Nonderivatized Method for the Detection of Perfluoroalkane Sulfonyl Fluorides by Liquid Chromatography-Microwave Plasma Torch Ionization Mass Spectrometry.

Per- and polyfluoroalkyl substances (PFAS) have caused widespread environmental concern in recent years. Among them, the levels of perfluoroalkane sulfonyl fluorides (PFASFs) in the environment have rarely been reported due to the lack of sensitive analytical methods. Herein, a novel liquid chromatography-microwave plasma torch ionization-mass spectrometry (LC-MPTI-MS) technique was designed for the direct analysis of PFASFs in the environment. The collaborative action of reactive oxygen species (such as hydroxyl radicals) and the elevated temperature within the ambient MPTI environment results in the replacement of the fluorine atom in sulfonyl fluoride by oxygen, leading to the detection of perfluoroalkanesulfonic acid (PFSA) ions by MS. Concurrently, LC was employed to separate other PFSAs that are present in the environment. Three PFASFs exhibited good linearity within the range of 1-500 µg/L with R2 > 0.994. The limit of detections (LODs) and the limit of quantifications (LOQs) were measured at 39.32-87.87 and 131.07-292.90 ng/L, respectively. The method was utilized for the direct detection of spiked perfluorooctane sulfonyl fluoride (PFOSF) in wastewater with recoveries of 77.16 to 124.81%. Our approach circumvents the laborious process of chemical derivatization and is anticipated to serve as a robust tool for determining the levels and behaviors of PFASFs in the environment.

PLD2 deficiency alleviates endothelial glycocalyx degradation in LPS-induced ARDS/ALI.

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2-/-) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1ß) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.

Unraveling EGFR-TKI resistance in lung cancer with high PD-L1 or TMB in EGFR-sensitive mutations.

BACKGROUND: Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms. METHODS: Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups. RESULTS: TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p < 0.001) and high TMB group (31% versus 13%, p < 0.05). Notably, PIK3CA and PTEN mutations emerged as the most important differentially mutated genes within the PI3K signaling pathway. CONCLUSIONS: Our findings reveal that the presence of PI3K signaling pathway mutations may be responsible for inducing primary resistance to EGFR-TKIs in NSCLC patients with EGFR-sensitive mutations along with high PD-L1 expression or high TMB. This finding is of great significance in guiding subsequent precision treatments in NSCLC.

Precise Modulation of the Coordination Environment of Single Cu Site Catalysts to Regulate the Peroxymonosulfate Activation Pathway for Water Remediation.

Single atom site catalysts (SACs) with atomically dispersed active sites can be expected to be potential ideal catalysts for accurately modulating the persulfate activation pathway during the water remediation process because of their well-defined structure and the maximum metallic atom utilization. In this paper, a series of Cu SACs with different coordination environments were synthesized to elaborately regulate the peroxymonosulfate activation pathway in AOPs to clarify active species generation and transformation in water remediation. The degradation rate constants (kobs) of Cu-N2, Cu-N3, and Cu-N4 were 0.028, 0.021, and 0.015 min-1, respectively. Cu-N2 SACs exhibited a noticeable enhanced performance for bisphenol A (BPA) removal from water compared to that of the Cu-Nx SACs (x = 3, 4), accompanied by peroxymonosulfate (PMS) activation pathway variation. As shown by experimental and theoretical results, the PMS activation pathway was transformed from ROS to electron transfer with nitrogen coordination numbers decreasing from 4 to 2, which can be ascribed to the uneven charge distribution of Cu sites as well as upshifts in the d-band center, and thereby optimized electron transfer for PMS activation. Furthermore, the increasing nitrogen vacancies of single Cu site catalysts can also result in more unoccupied 3d orbitals of Cu atoms in SACs, thereby improving the intermediates' (PMS and BPA) adsorption-desorption process and BPA removal performance. These findings provided a beneficial approach for the coordination number regulation of SACs in water remediation.

Enhanced photocatalytic performance of Bi2O2CO3/Bi4O5Br2/reduced graphene oxide Z-schemehe terojunction via a one-pot room-temperature synthesis.

Bi2O2CO3(BOC)/Bi4O5Br2(BOB)/reduced graphene oxide (rGO) Z-scheme heterojunction with promising photocatalytic properties was synthesized via a facile one-pot room-temperature method. Ultra-thin nanosheets of BOC and BOB were grown in situ on rGO. The formed 2D/2D direct Z-scheme heterojunction of BOC/BOB with oxygen vacancies (OVs) effectively leads to lower negative electron reduction potential of BOB as well as higher positive hole oxidation potential of BOC, showing improved reduction/oxidation ability. Particularly, rGO is an acceptor of the electrons from the conduction band of BOC. Its dual roles significantly improve the transfer performance of photo-induced charge carriers and accelerate their separation. With layered nanosheet structure, rich OVs, high specific surface area, and increased utilization efficiency of visible light, the multiple synergistic effects of BOC/BOB/rGO can achieve effective generation and separation of the electron-holes, thereby generating more •O2- and h+. The photocatalytic reduction efficiency of CO2 to CO (12.91 µmol/(g·hr)) is three times higher than that of BOC (4.18 µmol/(g·hr)). Moreover, it also achieved almost 100% removal of Rhodamine B and cyanobacterial cells within 2 hours.

High-Throughput Microfluidic Production of Droplets and Hydrogel Microspheres through Monolithically Integrated Microchannel Plates.

In this paper, we present a highly effective microfluidic emulsion system using an integrated microchannel plate (MCP), a porous glass membrane that is readily available and densely packs millions of through-microchannels, for high-throughput production of monodisperse droplets. The physical controls of droplet formation, including viscosity, flow rate, and pore size, have been extensively explored for optimum emulsification conditions. The performance of the device has been validated where monodisperse droplets with a narrow coefficient of variance (<5%) can be achieved at a dispersed phase flux of 3 mL h-1 from a piece of 4 × 4 mm2 MCP. The average droplet size is two times the nominal membrane pore diameter and thus can be easily controlled by choosing the appropriate membrane type. The preparation of hydrogel microspheres has also been demonstrated with a high throughput of 1.5 × 106 particles min-1. These microspheres with a uniform size range and rough surface morphology provide suitable bioenvironments and serve as ideal carriers for cell culture. Mouse fibroblasts are shown to be cultured on these 3D scaffolds with an average cell viability of over 96%. The cell attachment rate can reach up to 112 ± 7% in 24 h and the proliferation ability increases with the number of culture days. Furthermore, the device has been applied in the droplet digital polymerase chain reaction for absolute quantification of lung cancer-related PLAU genes. The detection limit achieved was noted to be 0.5 copies/µL with a dynamic range of 105 ranging from 1 × 102 to 1 × 106 copies/µL. Given the easy fabrication, robust performance, and simple operation, the emulsion system sets the stage for the laboratory's droplet-based assays and applications in tissue engineering.

Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury.

This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.

The importance of temperature monitoring in predicting wound healing.

CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.

Children's Pain Identification Based on Skin Potential Signal.

Pain management is a crucial concern in medicine, particularly in the case of children who may struggle to effectively communicate their pain. Despite the longstanding reliance on various assessment scales by medical professionals, these tools have shown limitations and subjectivity. In this paper, we present a pain assessment scheme based on skin potential signals, aiming to convert subjective pain into objective indicators for pain identification using machine learning methods. We have designed and implemented a portable non-invasive measurement device to measure skin potential signals and conducted experiments involving 623 subjects. From the experimental data, we selected 358 valid records, which were then divided into 218 silent samples and 262 pain samples. A total of 38 features were extracted from each sample, with seven features displaying superior performance in pain identification. Employing three classification algorithms, we found that the random forest algorithm achieved the highest accuracy, reaching 70.63%. While this identification rate shows promise for clinical applications, it is important to note that our results differ from state-of-the-art research, which achieved a recognition rate of 81.5%. This discrepancy arises from the fact that our pain stimuli were induced by clinical operations, making it challenging to precisely control the stimulus intensity when compared to electrical or thermal stimuli. Despite this limitation, our pain assessment scheme demonstrates significant potential in providing objective pain identification in clinical settings. Further research and refinement of the proposed approach may lead to even more accurate and reliable pain management techniques in the future.

Pollution Status and Associated Risk Assessment of Heavy Metals in Sewage Sludge in the Yangtze River Delta, China.

The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.

One-step preparation of a novel graphitic biochar/Cu0/Fe3O4 composite using CO2-ambiance pyrolysis to activate peroxydisulfate for dye degradation.

Herein, a one-step co-pyrolysis protocol was adopted for the first time to prepare a novel pyrogenic carbon-Cu0/Fe3O4 heteroatoms (FCBC) in CO2 ambiance to discern the roles of each component in PDS activation. During co-pyrolysis, CO2 catalyzed formation of reducing gases by biomass which facilitated reductive transformation of Fe3+ and Cu2+ to Cu0 and Fe3O4, respectively. According to the analysis, the resulting metal (oxide) catalyzed graphitization of biocharand decomposition of volatile substances resulting in an unprecedented surface area (1240 m2/g). The resulting FCBC showed greater structural defects and less electrical impedance. Batch experiments indicated that Rhodamine B (RhB) degradation by FCBC (100%) was superior to Fe3O4 (50%) and Cu0/Fe3O4 (76.4%) in persulfate (PDS) system, which maintained reasonable efficiency (75.6%-63.6%) within three cycles. The reactive oxygen species (ROS) associated with RhB degradation was identified by an electron paramagnetic resonance and confirmed by scavenging experiments. RhB degradation invoked both (sulfate and dominantly hydroxyl) radical and non-radical (singlet oxygen, 1O2) pathways. Regarding FCBC, Cu0 can continuously react with Fe3+ in Fe3O4 to generate larger quantities of Fe2+, and both Cu0 and Fe2+ activated PDS to yield sulfate radicals which was quickly converted to hydroxyl radical. Besides, Cu0/Cu2+ could complex with PDS to form a metastable complex, which particularly contributed to 1O2 generation. These cascade reactions by FCBC were reinforced by carbonyl group of biochar and favorable electron transfer ability. This work highlighted a new approach to prepare a magnetic and environment-benign heterogonous catalyst to remove organic pollutants in water.

Arc-Induced Nitrate Reagent Ion for Analysis of Trace Explosives on Surfaces Using Atmospheric Pressure Arc Desorption/Ionization Mass Spectrometry.

This study presents the rapid surface detection of explosives by employing atmospheric pressure arc desorption/ionization mass spectrometry (APADI-MS) using point-to-plane arc discharge. In APADI, neutral explosives readily bind to the gas-phase nitrate ion, NO3-, induced by arc discharge to form anionic adducts [M+NO3]-. This avoids the need for inorganic anionic additives such as NO3-, NO2-, Cl-, acetate, and trifluoroacetate for unique explosive ionization pathways and simplifies mass spectra. The analytical performance of APADI was thoroughly evaluated for the rapid detection of 10 explosives at levels in the range of 800 fg-1 µg. Arc-induced nitrogen oxide anions promoted the formation of characteristic adducts, such as [M+NO3]-, and improved the instrument response for all the explosives tested. APADI showed considerable sensitivity in the negative ion mode with limits of detection in the low picogram range, particularly when explosives were analyzed on a copper or aluminum foil substrate. APADI coupled with an Orbitrap mass spectrometer displayed a good linear response for the studied explosives. The linearity and intraday and interday precisions were evaluated, demonstrating the feasibility and robustness of APADI-MS for the detection of trace explosives on solid surfaces. The mechanisms of APADI for explosive ionization and desorption were examined and verified by performing density functional theory calculations.

Catalyst-Free Oxidation Reactions in a Microwave Plasma Torch-Based Ion/Molecular Reactor: An Approach for Predicting the Atmospheric Oxidation of Pollutants.

The atmospheric oxidation of chemicals has produced many new unpredicted pollutants. A microwave plasma torch-based ion/molecular reactor (MPTIR) interfacing an online mass spectrometer has been developed for creating and monitoring rapid oxidation reactions. Oxygen in the air is activated by the plasma into highly reactive oxygen radicals, thereby achieving oxidation of thioethers, alcohols, and various environmental pollutants on a millisecond scale without the addition of external oxidants or catalysts (6 orders of magnitude faster than bulk). The direct and real-time oxidation products of polycyclic aromatic hydrocarbons and p-phenylenediamines from the MPTIR match those of the long-term multistep environmental oxidative process. Meanwhile, two unreported environmental compounds were identified with an MPTIR and measured in the actual water samples, which demonstrates the considerable significance of the proposed device for both predicting the environmental pollutants (non-target screening) and studying the mechanism of atmospheric oxidative processes.

Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells.

BACKGROUND: Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD). METHODS: Male C57BL/6 mice were fed with a Lieber-DeCarli diet containing 5% alcohol for four weeks to establish a model of alcohol-induced liver injury. LGG or a combination of LGG and inosine were administrated orally to explore a new therapeutic method for alcohol-induced liver disease and to investigate the underlying mechanisms. Liver damage was evaluated by transaminases and pathological changes. Tight junction proteins, composition of the gut microbiome, cytokines, lipopolysaccharides (LPS), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), F4/80+ macrophages, as well as p38, Jun N-terminal kinase (JNK), were determined by qRT-PCR, RNAseq, ELISA, IHC and western blot. Regulatory T (Treg) cells were characterized by positive staining of CD4, CD25 and Foxp3 using flow cytometry. IFN-γ-producing CD4+ T (Th1) cells were examined by intracellular cytokine staining. RESULTS: Alcohol consumption induced elevated liver enzymes, steatosis and inflammation, while LGG combined with inosine treatment was more significant to ameliorate these symptoms compared with LGG alone. When LGG combined with inosine were administered to ALD mice, intestinal microecology significantly improved reflected by intestinal villi and tight junction proteins recovery and the restoration of intestinal flora. Combined therapy inhibited phosphorylation of p38 and JNK to alleviate hepatic inflammation. Moreover, flow cytometry analysis showed that long-term excessive alcohol consumption reduced Tregs population while increased Th1 population, which was restored by a combination of LGG and inosine treatment. CONCLUSIONS: The findings from the study indicate that the combined LGG and inosine treatment ameliorates ALD by improving the gut ecosystem, intestinal barrier function, immune homeostasis and liver injury.

Dynamic Behaviors of Newly Deposited Atmospheric Heavy Metals in the Soil-Pak Choi System.

Dynamic behaviors of the newly deposited atmospheric heavy metals in the soil-pak choi (Brassica chinensis L.) system are investigated by a fully factorial atmospheric exposure experiment using soils exposed to 0.5-year and 1.5-year atmospheric depositions. The results showed approximately 17-87%, 19-64%, and 43-84% of the Cu, Cd, and Pb in pak choi edible parts were contributed from the new depositions, respectively. For the newly deposited metals, foliar uptake was the key pathway of shoot bioaccumulation rather than from root uptake of the deposited metals in soils, resulting in no significant soil contribution differences between pak chois growing in 0.5-year and 1.5-year exposed soils. Indeed, highly bioavailable metals in atmospheric deposition significantly increased the soil plant-bioavailable Cu, Cd, and Pb fractions; however, soil aging resulted in similar percentages of the plant-bioavailable fractions in 0.5-year and 1.5-year exposed soils, which indicated the bioavailability of metals deposited into soils rapidly decreased with aging. The soil aging process of the deposited metals was well fitted with the first-order exponential decay model, and soil organic matter and clay were the major driving factors. Our findings highlight high plant bioaccumulation rates and the rapid soil aging process of newly deposited metals during the plant growth period.

Detection of Trace Explosives Using a Novel Sample Introduction and Ionization Method.

A novel sample introduction and ionization method for trace explosives detection is proposed and investigated herein, taking into consideration real-world application requirements. A thermal desorption sampling method and dielectric barrier discharge ionization (DBDI) source, with air as the discharge gas, were developed. The counter flow method was adopted firstly into the DBDI source to remove the interference of ozone and other reactive nitrogen oxides. A separated reaction region with an ion guiding electric field was developed for ionization of the sample molecules. Coupled with a homemade miniature digital linear ion trap mass spectrometer, this compact and robust design, with further optimization, has the advantages of soft ionization, a low detection limit, is free of reagent and consumable gas, and is an easy sample introduction. A range of common nitro-based explosives including TNT, 2,4-DNT, NG, RDX, PETN, and HMX has been studied. A linear response in the range of two orders of magnitude with a limit of detection (LOD) of 0.01 ng for TNT has been demonstrated. Application to the detection of real explosives and simulated mixed samples has also been explored. The work paves the path to developing next generation mass spectrometry (MS) based explosive trace detectors (ETDs).

Portable Digital Linear Ion Trap Mass Spectrometer Based on Separate-Region Corona Discharge Ionization Source for On-Site Rapid Detection of Illegal Drugs.

As narcotic control has become worse in the past decade and the death toll of drug abuse hits a record high, there is an increasing demand for on-site rapid detection of illegal drugs. This work developed a portable digital linear ion trap mass spectrometer based on separate-region corona discharge ionization source to meet this need. A separate design of discharge and reaction regions was adopted with filter air as both carrier gas for the analyte and protection of the corona discharge needle. The linear ion trap was driven by a digital waveform with a low voltage (±100 V) to cover a mass range of 50-500 Da with a unit resolution at a scan rate of 10,000 Da/s. Eighteen representative drugs were analyzed, demonstrating excellent qualitative analysis capability. Tandem mass spectrometry (MS/MS) was also performed by ion isolation and collision-induced dissociation (CID) with air as a buffer gas. With cocaine as an example, over two orders of magnitude dynamic range and 10 pg of detection limit were achieved. A single analysis time of less than 10 s was obtained by comparing the information of characteristic ions and product ions with the built-in database. Analysis of a real-world sample further validated the feasibility of the instrument, with the results benchmarked by GC-MS. The developed system has powerful analytical capability without using consumables including solvent and inert gas, meeting the requirements of on-site rapid detection applications.

Carbon monoxide enhances calcium transients and glucose-stimulated insulin secretion from pancreatic ß-cells by activating Phospholipase C signal pathway in diabetic mice.

In early stage of diabetes, insulin secretion from pancreatic ß-cells is increased to deal with the elevated blood glucose. Previous studies have reported that islet-produced carbon monoxide (CO) is associated with increased glucose-stimulated insulin secretion from ß-cells. However, this compensatory mechanism by which CO may act to enhance ß-cell function remain unclear. In this study, we revealed that CO promoted intracellular calcium ([Ca2+]i) elevation and glucose-stimulated insulin secretion (GSIS) from pancreatic ß-cells in leptin receptor deficient db/db mice but not in C57 mice. The stimulatory effects of CO on ß-cell function in db/db mice was blocked by inhibition of Phospholipase C (PLC) signaling pathway. We further demonstrated that CO triggered [Ca2+]i transients and enhanced GSIS in C57 islets when ß-cells overexpressed with PLCγ1 and PLCδ1, but not PLCß1. On the other hand, reducing PLCγ1 and PLCδ1 expressions in db/db islets dramatically attenuated the stimulatory effects of CO on ß-cell function, whereas interfering PLCß1 expression had no effects on CO-induced ß-cell function enhancement. Our findings showing that CO elevated [Ca2+]i and enhanced GSIS by activating PLC signaling through PLCγ1 and PLCδ1 isoforms in db/db pancreatic ß-cells may suggest an important mechanism by which CO promotes ß-cell function to prevent hyperglycemia. Our study may also provide new insights into the therapy for type II diabetes and offer a potential target for therapeutic applications of CO.

Clinical characteristics of re-hospitalized COVID-19 patients with recurrent positive SARS-CoV-2 RNA: a retrospective study.

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

Controllable high-performance memristors based on 2D Fe2GeTe3oxide for biological synapse imitation.

Memristors are an important component of the next-generation artificial neural network, high computing systems, etc. In the past, two-dimensional materials based memristors have achieved a high performance and low power consumption, though one at the cost of the other. Furthermore, their performance can not be modulated frequently once their structures are fixed, which remains the bottleneck in the development. Herein, a series of forming free memristors are fabricated with the same Cu/Fe3GeTe2oxide/Fe3GeTe2/Al structure, yet the On/Off ratio and set voltage is modulated continuously by varying the oxidation time during fabrication. With an optimal oxidation time, a large On/Off ratio (1.58 × 103) and low set voltage (0.74 V) is achieved in a single device. The formation and rapture of Al conductive filaments are found to be responsible for the memristors, and the filaments density and the cross-section area increase with the increase of current compliance, which achieves a higher On/Off ratio. The memristor can imitate basic biological synaptic functions using voltage pulses, demonstrating the potential for low-power consuming neuromorphic computing applications.