Study on the alleviative effect of Lactobacillus plantarum on Eimeria falciformis infection.

Coccidia of the genus Eimeria are specialized intracellular parasitic protozoa that cause severe coccidiosis when they infect their hosts. Animals infected with Eimeria develop clinical symptoms, such as anorexia, diarrhea, and hematochezia, which can even cause death. Although the current preferred regimen for the treatment of coccidiosis is antibiotics, this treatment strategy is limited by the ban on antibiotics and the growing problem of drug resistance. Therefore, the exploration of alternative methods for controlling coccidiosis has attracted much attention. Lactobacillus plantarum has been shown to have many beneficial effects. In this study, L. plantarum M2 was used as a research object to investigate the effect of L. plantarum on intestinal inflammation induced by infection with Eimeria falciformis in mice by detecting indicators, such as oocyst output, serum cytokines, and the intestinal microbiota. Compared with that in the infection group, the percent weight loss of the mice that were administered with L. plantarum M2 was significantly reduced (P < 0.05). Supplemented L. plantarum M2 and probiotics combined with diclazuril can reduce the total oocyst output significantly (P < 0.05, P < 0.001). L. plantarum M2 had outstanding performance in maintaining intestinal barrier function, and the levels of the mucin MUC1 and the tight junction protein E-cadherin were significantly elevated (P < 0.01, P < 0.05). Studies have shown that probiotic supplementation can alleviate adverse reactions after infection and significantly improve intestinal barrier function. In addition, probiotics combined with diclazuril could optimize the partial efficacy of diclazuril, which not only enhanced the effect of antibiotics but also alleviated their adverse effects. This study expands the application of probiotics, provides new ideas for alternative strategies for coccidia control, and suggests a basis for related research on lactobacilli antagonizing intracellular pathogen infection.IMPORTANCECoccidia of the genus Eimeria are specialized intracellular parasitic protozoa, and the current preferred regimen for the treatment of coccidiosis is antibiotics. However, due to antibiotic bans and drug resistance, the exploration of alternative methods for controlling coccidiosis has attracted much attention. In this work, we focused on Lactobacillus plantarum M2 and found that probiotic supplementation can alleviate adverse reactions after infection and improve intestinal barrier function. This study proposes the possibility of using lactic acid bacteria to control coccidiosis, and its potential mechanism needs further exploration.

Prediction of suitable regions of wild tomato provides insights on domesticated tomato cultivation in China.

Climate change is one of the biggest challenges to the world at present. Tomato is also suffered from devastating yield loss due to climate change. The domesticated tomato (Solanum lycopersicum) is presumed to be originated from the wild tomato (S. pimpinellifolium). In this study, we compared the climate data of S. pimpinellifollium with the domesticated tomato, predicted the suitable regions of S. pimpinellifollium in China using MaxEnt model and assessed their tolerance to drought stress. We found that the predicted suitable regions of wild tomato are highly consistent with the current cultivated regions of domesticated tomato, suggesting that the habitat demand of domesticated tomato descended largely from its ancestor, hence the habitat information of wild tomato could provide a reference for tomato cultivation. We further predicted suitable regions of wild tomato in the future in China. Finally, we found that while average drought tolerance between wild and domesticated tomato accessions shows no difference, tolerance levels among wild tomato accessions exhibit higher variation, which could be used for future breeding to improve drought resistance. To summarize, our study shows that suitable regions of wild tomato provide insights into domesticated tomato cultivation in China.

Constitutive activation of ABA receptors in Arabidopsis reveals unique regulatory circuitries.

Abscisic acid (ABA) is best known for regulating the responses to abiotic stressors. Thus, applications of ABA signaling pathways are considered promising targets for securing yield under stress. ABA levels rise in response to abiotic stress, mounting physiological and metabolic responses that promote plant survival under unfavorable conditions. ABA elicits its effects by binding to a family of soluble receptors found in monomeric and dimeric states, differing in their affinity to ABA and co-receptors. However, the in vivo significance of the biochemical differences between these receptors remains unclear. We took a gain-of-function approach to study receptor-specific functionality. First, we introduced activating mutations that enforce active ABA-bound receptor conformation. We then transformed Arabidopsis ABA-deficient mutants with the constitutive receptors and monitored suppression of the ABA deficiency phenotype. Our findings suggest that PYL4 and PYL5, monomeric ABA receptors, have differential activity in regulating transpiration and transcription of ABA biosynthesis and stress response genes. Through genetic and metabolic data, we demonstrate that PYR1, but not PYL5, is sufficient to activate the ABA positive feedback mechanism. We propose that ABA signaling - from perception to response - flows differently when triggered by different PYLs, due to tissue and transcription barriers, thus resulting in distinct circuitries.

Nitrogen-mediated volatilisation of defensive metabolites in tomato confers resistance to herbivores.

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.

Cations Induced Fluorescence Enhancement in Keggin-Al13 for Quantitative Detection.

The Keggin-Al13 hydroxide clusters serve as pivotal models for elucidating molecular pathways in geochemical reactions. In this study, we presented a strategy aiming at the quantitative detection of ε-Al13 Keggin clusters using photoluminescent spectra. Specifically, we manipulate the electronic structure of ε-Al13 by introducing Na ions onto the ε-Al13 surface, encapsulated within a Na-O3 motif. The Na-ion-modified ε-Al13 (Na-ε-Al13) cluster demonstrates incredible photoluminescent qualities, with fluorescence excitation and emission peaks centered at 365 and 436 nm, respectively. In addition, the fluorescence intensities display a linear dependence on the concentrations of Na-ε-Al13, with a detection limit of 15.4 µM. This correlation facilitates the quantitative and precise determination of Na-ε-Al13 concentrations via fluorescence. Both experimental characterizations and theoretical calculations underscore the importance of decorated Na ions in regulating the electronic structure of the ε-Al13 cluster. Lastly, the influence of external anions/cations on the photoluminescent properties of ε-Al13 primarily mirrors modifications to the nonradiative decay process, which is regulated via electrostatic interactions. This work demonstrates an effective strategy for quantitative detection of the ε-Al13 Keggin clusters through photoluminescent spectra.

Abnormal Out-of-Plane Vibrational Raman Mode in Electrochemically Intercalated Multilayer MoS2.

Raman spectroscopy is a powerful technique to probe structural and doping behaviors of two-dimensional (2D) materials. In MoS2, the always coexisting in-plane (E2g1) and out-of-plane (A1g) vibrational modes are used as reliable fingerprints to distinguish the number of layers, strains, and doping levels. In this work, however, we report an abnormal Raman behavior, i.e., the absence of the A1g mode in cetyltrimethylammonium bromide (CTAB)-intercalated MoS2 superlattice. This unusual behavior is quite different from the softening of the A1g mode induced by surface engineering or electric-field gating. Interestingly, under a strong laser illumination, heating, or mechanical indentation, an A1g peak gradually appears, accompanied by the migration of intercalated CTA+ cations. The abnormal Raman behavior is mainly attributed to the constraint of the out-of-plane vibration due to intercalations and resulting severe electron doping. Our work renews the understanding of Raman spectra of 2D semiconducting materials and sheds light on developing next-generation devices with tunable structures.

Treatment of Coking Wastewater Using Hydrodynamic Cavitation Coupled with Fenton Oxidation Process.

Effective and economical processes for the advanced treatment of coking wastewater were urgently needed to reduce the persistent organic pollutants of external drainage. In the present work, we investigated the degradation of organic pollutants in coking wastewater through IHC/FO (imping stream hydrodynamic cavitation (IHC) coupled with the Fenton oxidation (FO) process) and IHC alone for their feasibility in the advanced treatment of coking wastewater. To select the optimum parameters, attention was paid to the effects of main operation conditions including inlet fluid pressure, medium temperature, initial pH, reaction time, and initial Fe(II) and initial H2O2 concentrations. The results showed that the effects of conditions that need energy to be maintained (such as initial pH and inlet pressure) on the organic pollutant removal efficiency through IHC/FO were less pronounced than those through IHC alone. Moreover, the application of IHC/FO could remove more organic pollutants from coking wastewater than IHC even at an energy-efficient condition. For example, the highest COD removal efficiency of 12.5% was achieved in the IHC treatment at 0.4 MPa, pH 3, and 60 min for the reaction time. In the case of IHC/FO, the maximum COD removal of 33.2% was obtained at pH 7, 0.1 MPa, 12 mmol/L H2O2, and 3 mmol/L Fe2+ after reacting for 15 min. The ultraviolet and visible spectrophotometry (UV-Vis) absorption spectra and gas chromatography and mass spectrometry (GC-MS) analysis further revealed that the kinds and amounts of pollutants (especially those that had benzenes) remaining in water treated through IHC/FO were much fewer and smaller than in water treated through IHC alone. The better performances of IHC/FO than IHC alone were likely related to the more hydroxyl radicals produced through IHC/FO. Taken together, our findings indicate that IHC/FO has great application potential in the advanced treatment of coking wastewater.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Diagnostic Performance of 60 MHz High-Definition Intravascular Ultrasound versus Fourier Domain Optical Coherence Tomography for Identifying Plaque Rupture, Plaque Erosion, and Thrombosis in a Rabbit Model.

Background: Most acute coronary syndromes occur due to coronary thrombosis caused by plaque rupture (PR) and plaque erosion (PE). Precise in vivo differentiation between PR and PE is challenging for intravascular imaging. This study is the first to determine the diagnostic performance of the novel 60 MHz high-definition intravascular ultrasound (HD-IVUS) for differentiating atherosclerotic plaque morphology influenced by local hemodynamic flow in rabbits. This study evaluated the diagnostic performance of 60 MHz HD-IVUS in identifying thrombosis in rabbits. Methods: We established 60 rabbit models of atherosclerosis with left common carotid artery (LCCA) stenosis and 30 FeCl 3 -induced LCCA thrombosis. Intravascular imaging was assessed with 60 MHz HD-IVUS and fourier-domain optical coherence tomography (FD-OCT). The present study investigated the diagnostic accuracy of 60 MHz HD-IVUS for PR and PE, as well as thrombosis, using OCT-diagnosis as a standard reference. Results: 60 MHz HD-IVUS for identifying atherosclerotic plaque morphology using plaque cavity and minor intimal irregularities showed high sensitivity and specificity; 92.0 and 90.0% for identifying OCT-defined PR, and 80.0 and 70.0% for OCT-defined PE, respectively. In a rabbit thrombus model, 60 MHz HD-IVUS showed high sensitivity (88.0%) and specificity (80.0%) in identifying OCT-defined thrombosis. Conclusions: 60 MHz HD-IVUS can accurately identify PR and thrombosis. Further studies should confirm the clinical value of this novel technique in PE diagnosis.

Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: a pilot study.

BACKGROUND: Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine. METHODS: We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic or chronic migraine recruited chronologically from a randomized clinical trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI). Continuous variables were presented as means ± standard deviationas well as medians, and comparisons between patients and healthy volunteers were performed with non-parametric Wilcoxon signed rank tests. Statistical analysis was performed using Stata (StataCorp. 2019. Stata Statistical Software). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019). RESULTS: We observed that migraineurs had a significantly lower percentage of non-classical monocytes (CD14+CD16++) in blood circulation, compared to the control group. In addition, Migraineurs also showed a significantly lower percentage of blood CD3+CD4+ helper T cells and CD4+CD25+ regulatory T cells, compared to controls. Differences in leukocyte surface markers between chronic migraine patients and their matched controls were more prominent than those between episodic migraine patients and their matched controls. CONCLUSIONS: Our results suggest that migraine is associated with dysregulated peripheral immune homeostasis and that inflammation and autoimmunity may play a role in its pathophysiology.

A ligand-independent origin of abscisic acid perception.

Land plants are considered monophyletic, descending from a single successful colonization of land by an aquatic algal ancestor. The ability to survive dehydration to the point of desiccation is a key adaptive trait enabling terrestrialization. In extant land plants, desiccation tolerance depends on the action of the hormone abscisic acid (ABA) that acts through a receptor-signal transduction pathway comprising a PYRABACTIN RESISTANCE 1-like (PYL)-PROTEIN PHOSPHATASE 2C (PP2C)-SNF1-RELATED PROTEIN KINASE 2 (SnRK2) module. Early-diverging aeroterrestrial algae mount a dehydration response that is similar to that of land plants, but that does not depend on ABA: Although ABA synthesis is widespread among algal species, ABA-dependent responses are not detected, and algae lack an ABA-binding PYL homolog. This raises the key question of how ABA signaling arose in the earliest land plants. Here, we systematically characterized ABA receptor-like proteins from major land plant lineages, including a protein found in the algal sister lineage of land plants. We found that the algal PYL-homolog encoded by Zygnema circumcarinatum has basal, ligand-independent activity of PP2C repression, suggesting this to be an ancestral function. Similarly, a liverwort receptor possesses basal activity, but it is further activated by ABA. We propose that co-option of ABA to control a preexisting PP2C-SnRK2-dependent desiccation-tolerance pathway enabled transition from an all-or-nothing survival strategy to a hormone-modulated, competitive strategy by enabling continued growth of anatomically diversifying vascular plants in dehydrative conditions, enabling them to exploit their new environment more efficiently.

Monolayer MoS2 Synaptic Transistors for High-Temperature Neuromorphic Applications.

As essential units in an artificial neural network (ANN), artificial synapses have to adapt to various environments. In particular, the development of synaptic transistors that can work above 125 °C is desirable. However, it is challenging due to the failure of materials or mechanisms at high temperatures. Here, we report a synaptic transistor working at hundreds of degrees Celsius. It employs monolayer MoS2 as the channel and Na+-diffused SiO2 as the ionic gate medium. A large on/off ratio of 106 can be achieved at 350 °C, 5 orders of magnitude higher than that of a normal MoS2 transistor in the same range of gate voltage. The short-term plasticity has a synaptic transistor function as an excellent low-pass dynamic filter. Long-term potentiation/depression and spike-timing-dependent plasticity are demonstrated at 150 °C. An ANN can be simulated, with the recognition accuracy reaching 90%. Our work provides promising strategies for high-temperature neuromorphic applications.

Dissecting the Molecular Regulation of Natural Variation in Growth and Senescence of Two Eutrema salsugineum Ecotypes.

Salt cress (Eutrema salsugineum, aka Thellungiella salsuginea) is an extremophile and a close relative of Arabidopsis thaliana. To understand the mechanism of selection of complex traits under natural variation, we analyzed the physiological and proteomic differences between Shandong (SD) and Xinjiang (XJ) ecotypes. The SD ecotype has dark green leaves, short and flat leaves, and more conspicuous taproots, and the XJ ecotype had greater biomass and showed clear signs of senescence or leaf shedding with age. After 2-DE separation and ESI-MS/MS identification, between 25 and 28 differentially expressed protein spots were identified in shoots and roots, respectively. The proteins identified in shoots are mainly involved in cellular metabolic processes, stress responses, responses to abiotic stimuli, and aging responses, while those identified in roots are mainly involved in small-molecule metabolic processes, oxidation-reduction processes, and responses to abiotic stimuli. Our data revealed the evolutionary differences at the protein level between these two ecotypes. Namely, in the evolution of salt tolerance, the SD ecotype highly expressed some stress-related proteins to structurally adapt to the high salt environment in the Yellow River Delta, whereas the XJ ecotype utilizes the specialized energy metabolism to support this evolution of the short-lived xerophytes in the Xinjiang region.

Tomato protein phosphatase 2C influences the onset of fruit ripening and fruit glossiness.

Abscisic acid (ABA) plays a vital role in coordinating physiological processes during fresh fruit ripening. Binding of ABA to receptors facilitates the interaction and inhibition of type 2C phosphatase (PP2C) co-receptors. However, the exact mechanism of PP2C during fruit ripening is unclear. In this study, we determined the role of the tomato ABA co-receptor type 2C phosphatase SlPP2C3, a negative regulator of ABA signaling and fruit ripening. SlPP2C3 selectively interacted with monomeric ABA receptors and SlSnRK2.8 kinase in both yeast and tobacco epidermal cells. Expression of SlPP2C3 was ABA-inducible, which was negatively correlated with fruit ripening. Tomato plants with suppressed SlPP2C3 expression exhibited enhanced sensitivity to ABA, while plants overexpressing SlPP2C3 were less sensitive to ABA. Importantly, lack of SlPP2C3 expression accelerated the onset of fruit ripening and affected fruit glossiness by altering the outer epidermis structure. There was a significant difference in the expression of cuticle-related genes in the pericarp between wild-type and SlPP2C3-suppressed lines based on RNA sequencing (RNA-seq) analysis. Taken together, our findings demonstrate that SlPP2C3 plays an important role in the regulation of fruit ripening and fruit glossiness in tomato.

Clozapine affects the pharmacokinetics of risperidone and inhibits its metabolism and P-glycoprotein-mediated transport in vivo and in vitro: A safety attention to antipsychotic polypharmacy with clozapine and risperidone.

Antipsychotic polypharmacy (APP), as one maintenance treatment strategy in patients with schizophrenia, has gained popularity in real-world clinical settings. Risperidone (RIS) and clozapine (CLZ) are the most commonly prescribed second-generation antipsychotics, and they are often used in combination as APP. In this study, the pharmacokinetics of RIS and CLZ in rats were examined after co-administration to explore the reliability and rationality of co-medication with RIS and CLZ. In addition, the effects of CLZ on RIS metabolism and transport in vitro were investigated. The results illustrated that in the 7-day continuous administration test in rats, when co-administered with CLZ, the area under curve and peak concentrations of RIS were increased by 2.2- and 3.1-fold at the first dose, respectively, increased by 3.4- and 6.2-fold at the last dose, respectively. The metabolite-to-parent ratio of RIS was approximately 22% and 33% lower than those of RIS alone group at the first and last doses, respectively. Moreover, CLZ significantly increased RIS concentrations in the brain (3.0-4.8 folds) and cerebrospinal fluid (2.1-3.5 folds) in rats, which was slightly lower than the impact of verapamil on RIS after co-medication. Experiments in vitro indicated that CLZ competitively inhibited the conversion of RIS to 9-hydroxy-RIS with the inhibition constants of 1.36 and 3.0 µM in rat and human liver microsomes, respectively. Furthermore, the efflux ratio of RIS in Caco-2 monolayers was significantly reduced by CLZ at 1 µM. Hence, CLZ may affect the exposure of RIS by inhibiting its metabolism and P-glycoprotein-mediated transport. These findings highlighted that APP with RIS and CLZ might increase the plasma concentrations of RIS and 9-hydroxy-RIS beyond the safety ranges and cause toxic side effects.

Pharmacokinetics of S-epacadostat, an indoleamine 2,3-dioxygenase 1 inhibitor, in dog plasma and identification of its metabolites in vivo and in vitro.

S-epacadostat (S-EPA) is an efficient and selective small-molecule inhibitor of indoleamine 2,3-dioxygenase 1. It is an EPA analog with a sulfur atom instead of a nitrogen atom at the furazan C3 position. This study documents the pharmacokinetics of S-EPA in dogs and its metabolic pathway. After an oral administration of 15 mg/kg of S-EPA in dogs, the time to peak concentration was 0.80 h, the mean elimination half-life was 7.3 h, and the absolute bioavailability was 55.8%. Furthermore, we identified S-EPA metabolites in dog plasma and dog liver microsomes by UPLC-Q Exactive Orbitrap HRMS. In dog plasma, we found five metabolites, which came from glucuronidation (M1 and M2), deoxygenation (the amidine M4), glucuronidation of M4 (M3), and desulfonamidation and oxidation of M4 (the carboxylic acid M5). In dog liver microsomes, we identified three major metabolites, namely, the glucuronide conjugate (M6), a mono-oxidation product (M7), and a desulfonamidation and oxidation product (M8). Gut microbiota may cause the differences between in vivo and in vitro oxidation metabolisms. Contrary to EPA, S-EPA did not undergo dealkylation, suggesting that substituting the nitrogen with sulfur affects the metabolism of the adjacent alkyl side chain.

Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aß production and clearance and gut microbiota dysbiosis.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta-protein (Aß) plaques, which are the hallmark of AD, are formed from the imbalance of Aß production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple-pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi-target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aß deposition by reducing the formation of Aß and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aß production and clearance and gut microbiota dysbiosis.

Comparative pharmacokinetics of Ding-Zhi-Xiao-Wan preparation and its single herbs in rats by using a putative multiple-reaction monitoring UPLC-MS/MS method.

INTRODUCTION: The formula of Chinese medicine, Ding-Zhi-Xiao-Wan (DZXW), has the distinct feature of compatibility therapy, which is attributed to the interactions of multi-herbs. However, the quantification problem caused by the absence of pure reference standards is a bottleneck to clarify the compatibility advantages from the perspective of pharmacokinetics (PKs). OBJECTIVE: This study aimed to develop a putative multiple-reaction monitor (PMRM) strategy for exploring the comparative PKs of DZXW and its single herbs. METHODS: First, precursor ion and tandem mass spectrometry (MS/MS) chromatograms were obtained via ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight MS (UHPLC-Q-TOF-MS) under different collision energy (CE) values. Then, the two most abundance ions in the MS/MS chromatograms were chosen as product ions, and CE values were selected according to the abundance of the product ion peaks. Next, a PMRM strategy consisting of optimal MRM parameters was constructed. Finally, the established PMRM parameters were imported to UHPLC coupled with triple quadrupole MS (UHPLC-TQ-MS) for quantification. RESULTS: The strategy was exemplified by the comparative PK study of DZXW and its single herbs. This strategy could extend the PK scopes of multi-components. The quantitative results displayed substantial variations in PK parameters between DZXW and its single herbs. CONCLUSION: The PK parameters indicated that the DZXW formula could increase the exposure levels of most ingredients and reduce the maximum concentration (Cmax ) of Radix Polygala, indicating that herb compatibility could produce synergistic effects and diminish possible toxic effects. This study provides a viable orientation for the compatibility investigation of traditional Chinese medicine.

Polymeric Sulfur as a Li Ion Conductor.

The typical polymer electrolyte matrix has been limited to the chains consisting of -C-C- or -C-O-C- or -Si-O- backbone with different solvating groups for decades. In this work, the polymeric sulfur consisting of -(S-S)n- backbone with a high sulfur content (up to 90 wt % S) was reported for the first time. The flexible -(S-S)n- chains with high S atom density create an intense "solvating" environment for Li+ conduction, achieving an excellent Li+ conductivity of 1.69 × 10-3 S cm-1 at 80 °C. Benefiting from its unique thermoplasticity, a hot-rolling process was also developed for fabricating the poly-S membrane. The symmetric solid-state Li cell using the membrane showed a high cycling stability over 300 h. The work offers a novel platform for chemists to design new polymer electrolytes that are quite different with conventional carbon-based polymer electrolytes.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies as a Serologic Marker of Infection in Patients With Coronavirus Disease 2019.

BACKGROUND: Thousands of medical staff have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with hundreds of deaths reported. Such loss could be prevented if there were a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using Chinese hamster ovarian (CHO) cell-expressed full-length SARS-CoV-2 S1 protein as capturing antigen, a coronavirus disease 2019 (COVID-19)/SARS-CoV-2 S1 serology enzyme-linked immunosorbent assay (ELISA) kit was developed and validated with negative samples collected prior to the outbreak or during the outbreak and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day 1 after the onset of COVID-19 disease. The average antibody levels increased during hospitalization and 14 days after discharge. SARS-CoV-2 antibodies were detected in 28 of 276 asymptomatic medical staff and 1 of 5 nucleic acid test-negative "close contacts" of COVID-19 patients. CONCLUSIONS: With the assays developed here, we can screen medical staff, incoming patients, passengers, and people who are in close contact with the confirmed patients to identify the "innocent viral spreaders," protect the medical staff, and stop further spread of the virus.