Communication-Efficient Cooperative Multi-Agent PPO via Regulated Segment Mixture in Internet of Vehicles

Multi-Agent Reinforcement Learning (MARL) has become a classic paradigm to solve diverse, intelligent control tasks like autonomous driving in Internet of Vehicles (IoV). However, the widely assumed existence of a central node to implement centralized federated learning-assisted MARL might be impractical in highly dynamic scenarios, and the excessive communication overheads possibly overwhelm the IoV system. Therefore, in this paper, we design a communication efficient cooperative MARL algorithm, named RSM-MAPPO, to reduce the communication overheads in a fully distributed architecture. In particular, RSM-MAPPO enhances the multi-agent Proximal Policy Optimization (PPO) by incorporating the idea of segment mixture and augmenting multiple model replicas from received neighboring policy segments. Afterwards, RSM-MAPPO adopts a theory-guided metric to regulate the selection of contributive replicas to guarantee the policy improvement. Finally, extensive simulations in a mixed-autonomy traffic control scenario verify the effectiveness of the RSM-MAPPO algorithm

Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy

Autism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit gene GABRA4 are reported in patients with ASD, we eliminated the Gabra4 gene in mice and found that the Gabra4 knockout mice showed autistic-like behavior, enhanced spatial memory, and attenuated susceptibility to pentylenetetrazol-induced seizures, a constellation of symptoms resembling human high-functioning autism. To search for potential molecular pathways involved in these phenotypes, we performed a hippocampal transcriptome profiling, constructed a hippocampal interactome network, and revealed an upregulation of the NMDAR system at the center of the converged pathways underlying high-functioning autism-like and anti-epilepsy phenotypes

Genetic effects on tolerance to acute cold stress in red drum, Sciaenops ocellatus L

Abstract Genetic e¡ects on cold-stress tolerance were assessed for red drum (Sciaenops ocellatus), an economically important sciaenid ¢sh in the southern USA. Thirty¢ve families were generated via 'natural'spawning of multiple sets of ¢ve breeders (three dams  two sires) in individual brood tanks. O¡spring from the 35 families were transferred abruptly from an acclimation temperature of $24 1C to 5.7 1C and maintained subsequently at an average temperature of 6.5 1C. O¡spring were assigned a posteriori to individual brood¢sh (dam and sire) based on genotypes at nuclear-encoded microsatellites. Heritability of the survival^time probability function was estimated using a proportional hazard approach and an animaladditive model. The estimated heritability was 0.20 (95% CI: 0.07^0.40), indicating a signi¢cant genetic component to acute cold-stress tolerance in red drum

Prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia

Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.  Objectives: To evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathogens in common LRIs through a large-scale prospective study.  Methods: We enrolled 292 hospitalized patients suspected to have LRIs between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests.  Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRIs. The turnaround time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR validation tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation between enriched anaerobes and lung abscess was observed by Gene Set Enrichment Analysis. Moreover, 38 anaerobic species failed in culture was identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture.  Conclusions: Rapid clinical metagenomics test improved pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management

Structure of HsdS Subunit from Thermoanaerobacter tengcongensis Sheds Lights on Mechanism of Dynamic Opening and Closing of Type I Methyltransferase

Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 Å crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase

Confinement of carbon dots localizing to the ultrathin layered double hydroxides toward simultaneous triple-mode bioimaging and photothermal therapy

It is a great challenge to develop multifunctional nanocarriers for cancer diagnosis and therapy. Herein, versatile CDs/ICG-uLDHs nanovehicles for triple-modal fluorescence/photoacoustic/two-photon bioimaging and effective photothermal therapy were prepared via a facile self-assembly of red emission carbon dots (CDs), indocyanine green (ICG) with the ultrathin layered double hydroxides (uLDHs). Due to the J-aggregates of ICG constructed in the self-assembly process, CDs/ICG-uLDHs was able to stabilize the photothermal agent ICG and enhanced its photothermal efficiency. Furthermore, the unique confinement effect of uLDHs has extended the fluorescence lifetime of CDs in favor of bioimaging. Considering the excellent in vitro and in vivo phototherapeutics and multimodal imaging effects, this work provides a promising platform for the construction of multifunctional theranostic nanocarrier system for the cancer treatment

Attenuating effect of Polygala tenuifolia Willd. seed oil on progression of MAFLD

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs).Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses.Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level.Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD

The intervention of classical and molecular breeding approaches to enhance flooding stress tolerance in soybean – An review

Abiotic stresses and climate changes cause severe loss of yield and quality of crops and reduce the production area worldwide. Flooding stress curtails soybean growth, yield, and quality and ultimately threatens the global food supply chain. Flooding tolerance is a multigenic trait. Tremendous research in molecular breeding explored the potential genomic regions governing flood tolerance in soybean. The most robust way to develop flooding tolerance in soybean is by using molecular methods, including quantitative trait loci (QTL) mapping, identification of transcriptomes, transcription factor analysis, CRISPR/Cas9, and to some extent, genome-wide association studies (GWAS), and multi-omics techniques. These powerful molecular tools have deepened our knowledge about the molecular mechanism of flooding stress tolerance. Besides all this, using conventional breeding methods (hybridization, introduction, and backcrossing) and other agronomic practices is also helpful in combating the rising flooding threats to the soybean crop. The current review aims to summarize recent advancements in breeding flood-tolerant soybean, mainly by using molecular and conventional tools and their prospects. This updated picture will be a treasure trove for future researchers to comprehend the foundation of flooding tolerance in soybean and cover the given research gaps to develop tolerant soybean cultivars able to sustain growth under extreme climatic changes

Emergence of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Coharboring a blaNDM-1-Carrying Virulent Plasmid and a blaKPC-2-Carrying Plasmid in an Egyptian Hospital

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly blaNDM-1 and blaKPC-2. Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes blaNDM-1 and blaKPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the blaNDM-1 and virulence genes and a blaKPC-2-carrying plasmid