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Brucella virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for Brucella to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type Brucella infection triggers host cell ferroptosis and what role it plays in Brucella infection. We assessed the effects of Brucella infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of Brucella infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of Brucella. The results demonstrated that Brucella M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased Brucella intracellular survival and suppressing host cell ferroptosis increased Brucella intracellular replication and egress. Collectively, Brucella may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how Brucella completes its intracellular life cycle.

ABSTRACT Brucella is a facultative intracellular pathogen that preferentially colonizes reproductive organs and utilizes erythritol as a preferred carbon source for its survival and proliferation. In this study, we identified a virulence-related DeoR-family transcriptional regulator (VdtR) and an erythronate metabolic pathway responsible for four-carbon acid sugar metabolism of D-erythronate and L-threonate in Brucella. We found that VdtR plays an important role in Brucella intracellular survival and trafficking to the endoplasmic reticulum in RAW 264.7 macrophages and in virulence in a mouse model. More importantly, we found that VdtR negatively regulates the erythronate metabolic pathway to promote extracellular proliferation of Brucella, depending on utilization of D-erythronate, an oxidative product of erythritol in the host. In a pregnant mouse model, the erythronate metabolic pathway was shown to cooperate with erythritol metabolism and play a crucial role in Brucella proliferation in the placenta, inducing placentitis and finally resulting in abortion or stillbirth. Our results demonstrate that, in addition to erythritol, erythronate is a preferred carbon source for Brucella utilization to promote its extracellular proliferation. This discovery updates the information on the preferential colonization of reproductive organs by Brucella and provides a novel insight into the Brucella-associated induction of abortion in pregnant animals. IMPORTANCE Brucella is an intracellular parasitic bacterium causing zoonosis, which is distributed worldwide and mainly characterized by reproductive disorders. Erythritol is found in allantoic fluid, chorion, and placenta of aborted animals, preferentially utilized by Brucella to cause infertility and abortion. However, the erythritol metabolism-defected mutant was unable to function as a vaccine strain due to its residual virulence. Here, we found that erythronate, an oxidative product of erythritol in the host, was also preferentially utilized by Brucella relying on the function of a deoxyribonucleoside regulator-family transcriptional regulator VdtR. Erythronate utilization activates VdtR regulation of the erythronate metabolic pathway to promote Brucella extracellular proliferation, inducing placentitis/abortion in mice. Double mutations on Brucella erythritol and D-erythronate metabolisms significantly reduced bacterial virulence. This study revealed a novel mechanism of Brucella infection-induced abortion, thus providing a new clue for the study of safer Brucella attenuated vaccines.

Background Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.Aims The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide.Methods The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel.Results Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme.Conclusions This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.

Context Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.Objective To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP.Materials and methods An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis.Results Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold).Discussion and conclusions This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

AimPreviously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy.MethodsThirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales.ResultsCompared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD.ConclusionThe results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.

Background: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. Methods: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1’s function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. Results: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect. Conclusions: PAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.

Abstract In this article, we review the recent progress of the scanning tunneling microscopy studies of 1T-TaS2 and 1T-TaSe2 for bulk single crystals and molecular beam epitaxy monolayer films. We focus on how to understand the Mott insulating state in the whole set of materials, even when the stacking order takes effect. Based on this understanding, we discuss tuning the Mott insulator to a metallic state with different techniques, with Mott physics information revealed from the tuning process. The Kondo physics and quantum spin liquid state of 1T-TaS2 and 1T-TaSe2 are further discussed. This good platform of strong correlation must bring more intriguing phenomenon and physics in the future.

Abstract In this work we aim to gain qualitative insight on the far-from-equilibrium behavior of the gluon plasma produced in the early stages of a heavy-ion collision. It was recently discovered [1] that the distribution functions of quarks and gluons in QCD effective kinetic theory (EKT) exhibit self-similar “scaling” evolution with time-dependent scaling exponents long before those exponents reach their pre-hydrodynamic fixed-point values. In this work we shed light on the origin of this time-dependent scaling phenomenon in the small-angle approximation to the Boltzmann equation. We first solve the Boltzmann equation numerically and find that time-dependent scaling is a feature of this kinetic theory, and that it captures key qualitative features of the scaling of hard gluons in QCD EKT. We then proceed to study scaling analytically and semi-analytically in this equation. We find that an appropriate momentum rescaling allows the scaling distribution to be identified as the instantaneous ground state of the operator describing the evolution of the distribution function, and the approach to the scaling function is described by the decay of the excited states. That is to say, there is a frame in which the system evolves adiabatically. Furthermore, from the conditions for adiabaticity we can derive evolution equations for the time-dependent scaling exponents. In addition to the known free-streaming and BMSS fixed points, we identify a new “dilute” fixed point when the number density becomes small before hydrodynamization. Corrections to the fixed point exponents in the small-angle approximation agree quantitatively with those found previously in QCD EKT and arise from the evolution of the ratio between hard and soft scales.

There are many species of terrestrial Mollusca with rapid reproduction rates, a wide distribution range, and a large population. They are not only an important wildlife resource but also an important component of biodiversity. Previously, basic research has been conducted on the species diversity and distribution of terrestrial Mollusca in some nature reserves in Guizhou and Yunnan. The existing sample data of terrestrial Mollusca in Guizhou and survey results from Guiyang, Libo, and Xishui from July 2019 to December 2020 listed 316 species and subspecies (including 13 undefined species) belonging to two subclasses, four orders, 20 families, and 76 genera in Guizhou Province. From the perspective of species composition, the dominant family is Cyclophoridae, with 16 genera and 71 species; the second most dominant family is Bradybaenidae, with 15 genera and 61 species, followed by Helicinidae and Cochlicopidae with one genera and one species. The dominant species are Kaliella cavicola, Bradybaena similaris, Diplommatina herziana, Diplommatina consularis, Chamalycaeus nanus, and Plectotropis pseudopatula. From the perspective of geographical distribution, terrestrial Mollusca are the most abundant in the central region of Guizhou, with 17 families, 54 genera, and 170 species. The areas with the second greatest abundance of terrestrial Mollusca are the sub-subtropical humid areas in southern Guizhou and the sub-subtropical areas in southwestern Guizhou, with 18 families, 56 genera, and 152 species and 17 families, 57 genera, and 150 species, respectively. There are only 10 families, 18 genera, and 27 species in the eastern area of Guizhou. Similarity analysis of species in different regions of Guizhou Province showed that the species composition of terrestrial Mollusca in the southern area, northern area, and southwestern area of Guizhou is similar, whereas the species composition of terrestrial Mollusca in the eastern area of Guizhou is markedly different from that of other regions. This paper discusses the species and distribution pattern of terrestrial Mollusca in Guizhou Province and their resource characteristics to provide a scientific basis for the protection and rational utilization of terrestrial Mollusca resources and to further enrich the research data of terrestrial Mollusca in China.

Abstract Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global disruption of human health and activity. Being able to trace the early outbreak of SARS-CoV-2 within a locality can inform public health measures and provide insights to contain or prevent viral transmission. Investigation of the transmission history requires efficient sequencing methods and analytic strategies, which can be generally useful in the study of viral outbreaks. Methods The County of Los Angeles (hereafter, LA County) sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history, we carried out surveillance viral genome sequencing to determine 142 viral genomes from unique patients seeking care at the University of California, Los Angeles (UCLA) Health System. 86 of these genomes were from samples collected before April 19, 2020. Results We found that the early outbreak in LA County, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a USA-specific strain, B.1.43, which was found predominantly in California and Washington State. While samples from LA County carried the ancestral B.1.43 genome, viral genomes from neighboring counties in California and from counties in Washington State carried additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but might have been undermined by the many introductions of SARS-CoV-2 into the region. Conclusion Our work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the USA to have coordinated inter-state responses to the pandemic.

Abstract The non-Gaussian fluctuations of baryon density are sensitive to the presence of the conjectured QCD critical point. Their observational consequences are crucial for the ongoing experimental search for this critical point through the beam energy scan program at Relativistic Heavy Ion Collider (RHIC). In the expanding fireball created in a heavy-ion collision, critical fluctuations would inescapably fall out of equilibrium and require a systematic description within a dynamical framework. In this paper, we employ newly developed effective field theory (EFT) for fluctuating hydrodynamics to study the real-time critical non-Gaussian fluctuations of a conserved charge density. In particular, we derive the evolution equations for multi-point correlators of density fluctuations and obtain the closed-form solutions with arbitrary initial conditions that can readily be implemented in realistic simulations for heavy-ion collisions. We find that non-linear interactions among noise fields, which are missing in traditional stochastic hydrodynamics, could potentially contribute to the quartic (fourth-order) fluctuations in the scaling regime even at tree level in off-equilibrium situations.

The necessity for precise prediction of penetration depth in the context of electron beam welding (EBW) cannot be overstated. Traditional statistical methodologies, including regression analysis and neural networks, often necessitate a considerable investment of both time and financial resources to produce results that meet acceptable standards. To address these challenges, this study introduces a novel approach for predicting EBW penetration depth that synergistically combines computational fluid dynamics (CFD) modelling with artificial neural networks (ANN). The CFD modelling technique was proven to be highly effective, yielding predictions with an average absolute percentage deviation of around 8%. This level of accuracy is consistent across a linear electron beam (EB) power range spanning from 86 J/mm to 324 J/mm. One of the most compelling advantages of this integrated approach is its efficiency. By leveraging the capabilities of CFD and ANN, the need for extensive and costly preliminary testing is effectively eliminated, thereby reducing both the time and financial outlay typically associated with such predictive modelling. Furthermore, the versatility of this approach is demonstrated by its adaptability to other types of EB machines, made possible through the application of the beam characterisation method outlined in the research. With the implementation of the models introduced in this study, practitioners can exert effective control over the quality of EBW welds. This is achieved by fine-tuning key variables, including but not limited to the beam power, beam radius, and the speed of travel during the welding process.

Brucella is an intracellular parasitic bacterium that uses multiple strategies to evade the host’s defense mechanisms. However, how Brucella manipulates the host-induced oxidative stress and relevant biological processes are still poorly understood. In this study, a comparative transcriptome assay of macrophages infected with Brucella abortus S2308 and its rough mutant RB14 was performed to investigate the differentially expressed genes which might be associated with the pathogenic mechanism of Brucella. Our results showed that numerous host pro-oxidative and antioxidative stress genes were differentially expressed in macrophages infected with B. abortus S2308 and mutant RB14 at 4, 8, 24, and 48 h post-infection. Interestingly, we found that several ferroptosis-associated genes were differentially expressed during B. abortus RB14 infection. Moreover, we found that the rough mutant RB14-induced macrophage death was associated with reduced levels of host glutathione and glutathione peroxidase 4, together with increased free iron, lipid peroxidation, and ROS, all of which are important hallmarks of ferroptosis. The ferroptosis occurring during infection with RB14 was reduced by treatment with the inhibitor ferrostatin-1. However, B. abortus S2308 infection did not induce these hallmarks of ferroptosis. Taken together, our results demonstrate that ferroptosis is involved in rough B. abortus infection. Investigating how Brucella manipulates oxidative stress and ferroptosis in its host will be helpful to clarify the pathogenicity of B. abortus.

Abstract The electronic evolution of doped Mott insulators has been extensively studied for decades in search of exotic physical phases. The proposed Mott insulator 1T-TaS2 provides an intriguing platform to study the electronic evolution via doping. Here we apply scanning tunneling microscopy (STM) to study the evolution in Ti-doped 1T-TaS2 at different doping levels. The doping Ti atom locally perturbs the electronic and spin state inside the doped star of David and induces a clover-shaped orbital texture at low-doping levels (x

Purpose. Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. Methods. We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Results. Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p

Background: To systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI). Methods: One hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman’s correlation was used to examine the relationships between topological alterations and clinical variables. Results: Compared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables. Conclusions: Individual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.

A quantum eigensolver is designed under a multilayer cluster mean-field (CMF) algorithm by partitioning a quantum system into spatially-separated clusters. For each cluster, a reduced Hamiltonian is obtained after a partial average over its environment cluster. The products of eigenstates from different clusters construct a compressed Hilbert space, in which an effective Hamiltonian is diagonalized to determine certain eigenstates of the whole Hamiltonian. The CMF method is numerically verified in multispin chains and experimentally studied in a fully-connected three-spin network, both yielding an excellent prediction of their ground states.

ABSTRACT The rapid development of methicillin-resistant Staphylococcus aureus (MRSA) drug resistance and the formation of biofilms seriously challenge the clinical application of classic antibiotics. Extracts of the traditional herb Chenopodium ambrosioides L. were found to have strong antibiofilm activity against MRSA, but their mechanism of action remains poorly understood. This study was designed to investigate the antibacterial and antibiofilm activities against MRSA of flavonoids identified from C. ambrosioides L. in combination with classic antibiotics, including ceftazidime, erythromycin, levofloxacin, penicillin G, and vancomycin. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the nonvolatile chemical compositions. Reverse transcription (RT)-PCR was used to investigate potential multitargets of flavonoids based on global transcriptional responses of virulence and antibiotic resistance. A synergistic antibacterial and biofilm-inhibiting activity of the alcoholic extract of the ear of C. ambrosioides L. in combination with penicillin G was observed against MRSA, which proved to be closely related to the interaction of the main components of kaempferol rhamnosides with quercetin. In regard to the mechanism, the increased sensitivity of MRSA to penicillin G was shown to be related to the downregulation of penicillinase with SarA as a potential drug target, while the antibiofilm activity was mainly related to downregulation of various virulence factors involved in the initial and mature stages of biofilm development, with SarA and/or σB as drug targets. This study provides a theoretical basis for further exploration of the medicinal activity of kaempferol rhamnosides and quercetin and their application in combination with penicillin G against MRSA biofilm infection. IMPORTANCE In this study, the synergistic antibacterial and antibiofilm effects of the traditional herb C. ambrosioides L. and the classic antibiotic penicillin G on MRSA provide a potential strategy to deal with the rapid development of MRSA antibiotic resistance. This study also provides a theoretical basis for further optimizing the combined effect of kaempferol rhamnosides, quercetin, and penicillin G and exploring anti-MRSA biofilm infection research with SarA and σB as drug targets.

BackgroundAccumulating evidence suggests that trigeminal neuralgia (TN) causes structural and functional alterations in the brain. However, only a few studies have focused on cerebral blood flow (CBF) changes in patients with TN. This study aimed to explore whether altered cerebral perfusion patterns exist in patients with TN and investigate the relationship between abnormal regional CBF (rCBF) and clinical characteristics of TN.Materials and methodsThis study included 28 patients with TN and 30 age- and sex-matched healthy controls (HCs) who underwent perfusion functional MRI (fMRI) of the brain using pseudo-continuous arterial spin labeling (pCASL) in the resting state. The regions of significantly altered CBF in patients with TN were detected using group comparison analyses. Then, the relationships between the clinical characteristics and abnormal rCBF were further investigated.ResultsCompared to the control group, patients with TN exhibited increased rCBF, primarily in the thalamus, middle frontal gyrus (MFG), and left insula. Furthermore, the CBF values of the thalamus were negatively correlated with the pain intensity of TN and positively correlated with pain duration in patients with TN.ConclusionPrimary alterations in rCBF in patients with TN occurred in different brain regions related to pain, which are involved in cognitive-affective interaction, pain perception, and pain modulation. These results indicate that non-invasive resting cerebral perfusion imaging may contribute complementary information to further understanding the neuropathological mechanism underlying TN.

Sector-based methane emissions can be backed out from observed methane fluxes, using a Bayesian optimal estimation method. This could help with monitoring gas leaks from industry.

Abstract In this study, characteristics of charge injection under extra high electric field (above 100 kV/mm) in cross‐linked polyethylene (XLPE) were investigated by experiments of conduction current and space charge. The results show that current density from low electric field to sample breakdown corresponds to space charge limited current (SCLC) theory. More specifically, Schottky current is similar to experiment current before 100 kV/mm, while the J–E curve conforms to a modified SCLC theory after 100 kV/mm. Besides, the non‐linear coefficient of J–E curve from 100 kV/mm to extra high electric field is smaller than theoretical value, and the injection depth of space charge is restricted as the field becomes higher than 100 kV/mm, which may be caused by the negative differential mobility of charge. Driven by extra high electric field, charge collides with lattice of dielectric and scatters. As a result, mean free time of charge decreases and charge mobility is reduced with the increased field. Consequently, considering the decrease in charge mobility, a mobility‐limited charge injection equation is proposed, and the validity of the proposed equation under extra high electric field is demonstrated by space charge simulation.

Abstract We analyze the combined effects of hydrodynamic fluctuations and chiral magnetic effect (CME) for a chiral medium in the presence of a background magnetic field. Based on the recently developed non-equilibrium effective field theory, we show fluctuations give rise to a CME-related positive contribution to magnetoresistance, while the early studies without accounting for the fluctuations find a CME-related negative magnetoresistance. At zero axial relaxation rate, the fluctuations contribute to the transverse conductivity in addition to the longitudinal one.

Merozoite invasion of the erythrocytes in humans is a key step in the pathogenesis of malaria. The proteins involved in the merozoite invasion could be potential targets for the development of malaria vaccines. Novel viral-vector-based malaria vaccine regimens developed are currently under clinical trials. Vesicular stomatitis virus (VSV) is a single-stranded negative-strand RNA virus widely used as a vector for virus or cancer vaccines. Whether the VSV-based malarial vaccine is more effective than conventional vaccines based on proteins involved in parasitic invasion is still unclear. In this study, we have used the reverse genetics system to construct recombinant VSVs (rVSVs) expressing apical membrane protein 1 (AMA1), rhoptry neck protein 2 (RON2), and reticulocyte-binding protein homolog 5 (RH5), which are required for Plasmodium falciparum invasion. Our results showed that VSV-based viral vaccines significantly increased Plasmodium-specific IgG levels and lymphocyte proliferation. Also, VSV-PyAMA1 and VSV-PyRON2sp prime-boost regimens could significantly increase the levels of IL-2 and IFN-γ-producing by CD4+ and CD8+ T cells and suppress invasion in vitro. The rVSV prime-protein boost regimen significantly increase Plasmodium antigen-specific IgG levels in the serum of mice compared to the homologous rVSV prime-boost. Furthermore, the protective efficacy of rVSV prime protein boost immunization in the mice challenged with P. yoelii 17XL was better compared to traditional antigen immunization. Together, our results show that VSV vector is a novel strategy for malarial vaccine development and preventing the parasitic diseases.

Abstract Plant growth and crop harvest are impacted by both climate change and air pollution. However, their relative importance in crop yields remains elusive, especially in heavily polluted regions. Here we develop crop yield prediction models, based on a large volume of historical crop data, as well as climate and pollution records in China since 1980. A long‐term surface ozone concentration data set is developed from a machine‐learning model and various observations. An assessment of four climate and pollution factors reveals the critical role of particulate and ozone pollution in regulating interannual variations of crop yields in China. During 2010–2018, we find that the particulate pollution mitigation outweighs the negative impacts of concurrent climate change, resulting in 0.5%–1.9% net yield increases nationwide, despite of the ozone increases in the North China Plain. Looking to the future, the impacts of climate change, particularly from surface temperature increase, will dominate over pollution factors and profoundly reduce future maize and rice yields by 0.6 to 2.8% 10 yr−1 by 2050. Our findings call for attention on the threat to future global food security from the absence of pollution mitigation and the persistence of global warming.

BackgroundEmotional disturbance is an important risk factor of suicidal behaviors. To ensure speech emotion recognition (SER), a novel technique to evaluate emotional characteristics of speech, precision in labeling emotional words is a prerequisite. Currently, a list of suicide-related emotional word is absent. The aims of this study were to establish an Emotional Words List for Suicidal Risk Assessment (EWLSRA) and test the reliability and validity of the list in a suicide-related SER task.MethodsSuicide-related emotion words were nominated and discussed by 10 suicide prevention professionals. Sixty-five tape-recordings of calls to a large psychological support hotline in China were selected to test psychometric characteristics of the EWLSRA.ResultsThe results shows that the EWLSRA consists of 11 emotion words which were highly associated with suicide risk scores and suicide attempts. Results of exploratory factor analysis support one-factor model of this list. The Fleiss’ Kappa value of 0.42 indicated good inter-rater reliability of the list. In terms of criteria validities, indices of despair (Spearman ρ = 0.54, P < 0.001), sadness (ρ = 0.37, P = 0.006), helplessness (ρ = 0.45, P = 0.001), and numbness (ρ = 0.35, P = 0.009) were significantly associated with suicidal risk scores. The index of the emotional word of numbness in callers with suicide attempt during the 12-month follow-up was significantly higher than that in callers without suicide attempt during the follow-up (P = 0.049).ConclusionThis study demonstrated that the EWLSRA has adequate psychometric performance in identifying suicide-related emotional words of recording of hotline callers to a national wide suicide prevention line. This list can be useful for SER in future studies on suicide prevention.

ABSTRACT Mobile colistin resistance (mcr) genes mediated by plasmids have widely disseminated throughout the world. Recently, 10 mcr genes (mcr-1 to mcr-10) and a large number of variants have been identified in more than 60 countries. However, only a few instances of Enterobacter cloacae complex (ECC) bearing mcr-10 from animal origin have been reported globally. The aim of this study was to fill a knowledge gap in mcr-10-positive ECC of animal origin and analyze the potential transmission trend and different characteristics between human and companion animal isolates. The mcr-10 gene was identified on a self-transmissible plasmid in the human isolate and non-transmissible plasmids in other three animal strains. mcr-10 was adjacent to a XerC-type tyrosine recombinase-gene, and various insertion sequences were located on the downstream of core conservative structure xerC-mcr-10, thus indicating this region might be a candidate for insertions of mobile genetic elements and mcr-10 might be mobilized by IS-mediated mechanisms. Moreover, phylogenetic analysis found that mcr-10-positive isolates were mainly distributed in the clade of Enterobacter roggenkampii, exhibiting significant species specificity. These findings indicated that mcr-10 has emerged among Enterobacter spp. within humans and companion animals, highlighting that the importance of taking effective control measures to monitor the dissemination and evolution of mcr genes. IMPORTANCE Colistin was considered as the last-resort drug against severe clinical infections caused by multidrug-resistant Gram-negative pathogens. Mobile colistin resistance (mcr) genes and its variants carried by plasmids have been reported in diverse niches in recent years, and yet few studies reported carriage of mcr-10 in ECC strains of companion animal origin. How plasmid-borne mcr-10 transmitted in opportunistic pathogens and different characteristics of mcr-10-bearing strains isolated from humans and companion animals are not well understood. In this study, we discovered mcr-10-harboring strains in multidrug-resistant ECC isolates of companion animal origin for the first time and conducted a comprehensive analysis of the genetic environment of mcr-10 from multiple countries around the world, providing the potential basis for formulating control measures to slow down the spread of colistin resistance.

BackgroundCervical cancer, as a common gynecological disease, endangers female health. Give the lack of effective biomarkers for the diagnosis and treatment of cervical cancer, this paper aims to analyze the Gene Expression Omnibus (GEO) data sets using comprehensive bioinformatics tools, and to identify biomarkers associated with the cancer in patient samples.MethodsThe bioinformatics methods were used to extract genes related to cervical cancer from GSE39001, while the GEO2R online tool to elaborate on differentially expressed genes (DEGs) in normal and cancer samples, and to clarify related genes and functions. The results were verified by IHC, WB, CCK-8, clone formation and flow cytometry experiments.ResultsA total of 2,859 DEGs were identified in the GEO microarray dataset. We extracted genes associated with both ubiquitination and autophagy from the key modules of weighted gene co-expression network analysis (WGCNA), and the analysis showed that TRIM8 was of great significance for the diagnosis and prognosis of cervical cancer. Besides, experimental validation showed the high TRIM8 expression in cervical cancer, as well as its involvement in the proliferation of cervical cancer cells.ConclusionWe identified a biomarker (TRIM8) that may be related to cervical cancer through a series of analyses on the GEO dataset. Experimental verification confirmed the inhibition of cervical cancer cells proliferation by lowering TRIM8 expression. Therefore, TRIM8 can be adopted as a new biomarker of cervical cancer to develop new therapeutic targets.

Exosomes, as natural biomolecular carriers produced by cells, have the potential and advantage of delivering drugs to target organs or cells in vivo. The steps to improve exosomes as a drug delivery system can be divided into three steps:large-scale preparation of exosomes, loading of drugs and targeted delivery of exosomes. Based on the existing production process and technology, there is still much room for improvement. This review highlights the research progress in three aspects and proposes new technologies and innovative approaches to improve the efficiency of exosome delivery.

Two-dimensional (2D) ice I is atomic-level ice that is composed of two interlocked atomic layers saturated with hydrogen bonds. It has recently been experimentally observed, but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, a simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2D ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not destroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it can be used as an anti-3D-icing agent under low temperatures.

Background: Brucella abortus is the main causative agent for bovine brucellosis. B. abortus A19 is a widely used vaccine strain to protect cows from Brucella infection in China. However, A19 has a similar lipopolysaccharide (LPS) antigen to that of the field virulent Brucella strain, whose immunization interferes with the serodiagnosis of vaccinated and infected animals. [Aim] To develop a novel Brucella DIVA vaccine candidate. Study design and methods: The B. abortus mutant A19mut2 with the formyltransferase gene wbkC is replaced by an acetyltransferase gene wbdR from E. coli O157 using the bacterial homologous recombination technique, generating a modified O-polysaccharide that cannot induce antibodies in mice against wild-type Brucella LPS. The biological phenotypes of the A19mut2 were assessed using a growth curve analysis, agglutination tests, Western blotting, and stress resistance assays. Histopathological changes and bacterial colonization in the spleens of vaccinated mice were investigated to assess the residual virulence and protection of the A19mut2. Humoral and cellular immunity was evaluated by measuring the levels of IgG, IgG subtypes, and the release of cytokines IFN-γ and IL10 in the splenocytes of the vaccinated mice. ELISA coated with wild-type LPS can distinguish mouse antibodies induced by A19 and A19mut2 immunization. Results: The A19mut2 showed a decreased residual virulence in mice, compared to the A19 strain, but induced significant humoral and cellular immune responses, as the A19 immunization did. The protection efficacy of A19mut2 immunization against B. abortus S2308 NalR infection was similar to that of A19 immunization. Conclusion: The A19mut2 has potential as a novel DIVA vaccine candidate in the future.

This paper elucidates that the AIDS/HIV incidence rate differences exist among different population and regions, especially among the old and college students. Due to the effect of age, the AIDS incidence peak in males aged 20–35 years and 50 years old both in Chongqing and Shenzhen, and the incidence rate and increasing spread in males was higher than that of females under period effect. In the local population in Chongqing and Shenzhen, the incidence rate of males in over 40, below and in the whole age groups are predicted to increase sharply in the future six years, while in females, the incidence rates among over 40-year-old and the whole age groups were predicted to increase as well. The incidence rate among homosexually transmitted patients reaches the peak in the 20–35, the incidence rate of patients transmitted through heterosexual reaches the peak around 50-year-old. Under the effect of period, AIDS/HIV incidence rate of patients transmitted through sexual routes showed an upward trend both in Chongqing and Shenzhen. The incidence rate of patients aged between 41 and 70 years old presents with an upward trend in the future six years. The results show great differences exist in the AIDS/HIV incidence between males and females, therefore it is necessary to take specific measures respectively.

Acute cholecystitis and several gallbladder stone-related conditions, such as impacted common bile duct stones, cholangitis, and biliary pancreatitis, are common medical conditions in daily practice. An early cholecystectomy or drainage procedure with delayed cholecystectomy is the current standard of treatment based on published clinical guidelines. Cirrhosis is not only a condition of chronically impaired hepatic function but also has systemic effects in patients. In cirrhotic individuals, several predisposing factors, including changes in the bile acid composition, increased nucleation of bile, and decreased motility of the gallbladder, contribute to the formation of biliary stones and the possibility of symptomatic cholelithiasis, which is an indication for surgical treatment. In addition to these predisposing factors for cholelithiasis, systemic effects and local anatomic consequences related to cirrhosis lead to anesthesiologic risks and perioperative complications in cirrhotic patients. Therefore, the treatment of the aforementioned biliary conditions in cirrhotic patients has become a challenging issue. In this review, we focus on cholecystectomy for cirrhotic patients and summarize the surgical indications, risk stratification, surgical procedures, and surgical outcomes specific to cirrhotic patients with symptomatic cholelithiasis.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic profoundly impacts on mental health, yet it is still unclear whether COVID-19 distress makes people more vulnerable to suicidal behavior. The present study aims to examine the association between COVID-19 related psychological distress and risk for suicide attempt, and moderators of this association, among hotline callers. Methods This case-control study was conducted at the largest psychological support hotline in China. Hotline callers who sought help for psychological distress and reported whether or not they attempted suicide in the last 2 weeks (recent suicide attempt) were analyzed. The primary predictor of recent suicide attempt was the presence or absence of COVID-19 related psychological distress. Demographic variables and common risk and protective factors for suicidal behavior were also studied. Callers with COVID-19 related distress (COVID-19 callers) and those without such distress (non-COVID-19 callers) were compared on these variables. Recent suicide attempt was regressed on COVID-19 related distress and the other variables, and significant interaction terms of aforementioned predictors by COVID-19 related distress, to identify variables that moderate the association of COVID-19 related distress and recent suicide attempt. Results Among 7337 included callers, there were 1252 COVID-19 callers (17.1%) and 6085 non-COVID-19 callers (82.9%). The COVID-19 callers were less likely to report recent suicide attempt (n = 73, 5.8%) than the non-COVID-19 callers (n = 498, 8.2%, P = 0.005). The COVID-19 callers were also less likely to have high scores on depressive symptoms (22.6% vs 26.3%, P

Abstract We systematically analyze the effects of the derivatives of the hydrodynamic fields on axial Wigner function that describes the spin polarization vector in phase space. We have included all possible first-order derivative contributions that are allowed by symmetry and compute the associated transport functions at one-loop using the linear response theory. In addition to reproducing known effects due to the temperature gradient and vorticity, we have identified a number of potentially significant contributions that are overlooked previously. In particular, we find that the shear strength, the symmetric and traceless part of the flow gradient, will induce a quadrupole for spin polarization in the phase space. Our results, together with hydrodynamic gradients obtained from hydrodynamic simulations, can be employed as a basis for the interpretation of the Λ (anti-Λ) spin polarization measurement in heavy-ion collisions.

Abstract Objective To predict the trend of AIDS in specific age groups and to determine the objective population for AIDS screening, this study explored the three transmission routes and characterized each patient group using the APC model based on the whole, local, and immigrant populations in Zhejiang, China. Methods The data recruited in this paper was obtained from the national Comprehensive AIDS Prevention and Control Information System - Antiviral Therapy Management database and the Chinese Disease Prevention and Control Information System and the Statistical Yearbook of Zhejiang, China. An APC model was used to estimate the impact of age, period, and cohort on the incidence of AIDS, as well as to predict the AIDS incidence in specific age groups based on different sexes with different transmission routes. Results The AIDS incidence peaked in males aged 20–35 years; the incidence of males was higher than that of females due to the impact of period; obvious cohort effect was observed among the immigrants. In the whole and local populations, the incidences of males in all age groups and females in both the 35-year-old group and the whole age group were predicted to increase sharply in 5 years. In the immigrant population, the AIDS incidences in both sexes in all age groups were expected to increase significantly in 5 years. Under the influence of period, the incidence of AIDS via homosexual transmission in the whole population and the local population increased and remained stable after 2015. At the same time, the incidence of AIDS transmitted by homosexual and heterosexual routes in the immigrants also showed an increasing trend. Conclusions The results elucidate that there are sex differences in AIDS incidence, and the incidence of AIDS through various transmission routes in all groups is predicted to exhibit an upward trend in the 5 years to come. Effective intervention strategies should be developed and implemented by the public health departments in Zhejiang to control the epidemic of AIDS.

BackgroundPostoperative chemotherapy is a standard treatment for stage II and III gastric cancer in Asia. With regard to single-agent or doublet, the need for improvement has consistently been pointed out because of the relatively poor outcome for patients with stage III gastric cancer. Triplet has shown significant survival benefits in the perioperative setting. We conducted a randomized, multicenter, phase III study to compare triplet to doublet regimens for patients with stage III gastric cancer.MethodsThis is currently enrolling patients (n = 230) with pathologic stage III gastric cancer after D2 lymph node dissection and achieved R0 resection. Patients are randomized 1:1 and stratified by tumor stage (IIIA, IIIB, or IIIC, AJCC 8th) into POF or SOX/CAPOX/FOLFOX. S-1 and oxaliplatin (SOX): oxaliplatin 130 mg/m2 on day 1, oral S-1 80–120 mg/m2 divided by two on days 1–14 every 21 days for 8 cycles. Capecitabine and oxaliplatin (CAPOX): oxaliplatin 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1–14 every 21 days for 8 cycles. Folinic acid (or leucovorin), 5-fluorouracil and oxaliplatin (FOLFOX): oxaliplatin 85 mg/m2, levo-leucovorin 200 mg/m2, and 5-fluorouracil (5-FU) 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 h, every 14 days for 12 cycles. Three doublets were chosen by the clinicians. Paclitaxel, oxaliplatin, 5-fluorouracil, and leucovorin (POF): paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus, every 14 days for 12 cycles. The primary end point is 3-year disease-free survival (3-year-DFS). Secondary end points are overall survival (OS) and safety (any adverse event).DiscussionThe results of this study will help establish postoperative clinical evidence for patients with locally advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT0378826].

ObjectiveThis study aimed to detect the cerebral blood flow (CBF) values changes in patients with ankylosing spondylitis (AS) and to evaluate the correlation between the CBF values and the specific clinical characteristics.Materials and methodsForty-eight patients with AS (43 male and 5 female) and 42 healthy controls (HCs) (38 male and 4 female) were recruited. Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) was performed on a 3.0T magnetic resonance imaging (MRI). CBF values were obtained on the Philips post-processing workstation based on arterial spin labeling (ASL) data. The two-sample t-test was used to compare CBF differences. The correlation between CBF values and specific clinical characteristics of AS was evaluated.ResultsThe AS group showed increased CBF values in the right precentral gyrus, the left inferior frontal gyrus, and the left temporal pole compared with HCs the AS group also showed decreased CBF values in the left precuneus and the left superior occipital gyrus compared with HCs. There were no significant correlations between the CBF values and the clinical characteristics including total back pain (TBP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).ConclusionPatients with AS displayed CBF changes compared with HCs using 3D-PCASL. These results may enhance our understanding of the neural substrates of AS and provide evidence of AS-related neurological impairment.

Pyrethroids pesticides (PPs) are the widely adopted synthetic pesticides for agriculture and fishery. The frequent use of these pesticides leads to the accumulation of residues in the freshwater environments in China, subsequently affecting aquatic organisms and ecosystems. However, there are few reports on the toxicological and risk assessment of aquaculture aquatic products. In this study, the uptake, depuration kinetics and potential risk to human health and ecology of fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were assessed using tilapia. The results indicated that four PPs were readily accumulated by tilapia. The bioconcentration factors (BCF) of the PPs in plasma and muscle were between 71.3 and 2112.1 L/kg and 23.9–295.3 L/kg, respectively. The half-lives (t1/2) of muscle and plasma were 2.90–9.20 d and 2.57–8.15 d. The risks of PPs residues in the muscle of tilapia and exposed water were evaluated by hazard quotient (HQ) and risk quotient (RQ). Although PPs residues in tilapia had a low dietary risk to human health, the residues in the exposed water had a high ecological risk to fish, daphnia, and green algae. Therefore, assessing the PPs content in freshwater aquaculture and monitoring their dosages and frequencies are highly necessitated to avoid their adverse effect on the aquaculture environment.

Obstructive sleep apnea (OSA) is a serious breathing disorder, leading to myocardial infarction, high blood pressure, and stroke. Brain morphological changes have been widely reported in patients with OSA. The pathophysiological mechanisms of cerebral blood flow (CBF) changes associated with OSA are not clear. In this study, 20 patients with OSA and 36 healthy controls (HCs) were recruited, and then pseudo-continuous arterial spin labeling (pCASL) and voxel-based morphometry (VBM) methods were utilized to explore blood perfusion and morphological changes in the patients with OSA. Compared with the HC group, the OSA group showed increased CBF values in the right medial prefrontal cortex (mPFC), left precentral gyrus, and right insula and showed decreased CBF values in the right temporal pole (TP) and the right cerebellum_Crus2. Compared with the HC group, the patients with OSA showed decreased gray matter volume (GMV) in the right dorsal lateral prefrontal cortex (DLPFC), the right occipital pole, and the vermis. There were no significantly increased GMV brain regions found in patients with OSA. Pearson correlation analysis showed that the reduced GMV in the right DLPFC and the right occipital pole was both positively correlated with Mini-Mental State Examination (MMSE) (r = 0.755, p < 0.001; r = 0.686, p = 0.002) and Montreal Cognitive Assessment (MoCA) scores (r = 0.716, p = 0.001; r = 0.601, p = 0.008), and the reduced GMV in the right occipital pole was negatively correlated with duration of illness (r = −0.497, p = 0.036). Patients with OSA have abnormal blood perfusion metabolism and morphological changes in brain regions including the frontal lobe and the cerebellum and were closely related to abnormal behavior, psychology, and cognitive function, which play an important role in the pathophysiological mechanism of OSA.

In this study, a multi-residue determination method of QuECHERS combined with UHPLC-MS/MS was developed to determine nine β-lactam antibiotics (penicillin G, amoxicillin, ampicillin, cephalexin, cefquinome, ceftiofur, cefazolin, cephapirin, cefuroxime) in aquaculture products. All the nine β-lactam antibiotics exhibited excellent linearity within the range of 2.0–200 ng/mL (cefuroxime: 5.0–200 ng/mL, r greater than 0.999), while the limits of detection (LODs) and quantification (LOQs) were 2.0–5.0 μg/kg and 5.0–10.0 μg/kg, respectively. The recoveries of this method in five aquaculture products (Penaeus Orientalis, Cyprinus Carpio, Channa Argus, Aristichthys Nobilis, and Ctenopharyngodon Idella) ranged from 85.4% to 113.3% and the intra-day and inter-day precisions (%RSDs) were less than 15%. The results suggested the feasibility of this method as a rapid, simple, and accurate approach for determining the residues of the β-lactam antibiotics in aquaculture products.

Summary: Background: Oral pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) can effectively prevent HIV infections among men who have sex with men (MSM), but the emergence and transmission of HIV drug-resistance (HIVDR) may compromise their benefits. The costs and benefits of expanding PrEP and ART coverage in the presence of HIVDR in China remain unknown. Methods: We developed a comprehensive dynamic transmission model incorporating the transmitted (TDR) and acquired (ADR) HIV drug resistance. The model was calibrated by the HIV surveillance data from 2009 to 2019 among MSM in Jiangsu Province, China, and validated by the dynamic prevalence of ADR and TDR. We aimed to investigate the impact of eight intervention scenarios (no PrEP, 20%, 50% or 80% of PrEP, without (77% coverage) or with (90% coverage) expanded ART) on the HIV epidemic trend and cost-effectiveness of PrEP over the next 30 years. Findings: 20% or 50% PrEP + 90% ART would be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 25,417 (95% confidence interval [CI]: 12,390–38,445) or 47,243 (23,756–70,729), and would yield 154,949 (89,662–220,237) or 179,456 (102,570–256,342) incremental quality-adjusted life-years (QALYs) over the next 30 years. No PrEP + 90% ART would yield 125,211 (73,448–176,974) incremental QALYs and be cost-saving. However, 20–80% PrEP + 77% ART and 80% PrEP + 90% ART with ICER of $77,862–$98,338 and $63,332, respectively, and were not cost-effective. A reduction of 64% in the annual cost of oral PrEP would make it highly cost-effective for 50% PrEP + 90% ART. Interpretation: 20% or 50% PrEP + 90% ART is cost-effective for HIV control in the presence of HIVDR. Expanded ART alone may be the optimal policy under the current limited budgets. Funding: National Natural Science Foundation of China, the National S&T Major Project Foundation of China.

Objective To compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L‐DAA) and supine position (S‐DAA) for unilateral total hip arthroplasty. Methods A retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L‐DAA and 43 patients who underwent S‐DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P

Abstract Form‐wound windings in electric machines designed for electric aircraft propulsion face reliability challenges due to the severe operating environment, such as high temperature and low pressure. This study proposes a forewarning method for insulation condition monitoring of form‐wound windings based on partial discharge (PD) and deep learning neural network. Three PD features are extracted from the PD profile, which provides information about physics‐of‐failure and reflects the degree of insulation degradation. An algorithm fusion extracted from auto‐encoder and long short‐term recurrent neural network is proposed to synthesize one failure precursor from these three features and make multi‐time‐step prediction through historical data to provide forewarning. An electrical and thermal accelerated ageing test is performed on the form‐wound windings at 0.2 atm to simulate working environment of electric aircraft. The proposed method is validated on the accelerated ageing dataset and shows better prediction accuracy than some existing time‐series prediction methods, indicating the advantages of the proposed method. Moreover, an on‐line hardware setup using a deep learning processor is recommended to implement the forewarning method. The proposed approach has the potential to be widely applied to other insulation systems and contribute to work on condition monitoring.

The global pandemic of 2019 coronavirus disease (COVID-19) is a great assault to public health. Presymptomatic transmission cannot be controlled with measures designed for symptomatic persons, such as isolation. This study aimed to estimate the interval of the transmission generation (TG) and the presymptomatic period of COVID-19, and compare the fitting effects of TG and serial interval (SI) based on the SEIHR model incorporating the surveillance data of 3453 cases in 31 provinces. These data were allocated into three distributions and the value of AIC presented that the Weibull distribution fitted well. The mean of TG was 5.2 days (95% CI: 4.6–5.8). The mean of the presymptomatic period was 2.4 days (95% CI: 1.5–3.2). The dynamic model using TG as the generation time performed well. Eight provinces exhibited a basic reproduction number from 2.16 to 3.14. Measures should be taken to control presymptomatic transmission in the COVID-19 pandemic.

Understanding the relation of different electronic orders in high temperature superconductors is of fundamental interest. Here, the authors observe a checkerboard charge order along [110] direction of FeSe.

Designing a strong tissue adhesive and multifunctional hydrogel dressing for various skin injuries is still a significant challenge. Based on the bioactive activities of rosmarinic acid (RA) and its catechol structure being similar to dopamine, RA-grafted dextran/gelatin hydrogel (ODex−AG−RA) was designed and systemically characterized in this study. The ODex−AG−RA hydrogel exhibited excellent physicochemical properties, including fast gelation time (61.6 ± 2.8 s), strong adhesive strength (27.30 ± 2.02 kPa) and enhanced mechanical properties (1.31 × 104 Pa of G′). The examination of hemolysis and co-culturing with L929 cells showed the strong in vitro biocompatibility of ODex−AG−RA hydrogels. The ODex−AG−RA hydrogels exhibited a 100% mortality rate against S. aureus and at least 89.7% against E. coli in vitro. In vivo evaluation for efficacy in skin wound healing was carried out in a rat model of full-thickness skindefect. The amount of collagen deposition and CD31 on wounds in the two ODex−AG−RA−1 groups on day 14 was 4.3 times and 2.3 times of that in the control group, respectively. Furthermore, the mechanism of ODex−AG−RA−1 for promoting wound healing was proved to be related to its anti-inflammatory properties by adjusting the expression of inflammatory cytokines (TNF-α and CD163) and reducing the level of oxidative stress (MDA and H2O2). Overall, this study demonstrated the wound-healing efficacy of RA-grafted hydrogels for the first time. ODex−AG−RA−1 hydrogel, due to its adhesive, anti-inflammatory, antibacterial and antioxidative activities, was a promising candidate as a wound dressing.

Abstract In this paper, the effect of moisture on the charge behaviour in oil‐impregnated pressboard is analysed based on the characteristics of the interface and the bulk. Space charge behaviour and infrared spectra are acquired from a sample with a high moisture content of 1.92% and another with low moisture content of 0.13%. The results show that a greater number of hydrogen bonds form in the high‐moisture sample. The threshold fields of charge injection are 1 and 0.6 kV/mm in the low‐ and high‐moisture samples, respectively. The dynamic charge transport in bulk is significantly accelerated by moisture. The drop in the injection barrier at the interface and the accelerated transport of charge in bulk in the high‐moisture sample may be associated with the mediating effect of a water layer at the interface and the lower trap energy in bulk caused by the hydrogen bonds, respectively. The combined changes in the interface and the bulk led to the dominant position of negative charges inside the high‐moisture sample, regardless of the distribution area or the charge amount.

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.