUVECs were assessed by cell counting kit-8 assay and terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining. In addition, the levels of prostaglandin F1-alpha, endothelin-1, and reactive oxygen species were detected using the enzyme-linked immunosorbent assay and dichloro-dihydro-fluorescein diacetate assay. The expressions of proteins related to p38/extracellular signal-regulated kinase (ERK) signaling pathway were estimated with the western blot. Then, p79350 (p38 agonist) was used to pretreat cells to analyze the regulatory effects of rA13 on p38/ERK signaling in H2O2-induced HUVEC injury. The results revealed that ADAMTS13 expression was significantly downregulated in H2O2-induced HUVECs. The reduced viability and increased apoptosis of HUVECs induced by H2O2 were revived by ADAMTS13. ADAMTS13 also suppressed the oxidative stress in HUVECs after H2O2 treatment. Besides, ADAMTS13 was found to block p38/ERK signaling pathway, and p79350 reversed the impacts of ADAMTS13 on the damage of HUVECs induced by H2O2. To sum up, ADAMTS13 could alleviate H2O2-induced HUVEC injury through the inhibition of p38/ERK signaling pathway.