The enormous repetitive Antarctic krill genome reveals environmental adaptations and population insights.

Antarctic krill (Euphausia superba) is Earth's most abundant wild animal, and its enormous biomass is vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level Antarctic krill genome, whose large genome size appears to have resulted from inter-genic transposable element expansions. Our assembly reveals the molecular architecture of the Antarctic krill circadian clock and uncovers expanded gene families associated with molting and energy metabolism, providing insights into adaptations to the cold and highly seasonal Antarctic environment. Population-level genome re-sequencing from four geographical sites around the Antarctic continent reveals no clear population structure but highlights natural selection associated with environmental variables. An apparent drastic reduction in krill population size 10 mya and a subsequent rebound 100 thousand years ago coincides with climate change events. Our findings uncover the genomic basis of Antarctic krill adaptations to the Southern Ocean and provide valuable resources for future Antarctic research.

An Active Strategy Based on Different Droplet Removal Modes on Polydimethylsiloxane Magnetic Microstructures.

The efficient removal of droplets on solid surfaces holds significant importance in the field of fog collection, condensation heat transfer, and so on. However, on current typical surfaces, droplets are characterized by a passive and single removal mode, contingent on the traction force (e.g., capillary force, Laplace pressure, etc.) generated by the surface's physics and chemistry design, posing challenges for enhancing the efficiency of droplet removal. In this paper, an effective active strategy based on different removal modes is demonstrated on magnetic responsive polydimethylsiloxane (PDMS) superhydrophobic microplates (RM-MPSM). By regulating the parameters of microplates and droplet volume, different effective departure modes (top jumping and side departure) can be induced to facilitate the removal of droplets. Moreover, the removal volume of droplets through the side departure mode exhibits a significant reduction compared to that observed in the top jumping mode. The exceptional removal ability of RM-MPSM demonstrates adaptability to diverse functional applications: efficient fog collection, removal of condensation droplets and micro-particles. The efficient modes of droplet removal demonstrated in this work hold significant implications for broadening its application in many fields, such as droplet collection, heat transfer, and anti-icing.

Elevated aerobic glycolysis driven by p62-mTOR axis promotes arsenic-induced oncogenic phenotypes in human mammary epithelial cells.

Chronic arsenic exposure is considered to increase the risk of breast cancer. p62 is a multifunctional adaptor protein that controls myriad cellular processes and is overexpressed in breast cancer tissues. Although previous studies have indicated the involvement of p62 accumulation in arsenic tumorigenesis, the underlying mechanism remains obscure. Here, we found that 0.1 µM or 0.5 µM arsenite exposure for 24 weeks induced oncogenic phenotypes in human mammary epithelial cells. Elevated aerobic glycolysis, cell proliferation capacity, and activation of p62-mTOR pathway, as indicated by increased protein levels of p62, phosphorylated-mTOR (p-mTOR) and hypoxia-inducible factor 1α (HIF1α), were observed in chronically arsenite-exposed cells, and of note in advance of the onset of oncogenic phenotypes. Moreover, p62 silencing inhibited acquisition of oncogenic phenotypes in arsenite-exposed cells. The protein levels of p-mTOR and HIF1α, as well as aerobic glycolysis and cell proliferation, were suppressed by p62 knockdown. In addition, re-activation of p­mTOR reversed the inhibitory effects of p62 knockdown. Collectively, our data suggest that p62 exerts an oncogenic role via mTORC1 activation and acts as a key player in glucose metabolism during arsenite-induced malignant transformation, which provides a new mechanistic clue for the arsenite carcinogenesis.

Advances in the Application of AI Robots in Critical Care: Scoping Review.

BACKGROUND: In recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. OBJECTIVE: This review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. METHODS: Following the scoping review framework proposed by Arksey and O'Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. RESULTS: Of the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. CONCLUSIONS: This review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

The urinary level of 2,4,5-trichlorophenol was positively associated with both all-cause and cause-specific mortalities in general adult residents of United States.

Chlorophenols are widespread environmental organic pollutants with harmful effects on human beings. Although relationships between chlorophenols and various dysfunctions/diseases have been reported, the contribution of chlorophenols exposure to mortalities is underdetermined. In this cohort study, we included 4 types of urinary chlorophenols, aiming to estimate associations of chlorophenols exposure with all-cause and cause-specific mortalities. Urinary chlorophenols were examined at baseline of National Health and Nutrition Examination Survey (NHANES) 2003-2010, and adjusted for the urinary creatinine level. Associations between chlorophenols and mortalities were estimated using COX regression analyses, results were shown as hazard ratio (HR) and 95% confidence interval (95% CI). By dividing participants into four subgroups based on quartiles of urinary levels of chlorophenols, associations between mortalities and categorical variables of chlorophenols were estimated. Furthermore, the quantile g-computation analysis was used to estimate the joint effects of 4 chlorophenols on mortalities. Among 5817 adults (2863 men), 1034 were deceased during the follow-up. After adjusted for confounders, 2,4,5-trichlorophenol (2,4,5-TCP) was found to be positively associated with both all-cause (HR = 1.46; 95% CI: 1.16, 1.84) and cardiovascular disease (CVD) mortalities (HR = 1.60; 95% CI: 1.00, 2.55). Compared to the subgroup of the lowest level of chlorophenols, participants in subgroups of higher 2,4,5-TCP levels showed higher risk of all-cause mortality (P-value for trend = 0.003). For CVD mortality, HRs in subgroups of higher levels of 2,4-dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) were statistically significant (P-values for trend were 0.017 for 2,4-DCP and 0.049 for 2,4,6-TCP). The HRs (95% CI) of joint effects of 4 chlorophenols were 1.11 (1.01, 1.21) and 1.32 (1.10, 1.57) for all-cause and CVD-specific mortalities, and 2,4,5-TCP showed the highest weight in joint effects. All of these findings implied that among 4 urinary chlorophenols we included, 2,4,5-TCP might be a sensitive one in associations with mortalities among general populations.

Arginine Biosynthesis Mediates Wulingzhi Extract Resistance to Busulfan-Induced Male Reproductive Toxicity.

Busulfan, an indispensable medicine in cancer treatment, can cause serious reproductive system damage to males as a side effect of its otherwise excellent therapeutic results. Its widespread use has also caused its accumulation in the environment and subsequent ecotoxicology effects. As a Chinese medicine, Wulingzhi (WLZ) has the effects of promoting blood circulation and improving female reproductive function. However, the potential effects of WLZ in male reproduction and in counteracting busulfan-induced testis damage, as well as its probable mechanisms, are still ambiguous. In this study, busulfan was introduced in a mouse model to evaluate its production of the testicular damage. The components of different WLZ extracts were compared using an untargeted metabolome to select extracts with greater efficacy, which were further confirmed in vivo. Here, we demonstrate abnormal spermatogenesis and low sperm quality in busulfan-injured testes. The WLZ extracts showed a strong potential to rehabilitate the male reproductive system; this effect was more prominent in room-temperature extracts. Additionally, both water and ethanol WLZ extracts at room temperature alleviated various busulfan-induced adverse effects. In particular, WLZ recovered spermatogenesis, re-activated arginine biosynthesis, and alleviated the increased oxidative stress and inflammation in the testis, ultimately reversing the busulfan-induced testicular injury. Collectively, these results suggest a promising approach to protecting the male reproductive system from busulfan-induced adverse side effects, as well as those of other similar anti-cancer drugs.

Dynamic interplay between the co-opted Fis1 mitochondrial fission protein and membrane contact site proteins in supporting tombusvirus replication.

Plus-stranded RNA viruses have limited coding capacity and have to co-opt numerous pro-viral host factors to support their replication. Many of the co-opted host factors support the biogenesis of the viral replication compartments and the formation of viral replicase complexes on subverted subcellular membrane surfaces. Tomato bushy stunt virus (TBSV) exploits peroxisomal membranes, whereas the closely-related carnation Italian ringspot virus (CIRV) hijacks the outer membranes of mitochondria. How these organellar membranes can be recruited into pro-viral roles is not completely understood. Here, we show that the highly conserved Fis1 mitochondrial fission protein is co-opted by both TBSV and CIRV via direct interactions with the p33/p36 replication proteins. Deletion of FIS1 in yeast or knockdown of the homologous Fis1 in plants inhibits tombusvirus replication. Instead of the canonical function in mitochondrial fission and peroxisome division, the tethering function of Fis1 is exploited by tombusviruses to facilitate the subversion of membrane contact site (MCS) proteins and peroxisomal/mitochondrial membranes for the biogenesis of the replication compartment. We propose that the dynamic interactions of Fis1 with MCS proteins, such as the ER resident VAP tethering proteins, Sac1 PI4P phosphatase and the cytosolic OSBP-like oxysterol-binding proteins, promote the formation and facilitate the stabilization of virus-induced vMCSs, which enrich sterols within the replication compartment. We show that this novel function of Fis1 is exploited by tombusviruses to build nuclease-insensitive viral replication compartment.

Drug-drug interaction potential of SH-1028, a third-generation EGFR-TKI: in vitro and clinical trials.

SH-1028 is an irreversible third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Considering the possibility of combination therapy in patients with NSCLC, we investigated the drug-drug interaction (DDI) potential of SH-1028 both in vitro and in clinical trials. The in vitro studies were conducted to determine the potential of SH-1028 as a substrate, inducer, or inhibitor of cytochrome P450 (CYP) subtypes. A phase I drug-drug interaction study in healthy volunteers was performed to evaluate the impact of co-administering rifampicin (a strong CYP3A4 inducer) and itraconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics of SH-1028. The in vitro experiments showed that SH-1028 was mainly metabolized by CYP3A4. The activities of CYP1A2, 2B6, 2C19, 2D6 and 3A4 enzymes were slightly inhibited in vitro with SH-1028. SH-1028 has no obvious induction effect on CYP1A2 and CYP2B6 activities, but has potential induction effect on CYP3A4 mRNA expression. However, SH-1028 may not induce or inhibit human CYPs significantly at the clinically expected dose (200 mg). The geometric mean ratios of pharmacokinetic parameters and their corresponding 90% confidence intervals for SH-1028 in combination and alone did not fall within the range of 80-125%. It is speculated that itraconazole and rifampicin affect the metabolism of SH-1028. In the clinical application of SH-1028, special attention should be paid to the interaction between SH-1028 and drugs or foods that affect the activity of CYP3A4. (Clinical trial registration number: CTR20210558).

Fe(II)-Catalyzed Transformation of Ferrihydrite with Different Degrees of Crystallinity.

Natural occurring ferrihydrite (Fh) nanoparticles have varying degrees of crystallinity, but how Fh crystallinity affects its transformation behavior remains elusive. Here, we investigated the Fe(II)-catalyzed transformation of Fh with different degrees of crystallinity (i.e., Fh-2h, Fh-12h, and Fh-85C). X-ray diffraction patterns of Fh-2h, Fh-12h, and Fh-85C exhibited two, five, and six diffraction peaks, respectively, indicating the order of crystallinity: Fh-2h < Fh-12h < Fh-85C. Fh with the lower crystallinity has a higher redox potential, corresponding to the faster Fe(II)-Fh interfacial electron transfer and Fe(III)labile production. With the increase of initial Fe(II) concentration ([Fe(II)aq]int.) from 0.2 to 5.0 mM, the transformation pathways of Fh-2h and Fh-12h change from Fh → lepidocrocite (Lp) → goethite (Gt) to Fh → Gt, but that of Fh-85C switches from Fh → Gt to Fh → magnetite (Mt). The changes are rationalized using a computational model that quantitatively describes the relationship between the free energies of formation for starting Fh and nucleation barriers of competing product phases. Gt particles from the Fh-2h transformation exhibit a broader width distribution than those from Fh-12h and Fh-85C. Uncommon hexagonal Mt nanoplates are formed from the Fh-85C transformation at [Fe(II)aq]int.= 5.0 mM. The findings are crucial to comprehensively understand the environmental behavior of Fh and other associated elements.

Dietary intakes of methionine, threonine, lysine, arginine and histidine increased risk of type 2 diabetes in Chinese population: does the mediation effect of obesity exist?

BACKGROUND: Published studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population. METHODS: A total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated. RESULTS: Higher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid. CONCLUSIONS: We found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.

Anti-inflammatory effect and mechanism of catalpol in various inflammatory diseases.

Catalpol is a kind of iridoid glucoside, widely found in a variety of plants, mostly extracted from the rhizome of the traditional medicinal herb rehmanniae. It has various biological activities such as anti-inflammatory, antioxidant, and antitumor. The anti-inflammatory effects of catalpol have been demonstrated in a variety of diseases, such as neurological diseases, atherosclerosis, renal diseases, respiratory diseases, digestive diseases, bone and joint diseases, eye diseases, and periodontitis. The purpose of this review is to summarize the existing literature on the anti-inflammatory effects of catalpol in a variety of inflammatory diseases over the last decade and to focus on the anti-inflammatory mechanisms of catalpol.

Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke.

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.

Comparison of therapies of white spot lesions: a systematic review and network meta-analysis.

OBJECTIVE: White spot lesions (WSLs), the earliest evidence of enamel demineralization, are considered amenable to intervention to achieve a remineralized or arrested state of caries. The management of WSLs is quite challenging, and there is no definitive cure as yet. We performed a network meta-analysis to assess the efficacy of seven therapies for WSLs and gave a hierarchy of them. MATERIALS AND METHODS: We systematically searched the PubMed, EMBASE, Cochrane, and Web of Science databases (last search: July 2022) to identify all relevant studies. We limited our search to studies published in English. Randomized controlled designed in vitro/clinical trials related to the efficacy of the seven therapies for WSLs were included. Data extraction was performed independently by two reviewers. The risk of bias (ROB) 2.0 tool from Cochrane and a previous in vitro methodological tool will be used for the quality assessment. Variations in quantitative light-induced fluorescence (QLF), laser fluorescence (LF), and lesions area were the primary outcome measures. Standard mean difference (SMD) was used as the effect size for the Network meta-analysis (NMA). Consistency and inconsistency tests were conducted. The hierarchy of 7 treatment effects was evaluated using surface probabilities under cumulative ranking (SUCRA). Publication bias was evaluated using a bias plot. RESULTS: Forty-two articles were included in the systematic review. Thirty-one of them, with a total of 1906 participants, were included in the network meta-analysis. The studies owned a low and moderate risk of bias. This analysis does not suffer from significant inconsistency. The difference between 4 groups 'self-assembled peptide (SAP) P11-4', 'P11-4 + Fluoride Varnish (FV)', 'Resin Infiltration (RI)', 'casein phosphor peptides-amorphous calcium fluoride phosphate (CPP-ACFP)' and the 'Control' group was found to be statistically significant. Compared to the 'FV' and 'casein phosphor peptides-amorphous calcium phosphate (CPP-ACP)' groups, the 'P11-4 + FV" group and 'RI" group made a significant difference. The hierarchy was evident in the SUCRA values of 7 therapies. P11-4 + FV and RI were considered effective therapies compared to the control group or the FV group (gold standard group). CONCLUSIONS: The available evidence suggests that resin infiltration and P11-4 in combination with fluoride varnish had advantages over gold standard (FV). The effect of tricalcium phosphate-based drugs and fluoride is not very noticeable. Overall, drugs based on P11-4 and resin infiltration will be better therapies. Using more than two drugs in combination also would increase efficacy.

Self-Transportation of Superparamagnetic Droplets on a Magnetic Gradient Slippery Surface with On/Off Sliding Controllability.

Recently, research about droplet self-transportation on slippery surfaces has become a hotspot. However, to achieve on/off sliding control during the self-transportation process is still difficult. Herein, we report a magnetic slippery surface, and demonstrate on/off sliding control during the self-transportation of superparamagnetic droplets. The surface is prepared through integrating a substrate that has a gradient magnetic region with a layer of paraffin infused hydrophobic SiO2 nanoparticles. On the surface, a superparamagnetic droplet is pinned at room temperature (about 25 °C), while it can self-transport directionally as the temperature is increased to about 70 °C. When the temperature is cooled down again, the droplet would return to the pinned state, indicating that on/off sliding control during the self-transportation process can be achieved. Furthermore, based on the excellent controllability, controllable coalescence of two droplets from opposite direction is displayed, demonstrating its potential application in numerous areas.

An Energy-Efficient BJT-Based Temperature Sensor with ±0.8 °C (3σ) Inaccuracy from -50 to 150 °C.

This article presents an energy-efficient BJT-based temperature sensor. The output of sensing front-ends is modulated by employing an incremental Δ-Σ ADC as a readout interface. The cascoded floating-inverter-based dynamic amplifier (FIA) is used as the integrator instead of the conventional operational transconductance amplifier (OTA) to achieve a low power consumption. To enhance the accuracy, chopping and dynamic element matching (DEM) are applied to eliminate the component mismatch error while ß-compensation resistor and optimized bias current are used to minimize the effect of ß variation. Fabricated in a standard 180-nm CMOS process, this sensor has an active area of 0.13 mm2. While dissipating only 45.7 µW in total, the sensor achieves an inaccuracy of ±0.8 °C (3σ) from -50 °C to 150 °C after one-point calibration.

Applications of Titanium Dioxide Nanostructure in Stomatology.

Breakthroughs in the field of nanotechnology, especially in nanochemistry and nanofabrication technologies, have been attracting much attention, and various nanomaterials have recently been developed for biomedical applications. Among these nanomaterials, nanoscale titanium dioxide (nano-TiO2) has been widely valued in stomatology due to the fact of its excellent biocompatibility, antibacterial activity, and photocatalytic activity as well as its potential use for applications such as dental implant surface modification, tissue engineering and regenerative medicine, drug delivery carrier, dental material additives, and oral tumor diagnosis and treatment. However, the biosafety of nano-TiO2 is controversial and has become a key constraint in the development of nano-TiO2 applications in stomatology. Therefore, in this review, we summarize recent research regarding the applications of nano-TiO2 in stomatology, with an emphasis on its performance characteristics in different fields, and evaluations of the biological security of nano-TiO2 applications. In addition, we discuss the challenges, prospects, and future research directions regarding applications of nano-TiO2 in stomatology that are significant and worthy of further exploration.

Solid-liquid partitioning and variation of palladium in rainfall runoff.

Palladium (Pd) is most widely used in the production of automotive catalytic converters that serve to reduce toxic emissions from motor vehicles. The aim of this study was to analyze the solid-liquid partitioning and dynamic variation of Pd in rainfall runoff. The results showed that the partition coefficients (K) of Pd ranged from 0.05 to 8.55. Transport via suspended particulate matter as the main carrier was the main form of Pd migration in rainfall runoff. Pd phase distribution exhibited complex dynamic variations. The variation in Pd could be roughly divided into three categories, namely the W, M and N types, and the semi-U type was also observed. Rainfall characteristics and microenvironmental factors had a profound effect on Pd phase distribution in the first flush runoff. Under the influence of multifactor coupling, the impact of water quality parameters such as pH, Eh and Cl- on Pd partitioning was significantly weakened.

The temporal distribution of platinum group elements (PGEs) in PM2.5.

In this paper, Changji, Xinjiang, northwest China, was selected as the study area, and platinum group elements (PGEs) in PM2.5 were quantified by ICP-MS using microwave digestion. The results indicated that the average concentrations (and range) of Rh, Pd, and Pt in PM2.5 were 0.21 (n.d. -1.41) ng/m3, 8.09 (n.d. -59.50) ng/m3, and 0.12 (n.d. -0.83) ng/m3, respectively. The concentration of Pd was significantly higher than Rh and Pt. Moreover, the seasonal variations of Rh and Pd were the same: highest in summer and lower in other seasons. However, the seasonal variation of Pt was opposite to that of Rh and Pd: highest in winter and lower in other seasons. Seasonal differences in emission sources of PGEs and the climatic characteristics of arid regions played important roles in the seasonal changes of PGEs. Rh and Pd had a common source and similar diurnal variation. The major influencing factors were traffic volume and meteorological conditions. The diurnal variation regularity of Pt was different from Rh and Pd. The superimposed effect of vehicle exhaust emissions and coal-fired emissions was the main reason why the diurnal variation of Pt was more complicated than those of Rh and Pd. The diurnal concentration of Pt varied with the seasons. It is caused by seasonal coal combustion and meteorological conditions.

Co-opting the fermentation pathway for tombusvirus replication: Compartmentalization of cellular metabolic pathways for rapid ATP generation.

The viral replication proteins of plus-stranded RNA viruses orchestrate the biogenesis of the large viral replication compartments, including the numerous viral replicase complexes, which represent the sites of viral RNA replication. The formation and operation of these virus-driven structures require subversion of numerous cellular proteins, membrane deformation, membrane proliferation, changes in lipid composition of the hijacked cellular membranes and intensive viral RNA synthesis. These virus-driven processes require plentiful ATP and molecular building blocks produced at the sites of replication or delivered there. To obtain the necessary resources from the infected cells, tomato bushy stunt virus (TBSV) rewires cellular metabolic pathways by co-opting aerobic glycolytic enzymes to produce ATP molecules within the replication compartment and enhance virus production. However, aerobic glycolysis requires the replenishing of the NAD+ pool. In this paper, we demonstrate the efficient recruitment of pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) fermentation enzymes into the viral replication compartment. Depletion of Pdc1 in combination with deletion of the homologous PDC5 in yeast or knockdown of Pdc1 and Adh1 in plants reduced the efficiency of tombusvirus replication. Complementation approach revealed that the enzymatically functional Pdc1 is required to support tombusvirus replication. Measurements with an ATP biosensor revealed that both Pdc1 and Adh1 enzymes are required for efficient generation of ATP within the viral replication compartment. In vitro reconstitution experiments with the viral replicase show the pro-viral function of Pdc1 during the assembly of the viral replicase and the activation of the viral p92 RdRp, both of which require the co-opted ATP-driven Hsp70 protein chaperone. We propose that compartmentalization of the co-opted fermentation pathway in the tombusviral replication compartment benefits the virus by allowing for the rapid production of ATP locally, including replenishing of the regulatory NAD+ pool by the fermentation pathway. The compartmentalized production of NAD+ and ATP facilitates their efficient use by the co-opted ATP-dependent host factors to support robust tombusvirus replication. We propose that compartmentalization of the fermentation pathway gives an evolutionary advantage for tombusviruses to replicate rapidly to speed ahead of antiviral responses of the hosts and to outcompete other pathogenic viruses. We also show the dependence of turnip crinkle virus, bamboo mosaic virus, tobacco mosaic virus and the insect-infecting Flock House virus on the fermentation pathway, suggesting that a broad range of viruses might induce this pathway to support rapid replication.

Mesenchymal stem cells regulate activation of microglia cells to improve hippocampal injury of heat stroke rats.

Heat stroke is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Mesenchymal stem cells (MSCs) are currently believed to have anti-inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on heat stroke-induced excessive inflammation and neurological dysfunction. We established a heat stroke model in rats under conditions of continuous high temperature and high humidity. After modeling, rats were randomly divided into heat stroke model group, MSCs treatment group and normal temperature control group without any treatment. We performed survival analysis, neurological deficit score, histological staining of hippocampus and cerebellum, immunofluorescence staining of microglia, detection of inflammatory and chemokine levels in the hippocampus and cerebellum in each group. We found that MSCs treatment not only significantly reduced early (day 3) and late (day 28) mortality, but also prominently reduced nerve injury in heat stroke rats, and improved pathology and neuronal cell damage in the hippocampus and cerebellum. In addition, MSCs treatment can significantly inhibit the over-activation of hippocampal microglia in heat stroke rats and the levels of pro-inflammatory factors and chemokines in the hippocampus. Early treatment of MSCs can greatly promote the activation of cerebellar microglia in heat stroke rats. Meanwhile, MSCs treatment has an inhibitory effect on the level of chemokine in the cerebellum of rats in the early stage of heat stroke. In conclusion, the application of MSCs in the treatment of heat stroke in rats can significantly reduce mortality and neurological deficits and improve hippocampal damage, possibly by inhibiting the excessive activation of hippocampal microglia in heat stroke rats.