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Introduction: Golden pompano (Trachinotus ovatus) is economically significant important for offshore cage aquaculture in China and Southeast Asian countries. Lack of high-quality genomic data and accurate gene annotations greatly restricts its genetic breeding progress. Objectives: To decode the mechanisms of sex determination and rapid growth in golden pompano and facilitate the sex- and growth-aimed genetic breeding. Methods: Genome assemblies of male and female golden pompano were generated using Illumina, PacBio, BioNano, genetic maps and Hi-C sequencing data. Genomic comparisons, whole genome re-sequencing of 202 F1 individuals, QTL mapping and gonadal transcriptomes were used to analyze the sex determining region, sex chromosome evolution, SNP loci, and growth candidate genes. Zebrafish model was used to investigate the functions of growth candidate gene. Results: Female (644.45 Mb) and male (652.12 Mb) genomes of golden pompano were assembled and annotated at the chromosome level. Both genomes are highly conserved and no new or highly differentiated sex chromosomes occur. A 3.5 Mb sex determining region on LG15 was identified, where Hsd17b1, Micall2 and Lmx1a were putative candidates for sex determination. Three SNP loci significantly linked to growth were pinpointed, and a growth-linked gene gpsstr1 was identified by locus BSNP1369 (G → C, 17489695, Chr23). Loss of sstr1a (homologue of gpsstr1) in zebrafish caused growth retardation. Conclusion: This study provides insights into sex chromosome evolution, sex determination and rapid growth of golden pompano.

Leptospirosis is a common but underdiagnosed zoonosis. We conducted a 1-year prospective study in La Guaira State, Venezuela, analyzing 71 hospitalized patients who had possible leptospirosis and sampling local rodents and dairy cows. Leptospira rrs gene PCR test results were positive in blood or urine samples from 37/71 patients. Leptospira spp. were isolated from cultured blood or urine samples of 36/71 patients; 29 had L. interrogans, 3 L. noguchii, and 4 L. venezuelensis. Conjunctival suffusion was the most distinguishing clinical sign, many patients had liver involvement, and 8/30 patients with L. interrogans infections died. The Leptospira spp. found in humans were also isolated from local rodents; L. interrogans and L. venezuelensis were isolated from cows on a nearby, rodent-infested farm. Phylogenetic clustering of L. venezuelensis isolates suggested a recently expanded outbreak strain spread by rodents. Increased awareness of leptospirosis prevalence and rapid diagnostic tests are needed to improve patient outcomes.

Abstract The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p

The three programs that make up the Immune Mechanisms of Protection Against Mycobacterium tuberculosis Centers (IMPAc-TB) had to prioritize and select strains to be leveraged for this work. The CASCADE team based at Seattle Children’s Research Institute are leveraging M.tb H37Rv, M.tb CDC1551, and M.tb SA161. The HI-IMPACT team based at Harvard T.H. Chan School of Public Health, Boston, have selected M.tb Erdman as well as a novel clinical isolate recently characterized during a longitudinal study in Peru. The PHOENIX team also based at Seattle Children’s Research Institute have selected M.tb HN878 and M.tb Erdman as their isolates of choice. Here, we describe original source isolation, genomic references, key virulence characteristics, and relevant tools that make these isolates attractive for use. The global context for M.tb lineage 2 and 4 selection is reviewed including what is known about their relative abundance and acquisition of drug resistance. Host–pathogen interactions seem driven by genomic differences on each side, and these play an important role in pathogenesis and immunity. The few M.tb strains chosen for this work do not reflect the vast genomic diversity within this species. They do, however, provide specific virulence, pathology, and growth kinetics of interest to the consortium. The strains selected should not be considered as “representative” of the growing available array of M.tb isolates, but rather tools that are being used to address key outstanding questions in the field.

Abstract Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) – the variability of gene expression in response to environmental changes – remains largely unexplored. In this study, we investigate the genome-wide TP profiles of Mycobacterium tuberculosis (Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal that Mtb genes exhibit significant TP variation that correlates with gene function and gene essentiality. We also find that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two other Mycobacterium species -- M. smegmatis and M. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.

In complex off-road environments, different slopes, slope directions, and land types differently affect unmanned vehicle trafficability. Thus, we propose an unmanned vehicle off-road path-planning method with comprehensive constraints on multiple environmental factors. First, the influence of slope, aspect, and surface-coverage type on unmanned vehicle drivability was quantitatively evaluated, and the slope and land type influence layers were formed. Concurrently, a goal guidance layer was formed using the artificial potential field method. Second, the slope influence, land type influence, and goal guidance layers were used to quantitatively evaluate each grid’s pass cost value. Finally, the traditional A* algorithm, A* algorithm considering the impassable area, A* algorithm with comprehensive constraints, and Dijkstra algorithm with comprehensive constraints were used for path planning. The results show that the path slopes planned by A* algorithm with comprehensive constraints and Dijkstra algorithm with comprehensive constraints were smaller than those planned by A* algorithm and A* algorithm considering the impassable area; particularly, the length of the uphill path was shorter and the stability was better. The relevant research results provide methods and technical guidance for obtaining the shortest length, shortest time, and most stable and passable path in off-road environments.

ABSTRACTThe Earth’s nighttime light imaging data collected by the Visible Infrared Imaging Radiometer Suite Day/Night Band (VIIRS DNB) are severely lost in summer, hindering the further application of VIIRS DNB data. In this article, a spatiotemporal comprehensive constraint interpolation method (SCIM) that accounts for the relative stationarity of temporal nighttime light, spatial correlations and heterogeneity among pixels is designed. Meanwhile, the method considers the seasonal fluctuations in nighttime light radiation, introduces spatial autocorrelation coefficients and spatial heterogeneity coefficients, and solves the problem of missing VIIRS DNB data. First, 8 widely used temporal interpolation methods (TIM) are selected to perform temporal interpolation for missing image data. Second, the existing VIIRS monthly images are used to construct the constraint relationship between time and space, and the pixels that do not meet the constraint conditions in the TIM simulation image are removed. The inverse distance weight (IDW) method is applied to the removed null pixels to obtain the image simulated by the SCIM. Finally, the accuracy of the TIM and SCIM is evaluated. The results show that the accuracy of the SCIM-simulated image is better than that of the TIM-simulated image. The proposed approach improves the quality of the VIIRS DNB dataset.

Abstract The treatment of diabetic wounds faces enormous challenges due to complex wound environments, such as infected biofilms, excessive inflammation, and impaired angiogenesis. The critical role of the microenvironment in the chronic diabetic wounds has not been addressed for therapeutic development. Herein, we develop a microneedle (MN) bandage functionalized with dopamine-coated hybrid nanoparticles containing selenium and chlorin e6 (SeC@PA), which is capable of the dual-directional regulation of reactive species (RS) generation, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), in response to the wound microenvironment. The SeC@PA MN bandage can disrupt barriers in wound coverings for efficient SeC@PA delivery. SeC@PA not only depletes endogenous glutathione (GSH) to enhance the anti-biofilm effect of RS, but also degrades GSH in biofilms through cascade reactions to generate more lethal RS for biofilm eradication. SeC@PA acts as an RS scavenger in wound beds with low GSH levels, exerting an anti-inflammatory effect. SeC@PA also promotes the M2-phenotype polarization of macrophages, accelerating wound healing. This self-enhanced, catabolic and dynamic therapy, activated by the wound microenvironment, provides an approach for treating chronic wounds.

ObjectiveTo evaluate mutagenic and teratogenic effects of lanthanum nitrate for providing evidence to safe use of the rare earth element. MethodsThe mutagenicity of lanthanum nitrate was evaluated by micronucleus assay on mouse bone marrow cells, in vitro chromosome aberration test, and Salmonella typhimurium strains bacterial reverse mutation test and the teratogenic effect of lanthanum nitrate was assessed with teratogenicity test in rats. The micronucleus assay on mouse bone marrow cells was performed in three groups of ICR mice (10 in each group, half male and half female) administrated with lanthanum nitrate at concentrations (mg/kg·BW) of 875, 437.5, 218.75 for the male mice and 1015, 507.5, 253.75 for the female mice according to the median lethal dose (LD50) of lanthanum nitrate for the mice. The chromosome aberration test of mammalian cells in vitro was conducted on Chinese hamster lung (CHL) cells (with good growth during logarithmic division and inoculated into 25 mL cell culture bottle, 1 × 106 cells per bottle) treated with lanthanum nitrate at concentrations of 1 × 10 – 3, 1 × 10 – 4, 1 × 10 – 5 mol (without S9 mixture) and 5 × 10 – 3, 2.5 × 10 – 4,1.25 × 10 – 5 mol (with S9 mixture) based on the median inhibition concentration (IC50) of lanthanum nitrate on CHL cells. Five lanthanum nitrate dose groups (5, 1, 0.2, 0.04, 0.008 mg/dish, respectively) were set up to carry out Salmonella typhimurium (TA97, TA98, TA100, TA102, TA1535) strains bacterial reverse mutation test in the presence or absence of S9 metabolic activation system. In teratogenicity test on pregnant Sprague-Dawley (SD) rats (at least 15 in each group), three lanthanum nitrate dosages of (9, 36, 144 mg/kg·BW) were determined and the growth and implantation ability and the offspring rats′ weight and length, rate of skeletal malformation, rate of organ malformation and total rate of viscera malformation were oberserved. ResultsIn micronucleus assay, the micronucleus formation rates of bone marrow cells in each lanthanum nitrate dose group were similar with that of vehicle control group (P > 0.05) . In vitro chromosome aberration test, the rate of cells with chromosome aberration in 1 × 10 – 5 M lanthanum nitrate group significantly increased in the absence of S9 compared to that of the control group (χ2 = 12.109, P < 0.01); however, the proportion of cells with chromosome aberration was less than 5%, indicating a biological insignificance; in the presence of S9, there was no significant difference in chromosome aberration the between each lanthanum nitrate dose group and the control group (all P > 0.05). The results of Salmonella typhimurium strains bacterial reverse mutation test showed that there were no significant differences in the mutagenicity among lanthanum nitrate dose groups and the control group in both the presence and absence of S9 mixture. The results of teratogenic test showed that there were no significant differences in the growth and the implantation ability of pregnant rats among all dose groups and the vehicle group; lanthanum nitrate at concentration of 144 mg/kg BW inhibited fetal body weight and length significantly (both P < 0.05) and increased skeletal malformation of fetal rat compared with those of the vehicle group (χ2 = 9.939, P < 0.05). However, there was no significant difference in organ-specific and total visceral malformation among the dose groups (P > 0.05 for all). ConclusionsThe mutagenic effect of lanthanum nitrate was not observed under the conditions of this study and the study resulted in a no observable adverse effect level (NOAEL) of 36 mg/kg BW for lanthanum nitrate (15.38 mg/kg BW in terms of lanthanum).

The bacterial determinants that facilitate Mycobacterium tuberculosis (Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher the pressures facing the bacterium in vivo by assessing Mtb genes that are under positive selection in clinical isolates. One of the strongest targets of selection in the Mtb genome is lldD2, which encodes a quinone-dependent L-lactate dehydrogenase (LldD2) that catalyzes the oxidation of lactate to pyruvate. Lactate accumulation is a salient feature of the intracellular environment during infection and lldD2 is essential for Mtb growth in macrophages. We determined the extent of lldD2 variation across a set of global clinical isolates and defined how prevalent mutations modulate Mtb fitness. We show the stepwise nature of lldD2 evolution that occurs as a result of ongoing lldD2 selection in the background of ancestral lineage-defining mutations and demonstrate that the genetic evolution of lldD2 additively augments Mtb growth in lactate. Using quinone-dependent antibiotic susceptibility as a functional reporter, we also find that the evolved lldD2 mutations functionally increase the quinone-dependent activity of LldD2. Using 13C-lactate metabolic flux tracing, we find that lldD2 is necessary for robust incorporation of lactate into central carbon metabolism. In the absence of lldD2, label preferentially accumulates in dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) and is associated with a discernible growth defect, providing experimental evidence for accrued lactate toxicity via the deleterious buildup of sugar phosphates. The evolved lldD2 variants increase lactate incorporation to pyruvate while altering triose phosphate flux, suggesting both an anaplerotic and detoxification benefit to lldD2 evolution. We further show that the mycobacterial cell is transcriptionally sensitive to the changes associated with altered lldD2 activity which affect the expression of genes involved in cell wall lipid metabolism and the ESX- 1 virulence system. Together, these data illustrate a multifunctional role of LldD2 that provides context for the selective advantage of lldD2 mutations in adapting to host stress.

The Pacific white shrimp (Litopenaeus vannamei) is the most commercially-farmed shrimp species globally and is of significant ecological and economic importance. Here we report a high-quality genome assembly of L. vannamei using PacBio reads and Hi-C data. The assembly spans 1.87 Gb with scaffold N50 of 39.7 Mb and 87% of estimated genome size is assigned to 44 pseudochromosomes. The genome contains 24,861 protein-coding genes and a high proportion of transposable elements (64.33%). Significant expansion of gene families was observed in the genome related to locomotion, vision, and neural transmission, including via expansion of actin, myosin, rhodopsin, and neurotransmitter-gated ion-channel ligand binding domain genes, potentially revealing mechanisms underlying their evolved benthic adaptations. The genome assembly of L. vannamei provides valuable resources for future genetic research, breeding, and improvement of aquaculture traits, and will facilitate the research of genetic changes during evolution.

African swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use primary porcine alveolar macrophages to screen a kinase inhibitor library for anti-ASFV compounds. Six candidate compounds that inhibited ASFV infection with inhibition of > 90% were identified, among which brincidofovir exhibited optimal inhibitory effects on ASFV. Brincidofovir reduces ASFV replication in a dose-dependent manner (IC50 = 2.76 nM) without cytotoxicity (CC50 = 58 μM). It possesses the ability to reduce viral titres and inhibit viral structural protein expression. Time-of-addition assays suggest that the compound interferes with the post-invasion stage of the viral infection cycle. In pig challenge experiments, brincidofovir was indicated to protect pigs against ASFV-induced lethality by decreasing the viral load in organs and peripheral blood, while it alleviated the histopathological changes associated with ASFV infection. Furthermore, brincidofovir also decreased viral shedding in pigs with ASFV infection. Our data together demonstrate that brincidofovir may serve as a potentially effective agent for the prevention and control of ASFV infection, whereas further investigations are still required.

Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections.

Inverters are widely used in the military, industrial production and defense fields as current conversion devices that convert direct current to alternating current. If the inverter fails, it can cause damage to other equipment, resulting in financial losses and, in extreme cases, compromising the safety of users. In this study, by integrating neural networks, the input signals of inverters are quickly converted to Fourier spectrum amplitudes, and from fault signals (such as load phase voltage) to feature vectors. In order to realize automatic extraction and fault detection of inverters, an optimization method is used to determine the appropriate number of nodes in the hidden layer of complex neural networks. The ability to efficiently allocate limited computing, storage, and network resources to meet user demand for services; Continuously optimize quality of service (QoS), including reducing latency, improving bandwidth, and increasing reliability. These problems directly affect the performance and user experience of MEC systems. By studying these issues and proposing corresponding solutions, we aim to improve the performance of MEC systems and provide higher quality services. The accuracy of defect diagnosis can reach higher than 99%, and the method has a high remission rate, demonstrating its effectiveness and benefits.

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

ABSTRACT Strains of the Mycobacterium tuberculosis complex (MTBC) Beijing family aroused concern because they were often found in clusters and appeared to be exceptionally transmissible. However, it was later found that strains of the Beijing family were heterogeneous, and the transmission advantage was restricted to sublineage L2.3 or modern Beijing. In this study, we analyzed the previously published genome sequences of 7,896 L2.3 strains from 51 different countries. Using BEAST software to approximate the temporal emergence of L2.3, our calculations suggest that L2.3 initially emerged in northern East Asia during the early 15th century and subsequently diverged into six phylogenetic clades, identified as L2.3.1 through L2.3.6. Using terminal branch length and genomic clustering as proxies for transmissibility, we found that the six clades displayed distinct population dynamics, with the three recently emerged clades (L2.3.4 to L2.3.6) exhibiting significantly higher transmissibility than the older three clades (L2.3.1 to L2.3.3). Of the Beijing family strains isolated outside East Asia, 83.1% belonged to the clades L2.3.4 to L2.3.6, which were also associated with more cross-border transmission. This work reveals the heterogeneity in sublineage L2.3 and demonstrates that the global success of Beijing family strains is driven by the three recently emerged L2.3 clades. IMPORTANCE The recent population dynamics of the global tuberculosis epidemic are heavily shaped by Mycobacterium tuberculosis complex (MTBC) strains with enhanced transmissibility. The infamous Beijing family strain stands out because it has rapidly spread throughout the world. Identifying the strains responsible for the global expansion and tracing their evolution should help to understand the nature of high transmissibility and develop effective strategies to control transmission. In this study, we found that the L2.3 sublineage diversified into six phylogenetic clades (L2.3.1 to L2.3.6) with various transmission characteristics. Clades L2.3.4 to L2.3.6 exhibited significantly higher transmissibility than clades L2.3.1 to L2.3.3, which helps explain why more than 80% of Beijing family strains collected outside East Asia belong to these three clades. We conclude that the global success of L2.3 was not caused by the entire L2.3 sublineage but rather was due to the rapid expansion of L2.3.4 to L2.3.6. Tracking the transmission of L2.3.4 to L2.3.6 strains can help to formulate targeted TB prevention and control.

ABSTRACT Mixed infections of Mycobacterium tuberculosis, defined as the coexistence of multiple genetically distinct strains within a single host, have been associated with unfavorable treatment outcomes. Different methods have been used to detect mixed infections, but their performances have not been carefully evaluated. To compare the sensitivity of whole-genome sequencing (WGS) and variable-number tandem repeats (VNTR) typing to detect mixed infections, we prepared 10 artificial samples composed of DNA mixtures from two strains in different proportions and retrospectively collected 1,084 clinical isolates. The limit of detection (LOD) for the presence of a minor strain was 5% for both WGS and VNTR typing. The overall clinical detection rate of mixed infections was 3.7% (40/1,084) for the two methods combined, WGS identified 37/1,084 (3.4%), and VNTR typing identified 14/1,084 (1.3%), including 11 also identified by WGS. Multivariate analysis demonstrated that retreatment patients had a 2.7 times (95% confidence interval [CI], 1.2 to 6.0) higher risk of mixed infections than new cases. Collectively, WGS is a more reliable tool to identify mixed infections than VNTR typing, and mixed infections are more common in retreated patients. IMPORTANCE Mixed infections of M. tuberculosis have the potential to render treatment regimens ineffective and affect the transmission dynamics of the disease. VNTR typing, currently the most widely used method for the detection of mixed infections, detects mixed infections only by interrogating a small fraction of the M. tuberculosis genome, which necessarily limits sensitivity. With the introduction of WGS, it became possible to study the entire genome, but no quantitative comparison has yet been undertaken. Our systematic comparison of the ability of WGS and VNTR typing to detect mixed infections, using both artificial samples and clinical isolates, revealed the superior performance of WGS at a high sequencing depth (~100×) and found that mixed infections are more common in patients being retreated for tuberculosis (TB) in the populations studied. This provides valuable information for the application of WGS in the detection of mixed infections and the implications of mixed infections for tuberculosis control.

Community collaboration is a cornerstone of modern public health efforts. This work aimed to use community-engaged research to explore COVID-19 vaccination, testing, and infection in a minoritized community. This study was conducted in Miami, Florida, from March 2021 to February 2022 in community partner sites and the Miami Adult Studies on HIV (MASH) cohort. Sociodemographic characteristics, vaccination and testing beliefs, and COVID-19 challenges were self-reported. COVID-19 vaccinations were verified with medical records, testing history was self-reported, and severe acute respiratory syndrome coronavirus 2 positivity was determined via real-time reverse transcription–polymerase chain reaction (rt-PCR). Of 1689 participants, the median age was 57, 51% were male, 49% were non-Hispanic Black, 66% reported an income < USD 15,000/year, and 75.9% received at least one dose of a COVID-19 vaccine. Belief that COVID-19 vaccination is effective was associated with lower odds of COVID-19 positivity and was the strongest predictor of vaccination. Challenges accessing health care, housing, food, and transportation were associated with lower odds of vaccination. Employment, health insurance, higher education, and greater perceived test accuracy were associated with greater odds of COVID-19 testing. Social determinants of health and the belief that vaccines are effective and tests are accurate predicted behaviors and thus should be considered during public health crises in vulnerable communities.

Abstract Input saturation and disturbances often exist in hydraulic systems, reducing internal state stability and tracking response performances of the system as well as complicating the design of advanced non‐linear controllers. A practical method named active disturbance rejection controller is proposed by backstepping method for full‐state constrained hydraulic systems to constrain tracking errors in the desired boundaries and deal with input saturation as well as disturbances. To achieve the previously mentioned objectives, the disturbance compensation strategy and dynamic auxiliary systems are integrated into the barrier Lyapunov theory for the first time. It is proved that all states of hydraulic systems are kept within the ultimate boundaries with satisfactory dynamic performance and high steady‐state accuracy. In addition, when disturbances are constants, asymptotic tracking is theoretically achieved. The performance of the control strategy is verified by experimental results.

Abstract 2-Deoxyglucose (2-DG) can be used in antitumour research by inhibiting glycolysis and promoting the endoplasmic reticulum stress (ERS) pathway, but its clinical application is restricted due to dose-limiting side effects and survival chance for cancer cells by protective autophagy. Therefore, our research explored whether the combination of hydroxychloroquine (HCQ), an FDA-approved autophagy inhibiting drug, and 2-DG is a promising therapeutic strategy. Here, we report that HCQ combined with 2-DG can further inhibit the viability and migration and induce apoptosis of breast tumour cells compared with other individual drugs. The combination of 2-DG and HCQ can significantly reduce transplanted tumour size and tumour cell metastasis of the lung and liver in vivo. At the cellular level, HCQ suppressed autolysosome formation and terminated the autophagy process induced by 2-DG-mediated ERS, resulting in the continuous accumulation of misfolded proteins in the endoplasmic reticulum, which generated sustained ERS through the PERK-eIF2α-ATF-4-CHOP axis and triggered the transformation from a survival process to cell death. Our research reinforced the research interest of metabolic disruptors in triple-negative breast cancer and emphasized the potential of the combination of 2-DG and HCQ as an anticancerous treatment.

With the development of science and technology and the depletion of land resources, marine resources have been paid more and more attention gradually. Caulerpa lentillifera has been paid attention with high protein and dietary fiber. Caulerpa lentillifera is rich in nutrient, contains a variety of active substances, and has a variety of biological functions, such as immune regulation, anti-inflammation, anti-microbial, reducing blood sugar and blood lipids. It has a great potential medicinal value. In this paper, the latest studies on the components and functional characteristics of Caulerpa lentillifera are summarized, and it is found that the existing studies are mainly focus on nutrition, artificial culture and environmental application, but the exploration of the active components of Caulerpa lentillifera is not comprehensive. At present, scholars' research on phenols and flavonoids in Caulerpa lentillifera is only in the preliminary stage of content determination, and the extraction methods and active functions of polysaccharides and Caulerpin need to be further optimized and explored. In the future, in order to explore the drug potential of Caulerpa lentillifera, the active components of Caulerpa lentillifera should be deeply developed, the relationship between its structure and active function should be clarified, and its specific active function mechanism should be explored.

The high prevalence of the modern Beijing sublineage of Mycobacterium tuberculosis may be related to increased virulence, although the responsible mechanisms remain poorly understood. We previously described enhanced triacylglycerol accumulation in modern Beijing strains. Here we show that modern Beijing strains grow faster in vitro and trigger a vigorous immune response and pronounced macrophage infiltration. Transcriptomic analysis of bone marrow derived macrophages infected with modern Beijing lineage strains revealed a significant enrichment of infection, cholesterol homeostasis and amino acid metabolic pathways. The upregulation of proinflammatory / bactericidal cytokines was confirmed by RT-PCR analysis, which is also in consistent with the reduced bacterial burden in modern strains infected macrophages. These results suggest that modern Beijing strains elicit a hyperinflammatory response which might indicate a stronger virulence and contribute to their extensive global prevalence.

Abstract An asymptotic output feedback controller for the hydraulic systems with model uncertainty compensation and prescribed performance is proposed here, where state observers, funnel function and nonlinear adaptive controller are integrated via backstepping technology. Only position signal is available in the process of controller design, the velocity and load pressure are estimated by observers. And, the adaptive control law is carried out to approximate disturbance. Then, a funnel function is introduced to guarantee the prescribed tracking error performance and the potential singularity problem in prescribed performance control is avoided. Furthermore, the whole closed system is proved to be asymptotically stable using Lyapunov method. Comparative experimental results performed on hydraulic systems are studied to illustrate the effectiveness of the proposed controller.

Nighttime light data and land use data derived from remote sensing satellites are commonly used to monitor human activities on the Earth. A thorough understanding of the spatiotemporal interactions between these data enables better characterization and reconstruction of urbanization processes. In this work, a pixelwise fusion analysis using nighttime light data and land use data was performed to explore the spatiotemporal correlation between urban nighttime light luminosity transitions and land use changes. We found that the nighttime luminosity transitions are tightly related to the corresponding land use change types at the pixel level. A significant spatial correlation was identified between the nighttime light luminosity transitions and urban lands with intensive human activity. Relevant policies enacted in Beijing have greatly influenced the local light luminosity and land use type transitions. Pixels with change values in light luminosity in the same range have the same types of land use changes, the reasons for the changes in light luminosity are similar, and the spatial distribution characteristics are the same. This study provides a theoretical basis for quickly assessing changes in urban land use types through transitions in nighttime light luminosity. Simultaneously, the data in our study after integrating nighttime light luminosity and land use information perform well in urban development research and can provide valuable datasets and decision-making references for adjusting and optimizing urban sustainable development policies.

Abstract This paper investigates the potential impacts of dynamic wireless power transfer (DWPT) systems on the urban road network with a particular focus on charging and energy consumption implications. The paper is motivated by the recent advancement of connected and autonomous vehicle (CAV) technology and innovations on smart transportation infrastructure. An eco‐driving model aiming at energy consumption reduction is developed and a DWPT system layout suitable for charging eco‐driving CAVs at a signalised intersection is proposed. The idea is demonstrated in a simulated environment with different market penetration rate (MPR) of CAVs travelling through a signalized intersection equipped with the proposed DWPT system. The results suggest that as MPR of CAV increases, the energy savings for both CAVs and human‐driven vehicles (HVs) will increase significantly. At full MPR of CAVs, the reduction of average energy consumption of all types of vehicles can reach up to 62%. The average energy transferred and stored per battery electric vehicle can increase by up to 5% and 10%, respectively. These promising results indicate that a well‐designed DWPT system layout together with the eco‐driving behaviour of CAVs can have a positive impact on the urban transportation system in terms of resulting energy consumption and emissions.

In the face of the unrelenting global burden of tuberculosis (TB), antibiotics remain our most effective tools to save lives and control the spread of Mycobacterium tuberculosis (Mtb). However, we confront a dual challenge in our use of antibiotics: simplifying and shortening the TB drug regimen while also limiting the emergence and propagation of antibiotic resistance. This task is now more feasible due to the increasing availability of bacterial genomic data at or near the point of care. These resources create an opportunity to envision how integration of bacterial genetic determinants of antibiotic response into treatment algorithms might transform TB care. Historically, Mtb drug resistance studies focused on mutations in genes encoding antibiotic targets and the resulting increases in the minimal inhibitory concentrations (MICs) above a breakpoint value. But recent progress in elucidating the effects of functional genetic diversity in Mtb has revealed various genetic loci that are associated with drug phenotypes such as low-level MIC increases and tolerance which predict the development of resistance and treatment failure. As a result, we are now poised to advance precision medicine approaches in TB treatment. By incorporating information regarding Mtb genetic characteristics into the development of drug regimens, clinical care which tailors antibiotic treatment to maximize the likelihood of success has come into reach.

ABSTRACT There is growing evidence that genetic diversity in Mycobacterium tuberculosis, the causative agent of tuberculosis, contributes to the outcomes of infection and public health interventions, such as vaccination. Epidemiological studies suggest that among the phylogeographic lineages of M. tuberculosis, strains belonging to a sublineage of Lineage 2 (mL2) are associated with concerning clinical features, including hypervirulence, treatment failure, and vaccine escape. The global expansion and increasing prevalence of this sublineage has been attributed to the selective advantage conferred by these characteristics, yet confounding host and environmental factors make it difficult to identify the bacterial determinants driving these associations in human studies. Here, we developed a molecular barcoding strategy to facilitate high-throughput, experimental phenotyping of M. tuberculosis clinical isolates. This approach allowed us to characterize growth dynamics for a panel of genetically diverse M. tuberculosis strains during infection and after vaccination in the mouse model. We found that mL2 strains exhibit distinct growth dynamics in vivo and are resistant to the immune protection conferred by Bacillus Calmette-Guerin (BCG) vaccination. The latter finding corroborates epidemiological observations and demonstrates that mycobacterial features contribute to vaccine efficacy. To investigate the genetic and biological basis of mL2 strains’ distinctive phenotypes, we performed variant analysis, transcriptional studies, and genome-wide transposon sequencing. We identified functional genetic changes across multiple stress and host response pathways in a representative mL2 strain that are associated with variants in regulatory genes. These adaptive changes may underlie the distinct clinical characteristics and epidemiological success of this lineage. IMPORTANCE Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, is a remarkably heterogeneous disease, a feature that complicates clinical care and public health interventions. The contributions of pathogen genetic diversity to this heterogeneity are uncertain, in part due to the challenges of experimentally manipulating M. tuberculosis, a slow-growing, biosafety level 3 organism. To overcome these challenges, we applied a molecular barcoding strategy to a panel of M. tuberculosis clinical isolates. This novel application of barcoding permitted the high-throughput characterization of M. tuberculosis strain growth dynamics and vaccine resistance in the mouse model of infection. Integrating these results with genomic analyses, we uncover bacterial pathways that contribute to infection outcomes, suggesting targets for improved therapeutics and vaccines.

ABSTRACT Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented in Mycobacterium tuberculosis, their physiological roles remain elusive. We describe a TA system in M. tuberculosis which we named TacAT due to its homology to previously discovered systems in Salmonella. The toxin, TacT, blocks growth by acetylating glycyl-tRNAs and inhibiting translation. Its effects are reversed by the enzyme peptidyl tRNA hydrolase (Pth), which also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. Pth is essential in most bacteria and thereby has been proposed as a promising drug target for complex pathogens like M. tuberculosis. Transposon sequencing data suggest that the tacAT operon is nonessential for M. tuberculosis growth in vitro, and premature stop mutations in this TA system present in some clinical isolates suggest that it is also dispensable in vivo. We assessed whether TacT modulates pth essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacAT is disrupted. We show that pth essentiality is unaffected by the absence of tacAT. These results highlight a fundamental aspect of mycobacterial biology and indicate that Pth’s essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth’s potential as a viable target for new antibiotics. IMPORTANCE The global rise in antibiotic-resistant tuberculosis has prompted an urgent search for new drugs. Toxin-antitoxin (TA) systems allow bacteria to adapt rapidly to environmental changes, and Mycobacterium tuberculosis encodes more TA systems than any known pathogen. We have characterized a new TA system in M. tuberculosis: the toxin, TacT, acetylates charged tRNA to block protein synthesis. TacT's effects are reversed by the essential bacterial enzyme peptidyl tRNA hydrolase (Pth), which is currently being explored as an antibiotic target. Pth also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. We assessed whether TacT modulates pth essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacT is disrupted. We show that pth essentiality is unaffected by the absence of this TA system, indicating that Pth's essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth's potential as a viable target for new antibiotics.

Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.

The Visible Infrared Imaging Radiometer Suite Day/Night Band (VIIRS/DNB) nighttime light data is a powerful remote sensing data source. However, due to stray light pollution, there is a lack of VIIRS data in mid-high latitudes during the summer, resulting in the absence of high-precision spatiotemporal continuous datasets. In this paper, we first select nine-time series interpolation methods to interpolate the missing images. Second, we construct image pixel-level temporal continuity constraints and spatial correlation constraints and remove the pixels that do not meet the constraints, and the eliminated pixels are filled with the focal statistics tool. Finally, the accuracy of the time series interpolation method and the spatiotemporally constrained interpolation method (STCIM) proposed in this paper are evaluated from three aspects: the number of abnormal pixels (NP), the total light brightness value (TDN), and the absolute value of the difference (ADN). The results show that the images simulated by the STCIM are more accurate than the nine selected time series interpolation methods, and the image interpolation accuracy is significantly improved. Relevant research results have improved the quality of the VIIRS dataset, promoted the application research based on the VIIRS DNB long-time series night light remote sensing image, and enriched the night light remote sensing theory and method system.

The differences between the imaging environments of sensors lead to great differences in remote sensing images of the same area in different seasons. Relative radiation correction has high practical value as the main method to reduce such differences. However, the differences in vegetation radiation caused by seasonal changes are difficult to correct by traditional radiation correction methods. The corrected results also have difficulty achieving better results at the level of human eye visual perception. Moreover, the traditional measurement of the relative radiation correction result image quality index is not consistent with the human eye visual perception effect. To address the above two problems, this paper performs seasonal relative radiation correction on high-resolution remote sensing images by CycleGAN based on a convolutional neural network, including two transformations: 1) the transformation of remote sensing images from autumn-winter to spring-summer and 2) the transformation of remote sensing images from spring-summer to autumn-winter. The similarity between the relative radiation-corrected image and the reference image is measured by the convolutional neural network model with the ability to discriminate distances. The results show that the visual effect of this method is significantly better than that of other relative radiation correction methods, and the visual perception distance is consistent with the human eye visual perception judgment. The changed area still retains its original feature characteristics. The visual perception distance of the conversion from autumn-winter to spring-summer images is improved by 9% compared with other state-of-the-art methods. The visual perception distance of spring-summer images to autumn-winter images is improved by 3%. We expect that the method in this paper can be used for preprocessing to improve the accuracy of algorithms for remote sensing image classification, image change detection, etc.

Multi-channel signal has more abundant and accurate state characteristic information than single channel signal. How to separate fault characteristic information from the multi-channel signal is the key of fault diagnosis. As two typical multi-channel signal decomposition methods, multivariate empirical mode decomposition (MEMD) and multivariate variational mode decomposition (MVMD) are widely used in multi-channel signal analysis. However, MEMD and MVMD use cyclic iteration to complete the analysis of multi-channel signals, and it is difficult to overcome their inherent defects. In view of this, based on nonlinear sparse mode decomposition (NSMD), this paper proposes a multivariate nonlinear sparse mode decomposition (MNSMD) by constraining singular local linear operators to separate the natural oscillation modes in multi-channel signal. By constraining singular local linear operators into signal decomposition, MNSMD has obvious advantages in restraining mode aliasing and robustness. In addition, the local narrow-band component is used as the basis function for iteration, and the component signal is obtained by approaching the original signal. Through the simulation signal and gear fault signal analysis, the results show that, compared with MEMD and MVMD methods, MNSMD method can effectively complete gear fault diagnosis.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

E-mail is the main entry point for hackers to launch network attacks.Impersonating a trusted entity is an important means of e-mail forged.An attribute graph based on the e-mail authentication mechanism was built to measure the global adoption rate of e-mail security extension protocols for government agencies.Research on the deployment effect of security extension protocol was from three dimensions:e-mail content phishing,domain phishing,and letterhead phishing.The results show that about 70% of the SPF protocols are deployed in the mail systems of government agencies in various countries,and less than 30% of the DMARC protocol is deployed.The adoption rate of email identity detection is low.When forged e-mail gets in,the e-mail providers' warning mechanism for counterfeit emails need to be improved.

Abstract Background Ammonia is one of the most common toxicological environment factors affecting shrimp health. Although ammonia tolerance in shrimp is closely related to successful industrial production, few genetic studies of this trait are available. Results In this study, we constructed a high-density genetic map of the Pacific white shrimp (Litopenaeus vannamei) using specific length amplified fragment sequencing (SLAF-seq). The constructed genetic map contained 17,338 polymorphic markers spanning 44 linkage groups, with a total distance of 6360.12 centimorgans (cM) and an average distance of 0.37 cM. Using this genetic map, we identified a quantitative trait locus (QTL) that explained 7.41–8.46% of the phenotypic variance in L. vannamei survival time under acute ammonia stress. We then sequenced the transcriptomes of the most ammonia-tolerant and the most ammonia-sensitive individuals from each of four genetically distinct L. vannamei families. We found that 7546 genes were differentially expressed between the ammonia-tolerant and ammonia-sensitive individuals. Using QTL analysis and the transcriptomes, we identified one candidate gene (annotated as an ATP synthase g subunit) associated with ammonia tolerance. Conclusions In this study, we constructed a high-density genetic map of L. vannamei and identified a QTL for ammonia tolerance. By combining QTL and transcriptome analyses, we identified a candidate gene associated with ammonia tolerance. Our work provides the basis for future genetic studies focused on molecular marker-assisted selective breeding.

In this contribution, based-on the structurally confirmed pentacyanometallate (PPh4)2[Fe(CN)5(imidazole)]·(imidazole)·H2O (1) and the manganese compounds [Mn(L)(H2O)2]ClO4 (L = N,N-ethylenebis(3-methoxysalicylideneiminate) or [Mn(MAC)(H2O)Cl]ClO4 (MAC = 2,13-dimethyl-3,6,9,12,18-pentaazabicyclo-[12.3.1]octadeca-1(18),2,12,14,16- pentaene), two new cyanide-bridged bimetallic FeIII-MnIII/II complexes {[Mn(L)(H2O)]3[Fe(CN)5(imidazole)]}(ClO4) (2) and {[Mn(MAC)][Fe(CN)5(imidazole)]·CH3OH}n (3) were successfully synthesized and characterized by elemental analysis, IR spectroscopy and X-ray structure determination. Single X-ray diffraction analysis reveals the cationic FeMn3 tetranuclear entity for complex 2, which can be further assembled into supramolecular 1D ladder-like double chain by the strong intermolecular hydrogen bond interactions. For complex 3, it can be structurally characterized as neutral one-dimensional linear single infinite chain. The magnetic investigations discover the ferromagnetic coupling between the FeIII-MnIII units in complex 2 and the antiferromagnetic coupling in complex 3 between the FeIII-MnII units through the bridging cyanide group, respectively.

To characterize the cold tolerance mechanism of the Pacific white shrimp (Litopenaeus vannamei), we performed single-cell RNA sequencing (scRNA-seq) of ∼5185 hepatopancreas cells from cold-tolerant (Lv-T) and common (Lv-C) L. vannamei at preferred and low temperatures (28°C and 10°C, respectively). The cells fell into 10 clusters and 4 cell types: embryonic, resorptive, blister-like, and fibrillar. We identified differentially expressed genes between Lv-T and Lv-C, which were mainly associated with the terms “immune system,” “cytoskeleton,” “antioxidant system,” “digestive enzyme,” and “detoxification,” as well as the pathways “metabolic pathways of oxidative phosphorylation,” “metabolism of xenobiotics by cytochrome P450,” “chemical carcinogenesis,” “drug metabolism-cytochrome P450,” and “fatty acid metabolism.” Reconstruction of fibrillar cell trajectories showed that, under low temperature stress, hepatopancreas cells had two distinct fates, cell fate 1 and cell fate 2. Cell fate 1 was mainly involved in signal transduction and sensory organ development. Cell fate 2 was mainly involved in metabolic processes. This study preliminarily clarifies the molecular mechanisms underlying cold tolerance in L. vannamei, which will be useful for the breeding of shrimp with greater cold tolerance.

Pseudorabies virus (PRV) generally infects pigs and threatens the pig industry. However, recently we have isolated a PRV strain designated hSD-1/2019 from infected humans. In this study, we compared the complete genome sequence of hSD-1/2019 with those of pig-originated PRV strains. Sequence alignments revealed that the genome sequence of hSD-1/2019 was highly homologous to those of the porcine PRV strains. Phylogenetic analyses found that hSD-1/2019 was the closest related to porcine PRV endemic strains in China, particularly the variant strains circulating recently. We also showed that the glycoproteins important for the multiplication and pathogenesis of hSD-1/2019 were highly similar to those of the pig endemic strains. Diversifying selection analyses revealed that hSD-1/2019 and pig variant strains are under diversifying selection. Recombination analysis indicated that hSD-1/2019 was a recombinant of several PRV variant strains and an earlier PRV classic strain. Finally, we found that both human and pig-originated PRV strains could induce cytopathic effects in cells from humans, pigs, and mice, but only the human PRV and pig-variant PRV formed large syncytia in human cell lines. The data presented in this study contribute to our understanding of the molecular basis for the pathogenesis of human PRV from a genomic aspect.

The N6-methyladenosine (m6A) is the most abundant internal modification in advanced eukaryotic mRNAs, and it plays an important role in mRNA metabolism and diverse biological processes. Moreover, m6A modification is dynamically reversible and may reshape gene expression patterns after demethylation induced by drug interventions, which may reverse the occurrence and progression of certain diseases. Although the role of changes in DNA methylation in ophthalmic diseases has been well described, the regulatory role of the m6A modification in ophthalmic diseases is still a new field of study. This paper aims to systematically summarize the latest research progress about m6a-modification-related ophthalmic diseases and potential therapeutic strategies. All English literature relevant to our research was searched in PubMed and CNKI databases, using appropriate keywords. Our study reviews the regulatory role of m6A in ophthalmic diseases. It covers almost all of the reported m6A-related ophthalmic diseases and proposes potential treatment strategies for each disease. This review will provide direction for further research on m6A in ophthalmic diseases and help in the treatment of ophthalmic diseases in the future.

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up‐regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non‐small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain‐ and loss‐of‐function studies revealed that LINC01436 acted as a proto‐oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)‐30a‐3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia‐sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Abstract Background Rapid and sensitive detection of H2O2 especially endogenous H2O2 is of great importance for series of industries including disease diagnosis and therapy. In this work, uniform FePt nanoparticles are successfully anchored onto Few-layer molybdenum disulfide nanosheets (F-MoS2 NSs). The powder X-ray diffraction, transmission electron microscopy, UV–Vis spectra and atomic force microscopy were employed to confirm the structure of the obtained nanocomposites (F-MoS2-FePt NCs). The prepared nanocomposites show efficient peroxidase-like catalytic activities verified by catalyzing the peroxidation substrate 4,4′-diamino-3,3′,5,5′-tetramethylbiphenyl (TMB) with the existence of H2O2. Results The optimal conditions of the constructed colorimetric sensing platform is proved as 35 °C and pH 4.2. Under optimal catalytic conditions, the detection limit for H2O2 detection reaches 2.24 μM and the linear ranger is 8 μM to 300 μM. Furthermore, the proposed colorimetric sensing platform was successfully utilized to detect the intracellular H2O2 of cancer cells (MCF-7). Conclusions These findings indicated that the F-MoS2-FePt-TMB-H2O2 system provides a potential sensing platform for hydrogen peroxide monitoring in living cells.

In this paper, a state constraint controller with disturbance compensation is proposed for uncertain nonlinear systems to improve the control performance without violating the full state constraints. A series of extended state observers are designed to estimate disturbances that include the unmodeled dynamics and the modeling errors. To guarantee non-violation of state constraints while compensating the disturbances, based on the backstepping technique, the state constraint controller with extended state observer is proposed by using the barrier Lyapunov function. Then, the stability of the closed-loop system is proved theoretically. Moreover, exponentially asymptotic tracking is achieved when the disturbances are not time-variant. Finally, the effectiveness of the proposed approach is verified by two examples.

Effective condition monitoring provides some benefits such as improving safety and reliability. Roller bearing is the key component of rotating machinery, and a novel roller bearing condition monitoring method based on rational Hermite interpolation-local characteristic-scale decomposition (RHLCD) and fusion variable predictive model-based class discriminate method (FVPMCD) is proposed in this paper. RHLCD can adaptively decompose any complex signal into a sum of rational intrinsic scale components (RISCs), whose instantaneous frequency has physical meaning. In addition, targeting the limitation of variable predictive model-based class discriminate method (VPMCD), FVPMCD is presented. First, four kinds of common models are used to recognize a sample. Then, the recognition results of each model are satisfied, and the recognition probability of each state is calculated. Finally, the largest recognition probability of the state is chosen to recognize categories. The analytical results of experimental signals indicate that the proposed condition monitoring approach can identify the states of roller bearing effectively.

Pseudorabies virus (PRV) can infect most mammals and is well known for causing substantial economic losses in the pig industry. In addition to pigs, PRV infection usually leads to severe itching, central nervous system dysfunction, and 100% mortality in its non-natural hosts. It should be noted that increasing human cases of PRV infection have been reported in China since 2017, and these patients have generally suffered from nervous system damage and even death. Here, we reviewed the current prevalence and variation in PRV worldwide as well as the PRV-caused infections in animals and humans, and briefly summarized the vaccines and diagnostic methods used for pseudorabies control. Most countries, including China, have control programs in place for pseudorabies in domestic pigs, and thus, the disease is on the decline; however, PRV is still globally epizootic and an important pathogen for pigs. In countries where pseudorabies in domestic pigs have already been eliminated, the risk of PRV transmission by infected wild animals should be estimated and prevented. As a member of the alphaherpesviruses, PRV showed protein-coding variation that was relatively higher than that of herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV), and its evolution was mainly contributed to by the frequent recombination observed between different genotypes or within the clade. Recombination events have promoted the generation of new variants, such as the variant strains resulting in the outbreak of pseudorabies in pigs in China, 2011. There have been 25 cases of PRV infections in humans reported in China since 2017, and they were considered to be infected by PRV variant strains. Although PRV infections have been sporadically reported in humans, their causal association remains to be determined. This review provided the latest epidemiological information on PRV for the better understanding, prevention, and treatment of pseudorabies.

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.

An isogeometric analysis (IGA) method is proposed for investigating the active shape and vibration control of functionally graded plates (FGPs) with surface-bonded piezoelectric materials in a thermal environment. A simple first-order shear deformation theory (S-FSDT) with four variables is used to describe the displacement field of the plates. To ensure the investigation of smart piezoelectric structure in the thermal environment closer to the actual situation, a modified piezoelectric constitutive equation with consideration of the temperature effect of dielectric and piezoelectric strain coefficients is implemented to replace the traditional linear piezoelectric constitutive equation. Meanwhile, the neutral surface is adopted to avoid the stretching-bending coupling. The accuracy and effectiveness of the proposed S-FSDT-based IGA method are verified by comparing with several existing numerical examples. Then, the static bending and open-loop control of the plates under mechanical and thermal loads are further studied. Finally, the active control including static bending control and vibration control of piezoelectric functionally graded plates (PFGPs) is also investigated by using a displacement-velocity feedback control law.

Genomic dissection of antibiotic resistance in bacterial pathogens has largely focused on genetic changes conferring growth above a single critical concentration of drug. However, reduced susceptibility to antibiotics-even below this breakpoint-is associated with poor treatment outcomes in the clinic, including in tuberculosis. Clinical strains of Mycobacterium tuberculosis exhibit extensive quantitative variation in antibiotic susceptibility but the genetic basis behind this spectrum of drug susceptibility remains ill-defined. Through a genome wide association study, we show that non-synonymous mutations in dnaA, which encodes an essential and highly conserved regulator of DNA replication, are associated with drug resistance in clinical M. tuberculosis strains. We demonstrate that these dnaA mutations specifically enhance M. tuberculosis survival during isoniazid treatment via reduced expression of katG, the activator of isoniazid. To identify DnaA interactors relevant to this phenotype, we perform the first genome-wide biochemical mapping of DnaA binding sites in mycobacteria which reveals a DnaA interaction site that is the target of recurrent mutation in clinical strains. Reconstructing clinically prevalent mutations in this DnaA interaction site reproduces the phenotypes of dnaA mutants, suggesting that clinical strains of M. tuberculosis have evolved mutations in a previously uncharacterized DnaA pathway that quantitatively increases resistance to the key first-line antibiotic isoniazid. Discovering genetic mechanisms that reduce drug susceptibility and support the evolution of high-level drug resistance will guide development of biomarkers capable of prospectively identifying patients at risk of treatment failure in the clinic.

Nitrite is a major environmental toxin in aquaculture systems that disrupts multiple physiological functions in aquatic animals. Although nitrite tolerance in shrimp is closely related to successful industrial production, few genetic studies of this trait are available. In this study, we constructed a high-density genetic map of Litopenaeus vannamei with 17,242 single nucleotide polymorphism markers spanning 6,828.06 centimorgans (cM), with an average distance of 0.4 cM between adjacent markers on 44 linkage groups (LGs). Using this genetic map, we identified two markers associated with nitrite tolerance. We then sequenced the transcriptomes of the most nitrite-tolerant and nitrite-sensitive individuals from each of four genetically distinct L. vannamei families (LV-I–4). We found 2,002, 1,983, 1,954, and 1,867 differentially expressed genes in families LV-1, LV-2, LV-3, and LV-4, respectively. By integrating QTL and transcriptomics analyses, we identified a candidate gene associated with nitrite tolerance. This gene was annotated as solute carrier family 26 member 6 (SLC26A6). RNA interference (RNAi) analysis demonstrated that SLC26A6 was critical for nitrite tolerance in L. vannamei. The present study increases our understanding of the molecular mechanisms underlying nitrite tolerance in shrimp and provides a basis for molecular-marker-assisted shrimp breeding.