Biological mitigation of soil nitrous oxide emissions by plant metabolites.

Plant metabolites significantly affect soil nitrogen (N) cycling, but their influence on nitrous oxide (N2O) emissions has not been quantitatively analyzed on a global scale. We conduct a comprehensive meta-analysis of 173 observations from 42 articles to evaluate global patterns of and principal factors controlling N2O emissions in the presence of root exudates and extracts. Overall, plant metabolites promoted soil N2O emissions by about 10%. However, the effects of plant metabolites on N2O emissions from soils varied with experimental conditions and properties of both metabolites and soils. Primary metabolites, such as sugars, amino acids, and organic acids, strongly stimulated soil N2O emissions, by an average of 79%, while secondary metabolites, such as phenolics, terpenoids, and flavonoids, often characterized as both biological nitrification inhibitors (BNIs) and biological denitrification inhibitors (BDIs), reduced soil N2O emissions by an average of 41%. The emission mitigation effects of BNIs/BDIs were closely associated with soil texture and pH, increasing with increasing soil clay content and soil pH on acidic and neutral soils, and with decreasing soil pH on alkaline soils. We furthermore present soil incubation experiments that show that three secondary metabolite types act as BNIs to reduce N2O emissions by 32%-45%, while three primary metabolite classes possess a stimulatory effect of 56%-63%, confirming the results of the meta-analysis. Our results highlight the potential role and application range of specific secondary metabolites in biomitigation of global N2O emissions and provide new biological parameters for N2O emission models that should help improve the accuracy of model predictions.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Construction of semiconductor nanocomposites for room-temperature gas sensors.

Gas sensors are essential for ensuring public safety and improving quality of life. Room-temperature gas sensors are notable for their potential economic benefits and low energy consumption, and their expected integration with wearable electronics, making them a focal point of contemporary research. Advances in nanomaterials and low-dimensional semiconductors have significantly contributed to the enhancement of room-temperature gas sensors. These advancements have focused on improving sensitivity, selectivity, and response/recovery times, with nanocomposites offering distinct advantages. The discussion here focuses on the use of semiconductor nanocomposites for gas sensing at room temperature, and provides a review of the latest synthesis techniques for these materials. This involves the precise adjustment of chemical compositions, microstructures, and morphologies. In addition, the design principles and potential functional mechanisms are examined. This is crucial for deepening the understanding and enhancing the operational capabilities of sensors. We also highlight the challenges faced in scaling up the production of nanocomposite materials. Looking ahead, semiconductor nanocomposites are expected to drive innovation in gas sensor technology due to their carefully crafted design and construction, paving the way for their extensive use in various sectors.

Electrochemical protein biosensors for disease marker detection: progress and opportunities.

The development of artificial intelligence-enabled medical health care has created both opportunities and challenges for next-generation biosensor technology. Proteins are extensively used as biological macromolecular markers in disease diagnosis and the analysis of therapeutic effects. Electrochemical protein biosensors have achieved desirable specificity by using the specific antibody-antigen binding principle in immunology. However, the active centers of protein biomarkers are surrounded by a peptide matrix, which hinders charge transfer and results in insufficient sensor sensitivity. Therefore, electrode-modified materials and transducer devices have been designed to increase the sensitivity and improve the practical application prospects of electrochemical protein sensors. In this review, we summarize recent reports of electrochemical biosensors for protein biomarker detection. We highlight the latest research on electrochemical protein biosensors for the detection of cancer, viral infectious diseases, inflammation, and other diseases. The corresponding sensitive materials, transducer structures, and detection principles associated with such biosensors are also addressed generally. Finally, we present an outlook on the use of electrochemical protein biosensors for disease marker detection for the next few years.

A miniprotein receptor electrochemical biosensor chip based on quantum dots.

Recently protein binders have emerged as a promising substitute for antibodies due to their high specificity and low cost. Herein, we demonstrate an electrochemical biosensor chip through the electronic labelling strategy using lead sulfide (PbS) colloidal quantum dots (CQDs) and the unnatural SARS-CoV-2 spike miniprotein receptor LCB. The unnatural receptor can be utilized as a molecular probe for the construction of CQD-based electrochemical biosensor chips, through which the specific binding of LCB and the spike protein is transduced to sensor electrical signals. The biosensor exhibits a good linear response in the concentration range of 10 pg mL-1 to 1 µg mL-1 (13.94 fM to 1.394 nM) with the limit of detection (LOD) being 3.31 pg mL-1 (4.607 fM for the three-electrode system) and 9.58 fg mL-1 (0.013 fM for the HEMT device). Due to the high sensitivity of the electrochemical biosensor, it was also used to study the binding kinetics between the unnatural receptor LCB and spike protein, which has achieved comparable results as those obtained with commercial equipment. To the best of our knowledge, this is the first example of using a computationally designed miniprotein receptor based on electrochemical methods, and it is the first kinetic assay performed with an electrochemical assay alone. The miniprotein receptor electrochemical biosensor based on QDs is desirable for fabricating high-throughput, large-area, wafer-scale biochips.

Protocol to capture transcription factor-mediated 3D chromatin interactions using affinity tag-based BL-HiChIP.

Pioneer transcription factors (TFs) can directly establish higher-order chromatin interactions to instruct gene transcription. Here, we present a protocol for capturing TF-mediated 3D chromatin interactions using affinity tag-based bridge linker (BL)-Hi-chromatin immunoprecipitation (HiChIP). We describe steps for constructing FLAG-tagged TF, performing BL-HiChIP, and preparing the library. We then detail procedures for sequencing, data analysis, and quality control. This protocol has potential applications in 3D chromatin analysis centered on any specific TF in any type of cells without the need of optimal antibodies. For complete details on the use and execution of this protocol, please refer to Ren et al. (2022).1.

Identification of oogonial stem cells in chicken ovary.

OBJECTIVES: Oogonial stem cells (OSCs) are germ cells that can sustain neo-oogenesis to replenish the pool of primary follicles in adult ovaries. In lower vertebrates, fresh oocytes are produced by numerous OSCs through mitosis and meiosis during each reproduction cycle, but the OSCs in adult mammals are rare. The birds have retained many conserved features and developed unique features of ovarian physiology during evolution, and the presence of OSCs within avian species remain unknown. MATERIALS AND METHODS: In this study, we investigated the existence and function of OSCs in adult chickens. The chicken OSCs were isolated and expanded in culture. We then used cell transplantation system to evaluate their potential for migration and differentiation in vivo. RESULTS: DDX4/SSEA1-positive OSCs were identified in both the cortex and medulla of the adult chicken ovary. These putative OSCs undergo meiosis in the reproductively active ovary. Furthermore, the isolated OSCs were expanded in vitro for months and found to express germline markers similar to those of primordial germ cells. When transplanted into the bloodstream of recipient embryos, these OSCs efficiently migrated into developing gonads, initiated meiosis, and then derived oocytes in postnatal ovaries. CONCLUSIONS: This study has confirmed the presence of functional OSCs in birds for the first time. The identification of chicken OSCs has great potential for improving egg laying and preserving endangered species.

Hollow-Out Fe2O3-Loaded NiO Heterojunction Nanorods Enable Real-Time Exhaled Ethanol Monitoring under High Humidity.

The analysis of exhaled breath has opened up new exciting avenues in medical diagnostics, sleep monitoring, and drunk driving detection. Nevertheless, the detection accuracy is greatly affected due to high humidity in the exhaled breath. Here, we propose a regulation method to solve the problem of humidity adaptability in the ethanol-monitoring process by building a heterojunction and hollow-out nanostructure. Therefore, large specific surface area hollow-out Fe2O3-loaded NiO heterojunction nanorods assembled by porous ultrathin nanosheets were prepared by a well-tailored interface reaction. The excellent response (51.2 toward 10 ppm ethanol at 80% relative humidity) and selectivity to ethanol under high relative humidity with a lower operating temperature (150 °C) were obtained, and the detection limit was as low as 0.5 ppb with excellent long-term stability. The superior gas-sensing performance was attributed to the high surface activity of the heterojunction and hollow-out nanostructure. More importantly, GC-MS, diffuse reflectance Fourier transform infrared spectroscopy, and DFT were utilized to analyze the mechanisms of heterojunction sensitization, ethanol-sensing reaction, and high-humidity adaptability. Our integrated low-power MEMS Internet of Things (IoT) system based on Fe2O3@NiO successfully demonstrates the functional verification of ethanol detection in human exhalation, and the integrated voice alarm and IoT positioning functions are expected to solve the problem of real-time monitoring and rapid initial screening of drunk driving. Overall, this novel method plays a vital role in areas such as control of material morphology and composition, breath analysis, gas-sensing mechanism research, and artificial olfaction.

Flexible Amperometric Immunosensor Based on Colloidal Quantum Dots for Detecting the Myeloperoxidase (MPO) Systemic Inflammation Biomarker.

Myeloperoxidase (MPO) has been demonstrated to be a biomarker of neutrophilic inflammation in various diseases. Rapid detection and quantitative analysis of MPO are of great significance for human health. Herein, an MPO protein flexible amperometric immunosensor based on a colloidal quantum dot (CQD)-modified electrode was demonstrated. The remarkable surface activity of CQDs allows them to bind directly and stably to the surface of proteins and to convert antigen-antibody specific binding reactions into significant currents. The flexible amperometric immunosensor provides quantitative analysis of MPO protein with an ultra-low limit of detection (LOD) (31.6 fg mL-1), as well as good reproducibility and stability. The detection method is expected to be applied in clinical examination, POCT (bedside test), community physical examination, home self-examination and other practical scenarios.

Single-Atom Cu Stabilized on Ultrathin WO2.72 Nanowire for Highly Selective and Ultrasensitive ppb-Level Toluene Detection.

Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ-annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra /Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single-atom catalysts (SACs)-containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic-level interface regulation engineering of WO2.72 nanowire-supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.

BACKGROUND: Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects. METHODS: Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats. RESULTS: Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies. CONCLUSION: ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.

[Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial].

OBJECTIVE: To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. RESULTS: Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre-treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). CONCLUSION: The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted.

Syringic acid from rice roots inhibits soil nitrification and N2O emission under red and paddy soils but not a calcareous soil.

Syringic acid (SA) is a novel biological nitrification inhibitor (BNIs) discovered in rice root exudates with significant inhibition of Nitrosomonas strains. However, the inhibitory effect of SA on nitrification and nitrous oxide (N2O) emissions in different soils and the environmental factors controlling the degree of inhibition have not been studied. Using 14-day microcosm incubation, we investigated the effects of different concentrations of SA on nitrification activity, abundance of ammonia-oxidizing microorganisms, and N2O emissions in three typical agricultural soils. The nitrification inhibitory efficacy of SA was strongest in acidic red soil, followed by weakly acidic paddy soil, with no significant effect in an alkaline calcareous soil. Potential nitrification activity (PNA) were also greatly reduced by SA additions in paddy and red soil. Pearson correlation analysis showed that the inhibitory efficacy of SA might be negatively correlated with soil pH and positively correlated with clay percentage. SA treatments significantly reduced N2O emissions by 69.1-79.3% from paddy soil and by 40.8%-46.4% from red soil, respectively, but no effect was recorded in the calcareous soil. SA addition possessed dual inhibition of both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) abundance in paddy and red soil. Structural equation modelling revealed that soil ammonium (NH4 +) and dissolved organic carbon content (DOC) were the key variables explaining AOA and AOB abundance and subsequent N2O emissions. Our results support the potential for the use of the BNI SA in mitigating N2O emissions and enhancing N utilization in red and paddy soils.

Oct4 dependent chromatin activation is required for chicken primordial germ cell migration.

Primordial germ cells (PGCs) are the undifferentiated progenitors of the gametes. Unlike the poor maintenance of cultured mammalian PGCs, the avian PGCs can be expanded in vitro indefinitely while preserving pluripotency and germline competence. In mammals, the Oct4 is the master transcription factor that ensures the stemness of pluripotent cells such as PGCs, but the specific function of Oct4 in chicken PGCs remains unclear. As expected, the loss of Oct4 in chicken PGCs reduced the expression of key pluripotency factors and promoted the genes involved in endoderm and ectoderm differentiation. Furthermore, the global active chromatin was reduced as shown by the depletion of the H3K27ac upon Oct4 suppression. Interestingly, the de-activated chromatin caused the down-regulation of adjacent genes which are mostly known regulators of cell junction, chemotaxis and cell migration. Consequently, the Oct4-deficient PGCs show impaired cell migration and could not colonize the gonads when re-introduced into the bloodstream of the embryo. We propose that, in addition to maintaining pluripotency, the Oct4 mediated chromatin activation is dictating chicken PGC migration.

All-solid-state SARS-CoV-2 protein biosensor employing colloidal quantum dots-modified electrode.

Rapid and reliable detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody can provide immunological evidence in addition to nucleic acid test for the early diagnosis and on-site screening of coronavirus disease 2019 (COVID-19). All-solid-state biosensor capable of rapid, quantitative SARS-CoV-2 antibody testing is still lacking. Herein, we propose an electronic labelling strategy of protein molecules and demonstrate SARS-CoV-2 protein biosensor employing colloidal quantum dots (CQDs)-modified electrode. The feature current peak corresponding to the specific binding reaction of SARS-CoV-2 antigen and antibody proteins was observed for the first time. The unique charging and discharging effect depending on the alternating voltage applied was ascribed to the quantum confinement, Coulomb blockade and quantum tunneling effects of quantum dots. CQDs-modified electrode could recognize the specific binding reaction between antigen and antibody and then transduce it into significant electrical current. In the case of serum specimens from COVID-19 patient samples, the all-solid-state protein biosensor provides quantitative analysis of SARS-CoV-2 antibody with correlation coefficient of 93.8% compared to enzyme-linked immunosorbent assay (ELISA) results. It discriminates patient and normal samples with accuracy of about 90%. The results could be read within 1 min by handheld testing system prototype. The sensitive and specific protein biosensor combines the advantages of rapidity, accuracy, and convenience, facilitating the implement of low-cost, high-throughput immunological diagnostic technique for clinical lab, point-of-care testing (POCT) as well as home-use test.

Y-2 reduces oxidative stress and inflammation and improves neurological function of collagenase-induced intracerebral hemorrhage rats.

Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+)-borneol, is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma. Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.

Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic stroke.

BACKGROUND: Ischemic stroke is a multifactorial disease contributing to mortality and neurological dysfunction. Isoliquiritin (ISL) has been reported to possess a series of pharmacological activities including antioxidant, anti-inflammatory, antifungal, anti-depression, anti-neurotoxicity and pro-angiogenesis activities but whether it can be used for ischemic stroke treatment remains unknown. PURPOSE: The goal of this study is to explore its therapeutic effect on ischemic stroke and demonstrated the potential mechanism of ISL in zebrafish model. METHODS: Using the photothrombotic-induced adult zebrafish model of ischemic stroke, we visualized the telencephalon (Tel) and optic tectum (OT) infarction injury at 24 h post-light exposure for 30 min by TTC and H&E staining. The effect of ISL on neurological deficits was analyzed during open tank swimming by video tracking. The antioxidant activity against ischemia injury was quantified by SOD, GSH-Px and MDA assay. Transcriptome analysis of zebrafish Tel revealed how ISL regulating gene expression to exert protective effect, which were also been validated by real-time quantitative PCR assays. RESULTS: We found for the first time that the Tel tissue was the first damaged site of the whole brain and it showed more sensitivity to the brain ischemic damage compared to the OT. ISL reduced the rate of Tel injury, ameliorated neurological deficits as well as counteracted oxidative damages by increasing SOD, GSH-Px and decreasing MDA activity. GO enrichment demonstrated that ISL protected membrane and membrane function as well as initiate immune regulation in the stress response after ischemia. KEGG pathway analysis pointed out that immune-related pathways, apoptosis as well as necroptosis pathways were more involved in the protective mechanism of ISL. Furthermore, the log2 fold change in expression pattern of 25 genes detected by qRT-PCR was consistent with that by RNA-seq. CONCLUSIONS: Tel was highly sensitive to the brain ischemia injury in zebrafish model of ischemic stroke. ISL significantly exerted protective effect on Tel injury, neurological deficits and oxidative damages. ISL could regulate a variety of genes related to immune, apoptosis and necrosis pathways against complex cascade reaction after ischemia. These findings enriched the study of ISL, making it a novel multi-target agent for ischemic stroke treatment.

Does pre-existent physical inactivity have a role in the severity of COVID-19?

BACKGROUND AND AIMS: Physical inactivity is considered an important lifestyle factor for overweight and cardiovascular disease. We aimed to investigate the association between pre-existent physical inactivity and the risk of severe coronavirus disease 2019 (COVID-19). METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 who were admitted between 15 February and 14 March 2020 in this retrospective study. We evaluated the association between pre-existent physical inactivity and severe COVID-19 using a logistic regression model. RESULTS: Of 164 eligible patients with COVID-19, 103 (62.8%) were reported to be physically inactive. Univariable logistic regression analysis showed that physical inactivity was associated with an increased risk of severe COVID-19 [unadjusted odds ratio (OR) 6.53, 95% confidence interval (CI) 1.88-22.62]. In the multivariable regression analysis, physical inactivity remained significantly associated with an increased risk of severe COVID-19 (adjusted OR 4.12, 95% CI 1.12-15.14) after adjustment for age, sex, stroke, and overweight. CONCLUSION: Our data showed that pre-existent physical inactivity was associated with an increased risk of experiencing severe COVID-19. Our findings indicate that people should be encouraged to keep physically active to be at a lower risk of experiencing a severe illness when COVID-19 infection seems unpredicted.The reviews of this paper are available via the supplemental material section.

Template-Free Construction of Tin Oxide Porous Hollow Microspheres for Room-Temperature Gas Sensors.

Porous hollow microsphere (PHM) materials represent ideal building blocks for realizing diverse functional applications such as catalysis, energy storage, drug delivery, and chemical sensing. This has stimulated intense efforts to construct metal oxide PHMs for achieving highly sensitive and low-power-consumption semiconductor gas sensors. Conventional methods for constructing PHMs rely on delicate reprogramming of templates and may suffer from the structural collapse issue during the removal of templates. Here, we propose a template-free method for the construction of tin oxide (SnO2) PHMs via the competition between the solvent evaporation rate and the phase separation dynamics of colloidal SnO2 quantum wires. The SnO2 PHMs (typically 3 ± 0.5 µm diameter and approximately 200 nm shell thickness) exhibit desirable structural stability with desirable processing compatibility with various substrates. This enables the realization of NO2 gas sensors having a superior response and recovery process at room temperature. The superior NO2-sensing characteristic is attributed to the effective gas adsorption competition on solid surfaces benefiting from efficient diffusion channels, enhancing the interaction of metal oxide solids with gas molecules in terms of the receptor function, transducer function, and utility factor. In addition, the one-step deposition of SnO2 PHMs directly onto device substrates simplifies the fabrication conditions for semiconductor gas sensors. The desirable structural stability of PHMs combined with the functional diversity of metal oxides may open new opportunities for the design of functional materials and devices.

SCR-1693 inhibits tau phosphorylation and improves insulin resistance associated cognitive deficits.

Except for few symptoms-improved drugs for Alzheimer's disease (AD), no disease-modified drug has been developed, especially for AD in type 2 diabetes mellitus (T2DM). SCR-1693, a disease-mortified candidate for AD, which is now in Phase I clinical study in China, improves Aß25-35-impaired cognitive function in rodent's models. Here we report the effect of SCR-1693 on regulation of tau phosphorylation and insulin resistance associated cognition, and illustrate its underlying mechanism. We found that in intracerebroventricular injection of streptozotcin (STZ) rats, oral administration of SCR-1693 dose-dependently improved the learning and memory in Morris water maze test, decreased tau hyperphosphorylation, astrogliosis and postsynaptic protein loss in hippocampus. In Neura-2a cells with stable transfection of full-length human tau (Neura-2a-tau), treatment of SCR-1693 concentration-dependently enhanced the activation of protein phosphatase (PP1) and protein phosphatase 2A (PP2A), decreased cellular tau phosphorylation, and increased insulin-induced cellular signaling to reverse insulin resistance. Pre-treatment with the inhibitor of PP1 and PP2A inhibited the effect of SCR-1693 on both of tau phosphorylation and insulin signaling in Neura-2a-tau cells. All data suggest that an increase of activity of tau phosphatase was involved in the mechanism of SCR-1693 on the regulation of tau phosphorylation and insulin signaling, and SCR-1693 is considerable candidate for insulin resistance associated sporadic AD.