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Little is known about the comprehensive factors influencing temporal changes in microplastic abundance in marine ecosystems. We investigated seasonal variations in the microplastic distribution in marine sediments in multiple-used zones of Eastern Guangdong in the South China Sea. The top 10 cm sediments from 26 sites were collected by grab sampling in the spring, summer, and winter of 2021. Marine sediments had the lowest microplastic abundance in summer, significantly lower than in other seasons. The size of microplastics varied from 22.5 to 4363.3 µm but the 50–200 µm range was the most abundant. Transparent and fragmented microplastics were the most frequently observed composition. Microplastic abundance negatively correlated to distance to the coast. However, seaweed ecosystems impacted microplastic abundance by changing the microenvironment and/or direct contact and entrapment. Microplastic abundance is closely related to coastal mariculture and local residential and industrial activities. Polypropylene, polypropylene-polyethylene copolymer, polyethylene terephthalate, and polyethylene were the most frequently detected compositions, probably from packaging materials, textiles, and electronic/electrical/building industries. This work helps to understand the role of multiple-used zones and their influence on microplastic distributions in marine ecosystems. Appropriate management of the use and disposal of plastic waste on land was recommended to alleviate microplastic pollution in the marine environment.

Beibu Gulf’s (BBG) Indo-Pacific humpback dolphins present both a genetic differentiation and phenotypical differences from conspecifics from other areas of the South China Sea. Given the recent urbanization and industrialization in southern China, humpback dolphins from the BBG warrant conservation attention. However, this population’s demographic trend is unclear, making it hard to take conservation measures. To assess the population status of humpback dolphins in the BBG, photo-identification surveys were conducted between 2015 and 2019 in the inshore region surrounding the Dafeng River Estuary, which represents the most urbanized and industrialized coastal area of the BBG region. Robust design modeling suggested a constant survival for the female adults (0.89, 95% CI: 0.83–0.94). In comparison, the survival of the juvenile and sex-undetermined adults dropped from 0.92 (95% CI: 0.75–0.98) in 2015 to 0.86 (95% CI: 0.71–0.94) in 2016 and bounced back to 0.89 (95% CI: 0.80–0.94) in 2018. The low level of survival may justify the rapid decline in the annual population size from 156 (95% CI: 133–184) in 2015 to 102 (95% CI: 98–107) in 2019. We found little impact of emigration on the dolphin demographic process. Instead, the low and fluctuating survivals, although with overlapping confidence intervals, seemingly suggested a presence of strong marine stressor(s). Our study highlighted that obtaining high-resolution data is essential to improving our understanding of the demographic dynamics. Moreover, the anthropogenic stress in the BBG region should be quantitatively studied in both temporal and spatial perspectives, to help depict the ecological response of the dolphins to anthropogenic activities.

Pregnancy complicated with hereditary haemorrhagic telangiectasia (HHT) is a rare condition. This case report presents an extremely rare case with the co-occurrence of HHT and congenital heart disease. In this report, a 43-year-old woman at 36 + 4 weeks of gestation experienced haemoptysis with a volume of approximately 300 ml for the first time. Uncommonly, her transthoracic echocardiogram revealed a previously unrecognized atrial septal defect (ASD) and pulmonary hypertension (PH) for the first time at 36 + 1 weeks of gestation. Chest computed tomography revealed an arteriovenous malformation (AVM) in the right lower lobe of the lung. Due to concerns of rebleeding of ruptured pulmonary arteriovenous malformations (PAVMs), the patient underwent a caesarean section at 36 + 6 weeks of gestation. A healthy male infant weighing 2800 g was delivered. To the best of our knowledge, there have been few reports about HHT with ASDs and PH during advanced pregnancy. This current case report highlights the necessity for clinicians to pay considerable attention to cardiac structural abnormalities, which can worsen PAVM in patients with HHT during pregnancy, for whom terminating the pregnancy in time may reduce the risk of PAVM rupture.

Background and PurposeGastrointestinal hemorrhage (GIH) is associated with a poorer prognosis and a higher mortality rate after acute ischemic stroke (AIS), but its association with outcomes after endovascular treatment (EVT) remains unclear. This study aimed to assess the incidence, risk factors, and relationships among clinical outcomes of GIH after EVT in patients with acute basilar artery occlusion (BAO).MethodsConsecutive patients treated with EVT were identified from the EVT for Acute Basilar Artery Occlusion Study (BASILAR) registry. All enrolled patients were divided into GIH and non-GIH subgroups, and the independent predictors of GIH after EVT were explored. An ordinal logistic regression model was used to assess the association between GIH and primary outcome [distribution of modified Rankin scale (mRS)] at 90 days, while binary logistic regression models for other outcomes were also employed.ResultsAmong 647 patients with acute BAO, 114 (17.6%) patients experienced GIH after EVT. Higher glucose levels at admission, longer procedure time, and general anesthesia were the independent predictors of GIH after EVT, while protective factors include the posterior circulation-Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) ≥ 5 and a history of hyperlipidemia. Compared with the non-GIH group, the GIH group was associated with a worse functional outcome [adjusted common odds ratio (OR), 2.12 (95% CI, 1.39–3.25)], lower rates of functional independence [adjusted OR,.47 (95% CI, 0.26–0.88)], a favorable outcome [adjusted OR, 0.41 (95% CI, 0.22–0.73)], and a higher risk of 90-day mortality [adjusted OR, 1.76 (95% CI, 1.08–2.85)].ConclusionThis study concluded that GIH is not uncommon after EVT in patients with acute BAO and is associated with worse functional disability and higher mortality.

The deterioration of rock strength due to cyclic fluctuations in the groundwater level in drawdown regions influences bank slope stability. Based on wetting–drying cycling and uniaxial compression tests of sandstone specimens, the intact rock strength deterioration characteristics were analyzed. Considering different types of rock mass discontinuities, the rock mass strength deterioration features were shown. The results of rock mass strength deterioration characteristics were then applied in sandstone slope stability analysis. Using the finite element method, the safety factors of the slope under different wetting–drying cycles were computed based on the generalized Hoek–Brown failure criterion. Meanwhile, statistical distribution features of strength parameters were considered, and safety factor distribution of studied slopes was obtained with Monte Carlo simulation. The results show that rock mass deformation modulus decreased during wetting–drying cycling. The mean safety factors of the slope with any type of discontinuities were reduced by wetting–drying cycling in probabilistic analyses. Wetting–drying cycling plays an important role in damaging slope stability at initial stages since the degree of rock mass strength deterioration is remarkable during initial wetting–drying cycles. However, the rock mass strength and safety factor of the slope are reduced gently after 10 wetting–drying cycles. This research presents the phases of the effect of wetting–drying cycles on sandstone slope stability in drawdown regions.

Abstract Background Primary dysmenorrhea (PD) is a leading cause of dysmenorrhea among adolescent girls. Manual acupuncture may be considered as an effective treatment for PD, but high-quality evidence remains limited. This trial aims to evaluate the efficacy and safety of acupuncture for the prevention of PD as compared with sham acupuncture and usual care. Methods/design This is a three-arm, randomized, controlled clinical trial in which the patients, assessors, and statisticians will be blinded. A total of 300 acupuncture-naive patients who were diagnosed as PD will be randomly allocated to the verum acupuncture, sham acupuncture, or usual care groups in a 2:2:1 ratio. Patients in the verum acupuncture group will receive manual acupuncture at specific acupuncture points with penetrating needling, while those in the sham acupuncture group will receive non-penetrating needling at non-acupuncture points. They will be given five sessions over a menstrual cycle for 3 menstrual cycles. Patients in the usual care group will receive health education and informed to receive manual acupuncture for free after waiting for 7 menstrual cycles. The primary outcome will be the change from baseline in the Cox Menstrual Symptom Scale Score (CMSS). The secondary outcomes will be the changes in Massachusetts General Hospital Acupuncture Sensation Scale (MASS), visual analog scale (VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI- II), Acupuncture Expectancy Scale (AES), 60-item NEO Personality Inventory-Short Form (NEO-FFI), and acute medication intake. The adverse events will be recorded at every visit. The analyses will be performed base on a full analysis set (FAS) and a per-protocol set (PPS). Discussion This study may provide high-quality evidence regarding the efficacy and safety of manual acupuncture for PD. In addition, the results of this study will help to identify the efficacy of acupuncture due to the specific effects of acupuncture or placebo effects of acupuncture ritual. Trial registration Clinical Trials.gov NCT02783534 . Registered on 26 May 2016

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming changes and underlying molecular mechanisms in TOF-related chronic myocardial hypoxia damage are still unclear.Methods: In this study, we combined microarray transcriptomics analysis with liquid chromatography tandem-mass spectrometry (LC–MS/MS) spectrum metabolomics analysis to establish the metabolic reprogramming that occurs in response to chronic hypoxia damage. Two Gene Expression Omnibus (GEO) datasets, GSE132176 and GSE141955, were downloaded to analyze the metabolic pathway in TOF. Then, a metabolomics analysis of the clinical samples (right atrial tissue and plasma) was performed. Additionally, an association analysis between differential metabolites and clinical phenotypes was performed. Next, four key genes related to sphingomyelin metabolism were screened and their expression was validated by real-time quantitative PCR (QT-PCR).Results: The gene set enrichment analysis (GSEA) showed that sphingolipid metabolism was downregulated in TOF and the metabolomics analysis showed that multiple sphingolipids were dysregulated. Additionally, genes related to sphingomyelin metabolism were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase (UGCG), Sphingosine-1-Phosphate Phosphatase 2 (SGPP2), Fatty Acid 2-Hydroxylase (FA2H), and Sphingosine-1-Phosphate Phosphatase 1 (SGPP1), were downregulated in TOF.Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.

Clostridium perfringens (C. perfringens) is one of the foremost pathogens responsible for diarrhea in foals. As antibiotic resistance increases, phages that specifically lyse bacteria are of great interest to us with regard to C. perfringens. In this study, a novel C. perfringens phage DCp1 was isolated from the sewage of a donkey farm. Phage DCp1 had a non-contractile short tail (40 nm in length) and a regular icosahedral head (46 nm in diameter). Whole-genome sequencing indicated that phage DCp1 had a linear double-stranded DNA genome with a total length of 18,555 bp and a G + C content of 28.2%. A total of 25 ORFs were identified in the genome, 6 of which had been assigned to functional genes, others were annotated to encode hypothetical proteins. The genome of phage DCp1 lacked any tRNA, virulence gene, drug resistance gene, or lysogenic gene. Phylogenetic analysis indicated that phage DCp1 belonged to the family Guelinviridae, Susfortunavirus. Biofilm assay showed that phage DCp1 was effective in inhibiting the formation of C. perfringens D22 biofilms. Phage DCp1 could completely degrade the biofilm after 5 h of interaction. The current study provides some basic information for further research on phage DCp1 and its application.

With the development of intelligent transportation,it has become an urgent problem to quickly and accurately recognize complex traffic scene.In recent years,a large number of scene recognition methods have been proposed to improve the effectiveness of traffic scene recognition,however,most of these algorithms cannot extract the semantic characteristics of the concept of vision,leading to the low recognition accuracy in traffic scenes.Therefore,a novel traffic scene recognition algorithm which extracts the high-level semantic and structural information for improving the accuracy was proposed.A system to discover semantically meaningful descriptions of the scene classes to reduce the “semantic gap” between the high level and the low-level feature representation was built.Then,the multi-label network was trained by minimizing loss function (namely,element-wise logistic loss) to obtain the high-level semantic representation of traffic scene images.Finally,experiments on four large-scale scene recognition datasets show that the proposed algorithm considerably outperforms other state-of-the-art methods.

Summary: Selective identification of newly synthesized proteins is challenging because all proteins, both existing and nascent, have the same amino acid pool and are therefore chemically indistinguishable. L-homopropargylglycine is an amino acid analog of methionine containing an alkyne moiety that can undergo a classic click chemical reaction with azide containing Alexa Fluor. Here, we present an integrated tool based on immunofluorescence staining to accurately trace and localize the newly synthesized protein in isolated primary mouse hepatocytes.For complete details on the use and execution of this protocol, please refer to Shen et al. (2021).

Background: Low vitamin D (VitD) status is becoming a global health issue. Previous heterogenous results are urging a meta-analysis to delineate a panorama of VitD conditions in the general population in Mainland of China. Methods: We performed a systematic review and meta-analysis by searching PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, WanFang, and VIP databases up to June 4, 2021. The inclusion criteria were as follows: (1) original articles or dissertations focused on VitD status of people in Mainland of China; and (2) studies were population-based, cross-sectional, or longitudinal cohort with baseline data. The outcomes were serum 25(OH)D concentration and the prevalence of low VitD status. Low VitD status included VitD deficiency (

A novel virulent bacteriophage vB_EcoM_swi3 (swi3), isolated from swine feces, lyzed 9% (6/65) of Escherichia coli and isolates 54% (39/72) of Salmonella enteritidis isolates, which were all clinically pathogenic multidrug-resistant strains. Morphological observation showed that phage swi3 belonged to the Myoviridae family with an icosahedral head (80 nm in diameter) and a contractile sheathed tail (120 nm in length). At the optimal multiplicity of infection of 1, the one-step growth analysis of swi3 showed a 25-min latent period with a burst size of 25-plaque-forming units (PFU)/infected cell. Phage swi3 remained stable both at pH 6.0–8.0 and at less than 50°C for at least 1 h. Genomic sequencing and bioinformatics analysis based on genomic sequences and the terminase large subunit showed that phage swi3 was a novel member that was most closely related to Salmonella phages and belonged to the Rosemountvirus genus. Phage swi3 harbored a 52-kb double-stranded DNA genome with 46.02% GC content. Seventy-two potential open reading frames were identified and annotated, only 15 of which had been assigned to functional genes. No gene associated with pathogenicity and virulence was identified. The effects of phage swi3 in treating pathologic E. coli infections in vivo were evaluated using a mouse model. The administration of a single intraperitoneal injection of swi3 (106 PFU) at 2 h after challenge with the E. coli strain (serotype K88) (108 colony-forming units) sufficiently protected all mice without toxic side effects. This finding highlighted that phage swi3 might be used as an effective antibacterial agent to prevent E. coli and S. enteritidis infection.

Background: Acute kidney injury (AKI) is a common and serious complication faced by children following ventricular septal defect (VSD) surgery with cardiopulmonary bypass (CPB). The objective of this study was to explore potential predictors inherent to AKI.Methods: VSD infants who were scheduled for elective cardiac surgery with CPB from 2017 to 2020 were enrolled in this study. Based on the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria, patients were divided into AKI and non-AKI groups. Univariate and multivariate logistic regression analyses were carried out in order to evaluate potential risk factors for AKI. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive probabilities of risk factors for AKI.Results: Of all the 338 enrolled VSD infants, 49 manifested AKI with an incidence of 14.5% (49/338). The ROC curve indicated that albumin-to-fibrinogen ratio (AFR) during CPB was a significant predictor of AKI [area under the curve (AUC), 0.711; p < 0.001]. Based on the univariate and multivariate logistic analyses, AFR during CPB [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.22–2.76, p = 0.011] was the only independent risk factor for AKI.Conclusions: This study demonstrated that a low AFR (

A novel bacteriophage vB_SauS_SA2 (hereafter designated SA2) that infects Staphylococcus aureus was isolated. At a multiplicity of infection (MOI) of 0.1, phage SA2 had a latent period of about 10 min with a burst size of 293 PFUs/infected cell (PFU, plaque forming unit). Phage SA2 had a double-stranded DNA genome with a length of 89,055 bp and a G + C content of 31.9%. The genome contained 130 open reading frames (ORFs), 28 of which had assigned functions, and 18 were unique. One tRNA gene (tRNAAsn) was discovered, and no virulence genes were identified. Its genome showed very low similarity with phage genomes deposited in public databases (75% nucleotide identity and 7% query coverage). The unique characteristics of phage SA2 led to the proposal of a new Siphoviridae genus named ‘SA2likevirus’.

Abstract Human–wildlife conflict (HWC) has become a conservation focus for both protected area management and local communities in many parts of the world. The incidence and mediation of HWCs are rooted in coupled environmental and socioeconomic contexts. A systematic analysis of HWCs was undertaken in 2016 in the Wolong Nature Reserve located in Sichuan Province, southwestern China. Semi‐structured interviews were conducted with 201 local households to understand the occurrence of wildlife damage, the wildlife species involved, the typical losses incurred, and the mitigation measures employed. The results revealed that local HWC has increased rapidly in recent years due to effective biodiversity conservation and ecological restoration policies. Despite the widespread occurrence of HWCs, with nearly all respondents stating that they had suffered a financial loss, appropriate compensation schemes are lacking. Local respondents' expected compensation amount and style were investigated, and it was concluded that integrated compensation and community development plans are needed to mediate and resolve HWC. In particular, greater attention should be given to reduce local households' dependence on agriculture and transform local livelihood strategies to alternative economic activities not related to farming, such as ecotourism development and migrating employment.

Scene classification is increasingly popular due to its extensive usage in many real-world applications such as object detection, image retrieval, and so on. Traditionally, the low-level hand-crafted image representations are adopted to describe the scene images. However, they usually fail to detect semantic features of visual concepts, especially in handling complex scenes. In this paper, we propose a novel high-level image representation which utilizes image attributes as features for scene classification. More specifically, the attributes of each image are firstly extracted by a deep convolution neural network (CNN), which is trained to be a multi-label classifier by minimizing an element-wise logistic loss function. The process of generating attributes can reduce the “semantic gap” between the low-level feature representation and the high level scene meaning. Based on the attributes, we then build a system to discover semantically meaningful descriptions of the scene classes. Extensive experiments on four large-scale scene classification datasets show that our proposed algorithm considerably outperforms other state-of-the-art methods.

Compressor thermodynamics under varying capacity loads are difficult to predict due to the interaction between the valve-sealing element motion, unloader behavior, and fluid flow. In this paper, a new comprehensive mathematical model of piston compressor under various gas flow loads is established, which is combined with a reciprocating compressor, intake valves, hydraulic plunger cylinder, and unloader, and the model is validated by experimental data. Results show that the installation of finger-type unloaders clearly leads to an increase in flow loss. With a reduction in the flow load of compressed gas, the closing impact velocity of the suction valve plate increases, and the valve appears to oscillate under capacity regulation conditions, leading to premature fatigue damage of the valve component. The optimal combination of design parameters for a suction valve in the capacity regulation system is a 2.7 mm valve lift with a 2100 N/m spring stiffness, yielding a minimum valve resistance loss within admissible valve dynamic motion. The reset spring stiffness of 20 kN/m is chosen as the optimal parameter value by which the impact speed of the suction valve plate at the valve seat is clearly reduced, avoiding excessive impact stress in the reset process.

The gut microbiome is a unique marker for cetaceans’ health status, and the microbiome composition of their skin wounds can indicate a potential infection from their habitat. Our study provides the first comparative analysis of the microbial communities from gut regions and skin wounds of an individual Indo-Pacific finless porpoise (Neophocaena phocaenoides). Microbial richness increased from the foregut to the hindgut with variation in the composition of microbes. Fusobacteria (67.51% ± 5.10%), Firmicutes (22.00% ± 2.60%), and Proteobacteria (10.47% ± 5.49%) were the dominant phyla in the gastrointestinal tract, while Proteobacteria (76.11% ± 0.54%), Firmicutes (22.00% ± 2.60%), and Bacteroidetes (10.13% ± 0.49%) were the dominant phyla in the skin wounds. The genera Photobacterium, Actinobacillus, Vibrio, Erysipelothrix, Tenacibaculum, and Psychrobacter, considered potential pathogens for mammals, were identified in the gut and skin wounds of the stranded Indo-Pacific finless porpoise. A comparison of the gut microbiome in the Indo-Pacific finless porpoise and other cetaceans revealed a possible species-specific gut microbiome in the Indo-Pacific finless porpoise. There was a significant difference between the skin wound microbiomes in terrestrial and marine mammals, probably due to habitat-specific differences. Our results show potential species specificity in the microbiome structure and a potential threat posed by environmental pathogens to cetaceans.

Microsatellites are one of the important genome characterizations that can be a valuable resource for variety identification, genetic diversity, phylogenetic analysis, as well as comparative and conservation genomics research. Here, we developed comprehensive microsatellites through genome-wide mining for the threatened cetacean Indo-Pacific humpback dolphin (Sousa chinensis). We found 87,757 microsatellites with 2–6 bp nucleotide motifs, showing that about 32.5 microsatellites per megabase comprises microsatellites sequences. Approximately 97.8% of the markers developed in this study were consistent with the published identified markers. About 75.3% microsatellites were with dinucleotide motifs, followed by tetranucleotide motifs (17.4%), sharing the same composition pattern as other cetaceans. The microsatellites were not evenly distributed in the S. chinensis genome, mainly in non-coding regions, with only about 0.5% of the markers located in coding regions. The microsatellite-containing genes were mainly functionally enriched in the methylation process, probably demonstrating the potential impacts of microsatellites on biological functions. Polymorphic microsatellites were developed between different genders of S. chinensis, which was expected to lay the foundation for genetic diversity investigation in cetaceans. The specific markers for a male Indo-Pacific humpback dolphin will provide comprehensive and representative male candidate markers for sex identification, providing a potential biomolecular tool for further analysis of population structure and social behavior of wild populations, population trend evaluation, and species conservation management.

Abstract Background Mud crabs, Scylla spp., are commercially important large-size marine crustaceans in the Indo-West Pacific region. As females have the higher growth rate and economic value, the production of all female stocks is extremely essential in aquaculture. However, the sex determination mechanism is still unclear. Development of sex-specific genetic markers based on next-generation sequencing proved to be an effective tool for discovering sex determination system in various animals. Results Restriction-site associated DNA sequencing (RAD-seq) was employed to isolate sex-specific SNP markers for S. paramamosain. A total of 335.6 million raw reads were obtained from 20 individuals, of which 204.7 million were from 10 females and 130.9 million from 10 males. After sequence assembly and female-male comparison, 20 SNP markers were identified to be sex-specific. Furthermore, ten SNPs in a short sequence (285 bp) were confirmed heterozygous in females and homozygous in males in a large population by PCR amplification and sequencing. Subsequently, a female-specific primer was successfully designed according to the female-specific nucleotide which could amplify an expected band from females but not from males. Thus, a rapid and effective method for molecular sexing in S. paramamosain was developed, meanwhile, this method could successfully identify the sex of S. tranquebarica and S. serrata. Finally, nine and four female-specific SNP markers were detected in S. tranquebarica and S. serrata, respectively. Conclusions Sex-specific SNP markers were firstly identified in crab species and showed female heterogamety and male homogamety, which provided strong genetic evidence for a WZ/ZZ sex determination system in mud crabs S. paramamosain, S. tranquebarica and S. serrata. These findings will lay a solid foundation for the study of sex determination mechanism, sex chromosome evolution, and the development of mono-sex population in crustaceans.

The novel virulent Siphoviridae bacteriophage swi2 was isolated from a pig farm, and its biological characteristics, genome architecture, and infection-related properties were characterized. Phage swi2 has a high titer of 1.01 × 1012 PFU/mL with good tolerance to UV rays and remains stable in the pH range of 6–10 and at temperatures less than 50°C. One-step growth analysis revealed that phage swi2 had a 25 min latent period with a large burst size (1,000 PFU/cell). The biological characteristics indicated that swi2 had good host infectivity and effective lytic activities. The genome of phage swi2 is composed of 47,611 bp with a G + C content of 46.50%. Eighty-nine orfs were predicted, and only 18 of them have known functions. No virulence genes or drug resistance genes were found in the genome. Genome sequence comparison of phage swi2 showed that there were a total of 10 homologous phages in the database with low similarity (less than 92.51% nucleotide identity and 66% query coverage). The predicted host lysis-related genes of phage swi2 consist of one holin, two endolysins, and Rz/Rz1 equivalents. Antibacterial activity assays showed that both endolysins could naturally reduce the host Escherichia coli 51 titers by -1 log unit both in vitro and in vivo, EDTA showed no obvious synergistic action, and holin had no lytic effects on the host cell. These results provide necessary information for the development of antibiotic alternatives for the treatment of multidrug-resistant Escherichia coli infection.

Background: To date, few data have been reported on clinical outcomes following interventions in elderly populations with acute basilar artery occlusion. Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study (BASILAR), we evaluated the efficacy and safety of intervention and determined predictors of outcomes among elderly patients in China. Methods: Patients from January 2014 to May 2019 were dichotomized into elderly (75 years or older) and nonelderly patients (under 75 years). Pearson’s Chi-square test and multivariate logistic regression were performed to assess 90-day favorable functional outcome (defined as a modified Rankin scale score of 0–3), mortality and symptomatic intracranial hemorrhage between intervention and conservative cohorts in elderly patients. Results: Among the 829 patients in the BASILAR, 182 patients aged 75 years or older were analyzed. These patients were divided into intervention (127 patients) and conservative (55 patients) cohorts. Compared with the conservative cohort, the intervention cohort presented more frequently with a favorable functional outcome (28.3% versus 12.7%; p = 0.023) and with a decreased mortality (54.3% versus 76.4%; p = 0.005). There was no difference in symptomatic intracranial hemorrhage (4.7% versus 0, p = 0.235). Multivariate analysis indicated that intervention was associated with favorable functional outcome (adjusted odds ratio, 0.262; 95% confidence interval, 0.088–0.778, p = 0.016) and lower mortality (adjusted odds ratio, 0.257; 95% confidence interval, 0.109–0.606, p = 0.002). In the intervention cohort, initial National Institutes of Health Stroke Scale (NIHSS) score and occlusion site were associated with functional outcome, and initial NIHSS score and recanalization were associated with mortality. Conclusions: Although the overall outcome following intervention was worse with age, intervention was more effective and safer than conservative treatment for elderly Chinese patients with basilar artery occlusion. Predictors of desirable outcome in elderly patients undergoing intervention included lower initial NIHSS score, occlusion site and successful recanalization. Clinical Trial Registration-URL: http://www.chictr.org . Unique identifier: ChiCTR-1800014759

ObjectiveAccurate preoperative identification of cervical lymph node metastasis (CLNM) is essential for clinical management and established of different surgical protocol for patients with papillary thyroid microcarcinoma (PTMC). Herein, we aimed to develop an ultrasound (US) features and clinical characteristics-based nomogram for preoperative diagnosis of CLNM for PTMC.MethodOur study included 552 patients who were pathologically diagnosed with PTMC between January 2015 and June 2019. All patients underwent total thyroidectomy or lobectomy and divided into two groups: CLNM and non-CLNM. Univariate and multivariate analysis were performed to examine risk factors associated with CLNM. A nomogram comprising the prognostic model to predict the CLNM was established, and internal validation in the cohort was performed.ResultsCLNM and non-CLNM were observed in 216(39.1%) and 336(60.9%) cases, respectively. Seven variables of clinical and US features as potential predictors including male sex (odd ratio [OR] = 1.974, 95% confidence interval [CI], 1.243-2.774; P =0.004), age < 45 years (OR = 4.621, 95% CI, 2.160-9.347; P < 0.001), US-reported CLN status (OR = 1.894, 95% CI, 0.754-3.347; P =0.005), multifocality (OR = 1.793, 95% CI, 0.774-2.649; P =0.007), tumor size ≥ 0.6cm (OR = 1.731, 95% CI,0.793-3.852; P =0.018), ETE (OR = 3.772, 95% CI, 1.752-8.441;P< 0.001) and microcalcification (OR = 2.316, 95% CI, 1.099-4.964; P < 0.001) were taken into account. The predictive nomogram was established by involving all the factors above used for preoperative prediction of CLNM in patients with PTCM. The nomogram model showed an AUC of 0.839 and an accuracy of 77.9% in predicting CLNM. Furthermore, the calibration curve demonstrated a strong consistency between nomogram and clinical findings in prediction CLNM for PTMC.ConclusionsThe nomogram achieved promising results for predicting preoperative CLNM in PTMC by combining clinical and US risk factor. Our proposed prediction model is able to help determine an individual’s risk of CLNM in PTMC, thus facilitate reasonable therapy decision making.

To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM), polysaccharides-based hydrogel microparticles as oral insulin delivery was prepared and explored. This study was aimed to evaluate the antidiabetic effects and hypoglycemic mechanism with long-term administration(four weeks) of oral insulin hydrogel microparticles in type 2 diabetic mice on a model of diabetes using a high fat diet combined with streptozotocin. The results revealed that the long-term treatment of oral insulin polysaccharides-based hydrogel microparticles could significantly alleviate the symptoms of polyphagia, polydipsia, polyuria and weight loss in diabetic mice. Also, oral administration of insulin hydrogel microparticles could significantly reduce fasting blood glucose levels, ameliorate insulin resistance and increase insulin sensitivity in the mice with T2DM. The concentration of plasma TG, TC, LDL-C, FFA, BUN, CRE significantly decreased and the levels of HDL-C increased showed that insulin polysaccharides-based hydrogel microparticles were effective in regulating lipid metabolism and prevent diabetic nephropathy complication in diabetic mice. In addition, the supplementation of insulin hydrogel microparticles could significant improve the antioxidant capacity by increasing the level of SOD, CAT and decreasing the level of MDA, GPT, NO, TNF-α, and reverse histological deterioration of kidney and pancreas in diabetic mice. The above outcome concluded that insulin polysaccharides-based hydrogel microparticles may exhibit promising anti-diabetic activity and the potential to be a drug candidate for T2DM.

Due to the influence of soil structure, structured soils exhibit significantly different mechanical behavior compared to the reconstituted soils having the same material. In this work, a theoretical analysis focusing on the mechanical behavior of structured soils is presented. Based on the mechanical behavior of the structured soil, a newly defined variable structural index was used as a measurement of the integrity of soil structure based on the concept of intrinsic compression line of intact structured soils. Furthermore, a novel correlation for the variation in volume of structured soils is established using effective stress and newly defined structural index as the constitutive variables. The novel correlation provided interpretation about the mechanism of compression behavior of the structured soils. Afterwards, the proposed correlation for the variation in volume was extended to triaxial stress state in the framework of subloading surface to include the effect of overconsolidation. Comparisons between the predictions and experimental results validated the proposed constitutive model for structured soils.

Background and aims: Recently, several clinical trials have shown that increased glycated hemoglobin (HbA1c) level is correlated with poor clinical outcomes in ischemic stroke patients after thrombolysis and possibly after mechanical thrombectomy. However, the effect of HbA1c on posterior circulation large vessel occlusion (PCLVO) patients treated with endovascular thrombectomy (EVT) remains unclear. This multicenter study assessed the association between the HbA1c levels and clinical outcomes in patients with PCLVO after EVT. Methods: We studied 385 PCLVO ischemic stroke patients included in the EVT for acute basilar artery occlusion study (BASILAR). Patients were divided into a high HbA1c level group (HbA1c >6.5%) and a low HbA1c level group (HbA1c ⩽6.5%). The efficacy outcome was a 90-day favorable functional outcome (modified Rankin Scale 0–3). The safety outcomes included symptomatic intracerebral hemorrhage and mortality at 90 days after EVT. Results: The frequency of a favorable outcome in patients with an HbA1c ⩽6.5% was significantly higher than that in the HbA1c >6.5% group (41.2% versus 26.2%, p = 0.001). In multivariate analysis with adjusted confounders, high HbA1c levels and favorable outcomes were significantly negatively correlated. There was also a significant association between high HbA1c levels and mortality after 3 months. The negative effects of high HbA1c levels on functional status after 3 months were exacerbated in patients aged ⩾65 years. Conclusion: Our multicenter study suggests that a higher serum HbA1c level (HbA1c >6.5%) is an independent predictor of a 90-day poor outcome and mortality in patients with PCLVO after EVT, particularly in those aged ⩾65 years. Clinical Trial Registry identifier: ChiCTR1800014759.

Background: Cervical lymph node (LN) metastasis of papillary thyroid carcinoma (PTC) is critical for treatment and prognosis. To examine the feasibility of MRI radiomics to preoperatively predict cervical LN metastasis in patients with PTC. Methods: Between January 2015 and March 2018, a total of 61 patients with pathologically confirmed PTC were analyzed retrospectively. The patients were divided into cervical LN metastasis group (n = 37) and no cervical LN metastasis (n = 24). T2WI and T2WI-fat-suppression (T2WI-FS) images were collected. A number of radiomic features were automatically extracted from the largest section of tumor. Three types of classifier (the random forests, the support vector machine classifier and the generalized linear model) based on T2WI and T2WI-FS images of cervical LN metastasis and no cervical LN metastasis were constructed and evaluated with a nested cross-validation scheme. Results: Radiomic features extracted from T2WI images were more discriminative than T2WI-FS images. The random forests model showed the best discriminate performance with the highest area under the curve (0.85, CI:0.76 -1), accuracy (0.87), sensitivity (0.83), specificity (1.00), positive predictive value (PPV = 1.00) and negative predictive value (NPV = 0.88). Conclusion: MRI radiomics analysis based on conventional T2WI and T2WI-FS can predict cervical LN metastasis in patients with PTC, and the radiomics is shown to be an assistant diagnosis tool for radiologists.

Background: China has experienced rapid economic growth and reduced poverty, but the associated changes of BMI categories of the Chinese population in recent years are unclear. Methods: We collected data from two-round cross-sectional National Health Service Surveys (NHSSs) conducted in China in 2013 and 2018. All family members with BMI available from the households sampled in NHSSs were included. We analyzed the standardized prevalence and changes of obesity and overweight by year, age, sex, and urban-rural area, and further identified risk factors for obesity and overweight. Findings: 273,688 individuals were included in 2013 and 25,6304 included in 2018. The standardized prevalence of obesity and overweight in adults were 19.3% (95%CI 19.1–19.4%) in 2013 and 25.6% (95%CI 25.3–25.8%) in 2018, versus 19.4% (95%CI 19·1–19.8%) in children and adolescents in 2013 and 15.8% (95%CI 15.5–16.1%) in 2018. The standardized prevalence of obesity and overweight was 16.9% (95%CI 16.0–17.3%) in young adults aged 19–29 in 2018, 48.2% higher than that in 2013 (11.4% [95%CI 11.0–11.6%]). Although the obesity and overweight prevalence was higher in urban areas, the growth rate in rural areas was 1.8 times higher than that in urban areas. Low education levels, low-income quintiles, marital status, alcohol consumption and former-smoking status were associated with higher obesity and overweight prevalence in adults. Interpretation: The rapidly increasing prevalence in young adults may lead to the growing chronic disease burden in the future, to the detriment of recent economic gains of rural families. Funding: National Health Commission of the People's Republic of China.

Background Results of several longitudinal cohort studies suggested an association between cerebral small‐vessel disease and depression. Therefore, we performed a meta‐analysis to explore whether cerebral small‐vessel disease imparts increased risk for incident depression. Methods and Results We searched prospective cohort studies relevant to the relationship between cerebral small‐vessel disease and incident depression published through September 6, 2019, which yielded 16 cohort studies for meta‐analysis based on the relative odds ratio (OR) calculated with fixed‐ and random‐effect models. Baseline white matter hyperintensities (WMHs) (pooled OR, 1.37; 95% CI, 1.14–1.65), enlarged perivascular spaces (pooled OR, 1.33; 95% CI, 1.03–1.71), and cerebral atrophy (pooled OR, 2.83; 95% CI, 1.54–5.23) were significant risk factors for incident depression. Presence of deep WMHs (pooled OR, 1.47; 95% CI, 1.05–2.06) was a stronger predictor of depression than were periventricular WMHs (pooled OR, 1.31; 95% CI, 0.93–1.86). What's more, the pooled OR increased from 1.20 for the second quartile to 1.96 for the fourth quartile, indicating that higher the WMH severity brings greater risk of incident depression (25th–50th: pooled OR, 1.20; 95% CI, 0.68–2.12; 50th–75th; pooled OR, 1.42; 95% CI, 0.81–2.46; 75th–100th: OR, 1.96; 95% CI, 1.06–3.64). These results were stable to subgroup analysis for age, source of participants, follow‐up time, and methods for assessing WMHs and depression. Conclusions Cerebral small‐vessel disease features such as WMHs, enlarged perivascular spaces, and cerebral atrophy, especially the severity of WMHs and deep WMHs, are risk factors for incident depression.

Objective: To investigate whether diffusion-weighted imaging (DWI) with multi b values can be used as a quantitative assessment tool to predict central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC).Method: A total of 214 PTC patients were enrolled from January 2015 to April 2018. Each patient underwent multi b value DWI (300, 500, and 800 s/mm2) preoperatively and then clinical treatment of central LN dissection at the Thyroid Surgery Department. These patients were divided as two groups based on with and without CLNM. The corresponding apparent diffusion coefficients (ADCs) were evaluated with separated b value, i.e., 300, 500, or 800 s/mm2. Clinicopathological variables and ADC values were analyzed retrospectively by using univariate and binary logistic regression. The corresponding obtained variables with statistical significance were further applied to create a nomogram in which the bootstrap resampling method was used for correction.Results: PTCs with CLNM had significantly lower ADC300, ADC500, and ADC800 values compared with PTCs without CLNM. Using receiver operating characteristic (ROC) analysis, the ADC500 value (0.817) showed a higher area under the curve (AUC) than those of the ADC300 and ADC800 values (0.610 and 0.641, respectively) in differentiating patients with CLNM and without CLNM. The corresponding cutoff value for ADC500 was also determined (1.444 × 10−3 mm2/s), with respective sensitivity and specificity of 88.6 and 66%. The nomogram was generated by binary logistic regression results, incorporating four variables: gender, primary tumor size, extrathyroidal extension (ETE), and ADC500 value. The AUC of the nomogram was 0.894 in predicting CLNM. Moreover, as shown in the calibration curve between nomogram and clinical findings, a strong agreement was observed in the prediction of CLNM.Conclusions: In summary, the ADC value is a valuable noninvasive imaging biomarker for evaluating CLNM in PTCs. The nomogram, as a clinical predictive model, is able to provide an effective evaluation of CLNM risk in PTC patients preoperatively.

Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.

It is usually difficult to design a controller for a nonlinear multiple-input and multiple-output (MIMO) system. The methodological approach taken in this study is a mixed methodology based on a PID-type internal model control (IMC) method and neural network (NN) optimization algorithm. The NN controller is designed for adjusting the sole parameter in IMCPID and compensating the characteristic changes and non-linearity in stepless flow control. In this study, a simulation of a nonlinear MIMO system with strong coupling is carried out. The simulation results indicate that the proposed control method has a better performance in settle time, overshoot, robustness and set-point tracking accuracy compared with other considered methods.

Copper (Cu) is essential for many physiological processes in phytoplankton, including electron-transfer reactions and high-affinity Fe transport systems. However, at high concentrations, Cu can have a toxic effect on phytoplankton. Phytoplankton’s tolerance to certain toxicants in marine ecosystems cannot always be solely attributed to the presence of compounds, as various environmental factors including temperature can also indirectly influence their effects on organisms. In this study, we investigated the effects of different Cu concentrations (0, 19.6, 160, 800, and 8000 nM) on the growth and physiological changes in the centric diatom Thalassiosira pseudonana (CCMP 1335) when simultaneously applied with temperature cultivation of 20 °C and 25 °C. At low (0 nM) and high (8000 nM) Cu concentrations, the growth rate of T. pseudonana was inhibited, though an increase in temperature lessened this inhibition. There were no significant changes in the POC:PON ratio during all of the treatments. However, increasing the temperature significantly decreased the POC: POP, PON: POP and BSi: POP ratios of T. pseudonana. The intracellular Cu content of T. pseudonana varied from 0.13 to 13.28 fg cell−1 in response to increases in ambient Cu concentrations. Lastly, an increase in the Cu concentration decreased the transcriptional expression of CTR (copper transporter), 3Hfcp (photosynthetic protein), and Sit1 (silica shell formation) encoding genes. In conclusion, our results indicated that T. pseudonana can adapt to physiological processes and molecular mechanisms in response to varying Cu concentrations and ambient temperatures.

The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump. PAR-1 expression was increased in glomeruli of mice treated with doxorubicin. Q94 treatment significantly suppressed the increased albuminuria in these nephropathic mice. Pathological analysis showed that Q94 treatment significantly attenuated periodic acidâSchiff and desmin staining, indicators of podocyte injury, and also decreased glomerular levels of podocin and nephrin. Furthermore, thrombin increased intracellular calcium levels in podocytes. This increase was suppressed by Q94 and Rox4560, a transient receptor potential cation channel (TRPC)3/6 antagonist. In addition, both Q94 and Rox4560 suppressed the doxorubicin-induced increase in activities of caspase-9 and caspase-3 in podocytes. These data suggested that PAR-1 contributes to development of podocyte and glomerular injury and that PAR-1 antagonists have therapeutic potential. Keywords: Protease-activated receptor-1, Podocyte, Transient receptor potential cation channel, Kidney injury

Abstract Nitrogen (N) is essential for the growth of algae, and its concentration varies greatly in the ocean, which has been regarded as a limitation for phytoplankton growth. Despite its great importance, most of the existing studies on the mechanisms underlying the effects of N on diatoms have focused on physiology, biochemistry and a few target genes and have rarely involved whole genomic analyses. Therefore, in this study, we integrated physiological data with RNA and protein profiling data to reveal the response strategy of Thalassiosira pseudonana under N-depleted conditions. Physiological measurements indicated that the cell growth capacity and chlorophyll content of the cells decreased, as did the expression of photosynthesis- and chlorophyll biosynthesis-related genes or proteins. The RNA-Seq profile results showed that T. pseudonana responded to N deprivation through increases in glycolysis, the TCA cycle and N metabolism as well as down-regulation in the Calvin cycle, gluconeogenesis, pentose phosphate, oxidative phosphorylation and lipid synthesis. These results provide a basic understanding for further research addressing how N affects phytoplankton in terms of genomics.

Background: The aim of this study was to evaluate associations between body-weight fluctuation and risk of mortality and cardiovascular diseases (CVD).Methods: PubMed, EMBASE databases and Cochrane Library were searched for cohort studies published up to May 20, 2019, reporting on associations of body-weight fluctuation and mortality from all causes, CVD and cancer, as well as morbidity of CVD and hypertension. Summary relative risks (RRs) were estimated using a random-effects model.Results: Twenty-five eligible publications from 23 studies with 441,199 participants were included. Body-weight fluctuation was associated with increased risk for all-cause mortality (RR, 1.41; 95% confidence interval (CI): 1.27–1.57), CVD mortality (RR, 1.36; 95% CI 1.22–1.52), and morbidity of CVD (RR, 1.49, 95% CI 1.26–1.76) and hypertension (RR, 1.35, 95% CI 1.14–1.61). However, there was no significant association between weight fluctuation and cancer mortality (RR, 1.01; 95% CI 0.90–1.13). No evidence of publication bias was observed (all P > 0.05) except for studies on all-cause mortality (Egger's test, P = 0.001; Begg's test, P = 0.014).Conclusions: Body-weight fluctuation was associated with higher mortality due to all causes and CVD and a higher morbidity of CVD and hypertension.

In recent years, miRNA variation and dysregulation have been found to be closely related to human tumors, and identifying miRNA-disease associations is helpful for understanding the mechanisms of disease or tumor development and is greatly significant for the prognosis, diagnosis, and treatment of human diseases. This article proposes a Bipartite Heterogeneous network link prediction method based on co-neighbor to predict miRNA-disease association (BHCN). According to the structural characteristics of the bipartite network, the concept of bipartite network co-neighbors is proposed, and the co-neighbors were used to represent the probability of association between disease and miRNA. To predict the isolated diseases and the new miRNA based on the association probability expressed by co-neighbors, we utilized the similarity between disease nodes and the similarity between miRNA nodes in heterogeneous networks to represent the association probability between disease and miRNA. The model's predictive performance was evaluated by the leave-one-out cross validation (LOOCV) on different datasets. The AUC value of BHCN on the gold benchmark dataset was 0.7973, and the AUC obtained on the prediction dataset was 0.9349, which was better than that of the classic global algorithm. In this case study, we conducted predictive studies on breast neoplasms and colon neoplasms. Most of the top 50 predicted results were confirmed by three databases, namely, HMDD, miR2disease, and dbDEMC, with accuracy rates of 96 and 82%. In addition, BHCN can be used for predicting isolated diseases (without any known associated diseases) and new miRNAs (without any known associated miRNAs). In the isolated disease case study, the top 50 of breast neoplasm and colon neoplasm potentials associated with miRNAs predicted an accuracy of 100 and 96%, respectively, thereby demonstrating the favorable predictive power of BHCN for potentially relevant miRNAs.

Mud crab, Scylla paramamosain is one of the most important crustacean species in global aquaculture. To determine the genetic basis of sex and growth-related traits in S. paramamosain, a high-density genetic linkage map with 16,701 single nucleotide polymorphisms (SNPs) was constructed using SLAF-seq and a full-sib family. The consensus map has 49 linkage groups, spanning 5,996.66 cM with an average marker-interval of 0.81 cM. A total of 516 SNP markers, including 8 female-specific SNPs segregated in two quantitative trait loci (QTLs) for phenotypic sex were located on LG32. The presence of female-specific SNP markers only on female linkage map, their segregation patterns and lower female: male recombination rate strongly suggest the conformation of a ZW/ZZ sex determination system in S. paramamosain. The QTLs of most (90%) growth-related traits were found within a small interval (25.18–33.74 cM) on LG46, highlighting the potential involvement of LG46 in growth. Four markers on LG46 were significantly associated with 10–16 growth-related traits. BW was only associated with marker 3846. Based on the annotation of transcriptome data, 11 and 2 candidate genes were identified within the QTL regions of sex and growth-related traits, respectively. The newly constructed high-density genetic linkage map with sex-specific SNPs, and the identified QTLs of sex- and growth-related traits serve as a valuable genetic resource and solid foundation for marker-assisted selection and genetic improvement of crustaceans.

PACRG (Parkin co-regulated gene) shares a bi-directional promoter with the Parkinson’s disease-associated gene Parkin, but the physiological roles of PACRG have not yet been fully elucidated. Recombinant expression methods are indispensable for protein structural and functional studies. In this study, the coding region of PACRG was cloned to a conventional vector pQE80L, as well as two cold-shock vectors pCold II and pCold-GST, respectively. The constructs were transformed into Escherichia coli (DE3), and the target proteins were overexpressed. The results showed that the cold-shock vectors are more suitable for PACRG expression. The soluble recombinant proteins were purified with Ni2+ chelating column, glutathione S-transferase (GST) affinity chromatography and gel filtration. His6 pull down assay and LC-MS/MS were carried out for identification of PACRG-binding proteins in HEK293T cell lysates, and a total number of 74 proteins were identified as potential interaction partners of PACRG. GO (Gene ontology) enrichment analysis (FunRich) of the 74 proteins revealed multiple molecular functions and biological processes. The highest proportion of the 74 proteins functioned as transcription regulator and transcription factor activity, suggesting that PACRG may play important roles in regulation of gene transcription.

Bafilomycin A1 is the representative compound of the plecomacrolide natural product family. This 16-membered ring plecomacrolide has potent antifungal and vacuolar H+-ATPase inhibitory activities. In our previous work, we identified a bafilomycin biosynthetic gene cluster (baf) from the marine bacterium Streptomyces lohii ATCC BAA-1276, wherein a luxR family regulatory gene orf1 and an afsR family regulatory gene bafG were revealed based on bioinformatics analysis. In this study, the positive regulatory roles of orf1 and bafG for bafilomycin biosynthesis are characterized through gene inactivation and overexpression. Compared to the wild-type S. lohii strain, the knockout of either orf1 or bafG completely abolished the production of bafilomycins. The overexpression of orf1 or bafG led to 1.3- and 0.5-fold increased production of bafilomycins, respectively. A genetically engineered S. lohii strain (SLO-08) with orf1 overexpression and inactivation of the biosynthetic genes orf2 and orf3, solely produced bafilomycin A1 with the titer of 535.1 ± 25.0 mg/L in an optimized fermentation medium in shaking flasks. This recombinant strain holds considerable application potential in large-scale production of bafilomycin A1 for new drug development.

The human dopamine D4 receptor (hD4R) variants with long tandem repeats in the third intracellular loop have been strongly associated with attention deficit hyperactivity disorder (ADHD) and risk taking behaviors. To understand the potential molecular mechanism underlying the connection, we have investigated the synaptic function of human D4R polymorphism by virally expressing the ADHD-linked 7-repeat allele, hD4.7, or its normal counterpart, hD4.4, in the prefrontal cortex (PFC) of D4R knockout mice. We found that hD4R bound to the SH3 domain of PSD-95 in a state-dependent manner. Activation of hD4.7 caused more reduction of NR1/PSD-95 binding and NR1 surface expression than hD4.4 in PFC slices. Moreover, the NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSC) in PFC pyramidal neurons were suppressed to a larger extent by hD4.7 than hD4.4 activation. Direct stimulation of NMDARs with the partial agonist d-cycloserine prevented the NMDAR hypofunction induced by hD4.7 activation. Moreover, hD4.7-expressing mice exhibited the increased exploratory and novelty seeking behaviors, mimicking the phenotypic hallmark of human ADHD. d-cycloserine administration ameliorated the ADHD-like behaviors in hD4.7-expressing mice. Our results suggest that over-suppression of NMDAR function may underlie the role of hD4.7 in ADHD, and enhancing NMDAR signaling may be a viable therapeutic strategy to ADHD humans carrying the D4.7 allele.

Abstract Background The low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness. Methods We selected those diagnosed with hypertension from patients with first-ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness. Results Of the 5309 patients with first-ever stroke, 3732 (70.3 %) were diagnosed with hypertension. Among which, 593 (15.9 %) were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy) and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends). Conclusions A substantial proportion (15.9 %) of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals.

Estuaries and coastal environments are often regarded as a critical resource for the bioremediation of organic pollutants such as azo dyes due to their high abundance and diversity of extremophiles. Bioremediation through the activities of azoreductase, laccase, and other associated enzymes plays a critical role in the removal of azo dyes in built and natural environments. However, little is known about the biodegradation genes and azo dye degradation genes residing in sediments from coastal and estuarine environments. In this study, high-throughput sequencing (16S rRNA) of sediment DNA was used to explore the distribution of azo-dye degrading bacteria and their functional genes in estuaries and coastal environments. Unlike laccase genes, azoreductase (azoR), and naphthalene degrading genes were ubiquitous in the coastal and estuarine environments. The relative abundances of most functional genes were higher in the summer compared to winter at locations proximal to the mouths of the Hanjiang River and its distributaries. These results suggested inland river discharges influenced the occurrence and abundance of azo dye degrading genes in the nearshore environments. Furthermore, the azoR genes had a significant negative relationship with total organic carbon, Hg, and Cr (p < 0.05). This study provides critical insights into the biodegradation potential of indigenous microbial communities in nearshore environments and the influence of environmental factors on microbial structure, composition, and function which is essential for the development of technologies for bioremediation in azo dye contaminated sites.

The use of social media platforms (e.g. Twitter and Facebook) to raise public awareness towards wildlife conservation is an emerging discussion. However, little is currently known about the propagation pattern of wildlife-related information on social media. In this study, a quantitative model was developed based on 230 independent cetacean stranding incidents (2008–2018) across mainland China from a popular Chinese social media platform (Sina Weibo). This model enabled analysis of the post formation process, identification of the key factors influencing the popularity of the posts and wildlife-related incidents, and allowed investigation of public opinions. The results showed that central media users can increase the overall possibility of elevating incident popularity by ∼75 times, an attractive species or incident by ∼5 times, and a negative social ethics incident by ∼3 times. Traditional media users and celebrity influencers performed key roles in affecting the level of re-posting. Online audiences of highly popular posts predominantly encompassed both users from relatively developed regions and female users. It was observed that posts which became popular within ∼12 h retained their influence for ∼3 d. Post popularity was closely related to comment counts rather than forwarding in the first day of posting and the whole status retention time. Public opinion generally expressed a supportive attitude towards wildlife conservation, but lacked in-depth thinking, and individual responsibility was expressed through revival incidents. In order to raise public awareness towards biodiversity conservation, social media–based wildlife information dissemination should balance the content of attractive and non-charismatic species or incidents and include more positive emotions. Posts via traditional users (especially central media users) and opinion leaders (celebrities) can attract a highly educated audience and females, and thus evoke increased comment numbers during the first day of posting. This will help to popularise conservation knowledge and legislation with continuous efforts.

The regulating performance degradation of the stepless capacity regulation system for reciprocating compressors occurs frequently in long-term operations. It affects the safe and stable operation of the compressor seriously. The degradation mechanisms in a stepless capacity regulation system are mainly caused by valve leakage, degeneration of the reset spring of the unloader, and (or) deviation of the solenoid valve’s characteristic parameters. In this study, to research the system performance degradation mechanisms and the influence of control parameters on system behavior, a multi-subsystem mathematics model which integrates compressor, gas pipeline, buffer tank, and actuator was built. In order to calculate the rate of degradation, a load prediction model based on a modified back-propagation neural network was established. The rate of degradation can be calculated using the predicted results. In order to optimize system regulation performance, a degradation-based optimization framework was developed which determines optimum control parameter compensation to achieve a minimum degradation rate. In addition, in order to avoid over-compensation, an adaptive control parameter compensation optimization method was adopted. According to the deviation between the given load and the prediction load, the control parameter compensations are obtained adaptively. Finally, two optimization experiments are carried out to show the effectiveness of the developed framework. The optimization results illustrate the degradation rate of the system gradually returning to normal during 60s without any over-compensation.

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac111 gene is highly conserved in lepidopteran-specific baculoviruses, and its function in the AcMNPV life cycle is still unknown. To investigate the function of ac111, an ac111-knockout AcMNPV (vAc111KO) was constructed through homologous recombination in Escherichia coli. Viral growth curve analysis and plaque assays showed that the deletion of ac111 had no effect on infectious budded virion production. Quantitative real-time polymerase chain reaction analysis confirmed that viral DNA replication was unaffected in the absence of ac111. Electron microscopy revealed that the ac111 deletion did not affect nucleocapsid assembly, occlusion-derived virion formation, or the embedding of occlusion-derived virions into the occlusion bodies. However, in vivo bioassays showed that although the deletion of ac111 did not affect the per os infectivity of AcMNPV in Spodoptera exigua larvae, it led to an approximately five-fold reduction in infectivity of AcMNPV in Trichoplusia ni larvae, and vAc111KO took approximately 21 h longer to kill Trichoplusia ni larvae than the wild-type viruses. Taken together, our results demonstrated that although ac111 is not essential for virus replication in vitro, it plays an important role in the per os infectivity of AcMNPV in a host-dependent manner.