[Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency].

OBJECTIVE: To analyze the laboratory phenotype and genetic variants of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein (PK) and High molecular weight kininogen (HMWK) deficiency and explore their molecular pathogenesis. METHODS: A PK deficiency pedigree (10 individuals from 4 generations) and a HMWK deficiency pedigree (6 individuals from 3 generations) which were admitted to the First Affiliated Hospital of Wenzhou Medical University on December 3, 2021 and June 16, 2022, respectively were selected as the study subjects. Clinical data of the two pedigrees were collected, and the related coagulation indexes of the probands and their family members were determined. Genomic DNA of the two pedigrees was extracted from peripheral blood samples. All of the exons and flanking sequences of the KLKB1 and KNG1 genes of the probands were analyzed by direct sequencing. And the corresponding sites were sequenced among other family members. Bioinformatic software was used to analyze the conservation of variation sites and the effect of variant on the protein function. RESULTS: The plasma PK activity of proband 1, a 29-year-old female, and her brother were extremely low (< 1.0%). Proband 2 was a 66-year-old male with extremely low plasma HMWK activity (< 1.0%). Genetic sequencing revealed that the proband 1 and her brother had both harbored a homozygous c.417_418insCATTCTTA (p.Arg140Hisfs*3) insertional variant in exon 5 of the KLKB1 gene. Proband 2 had harbored a homozygous c.460C>A (p.Pro154Thr) missense variant in exon 4 of the KNG1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively rated as pathogenic (PVS1+PM2_Supporting+PM4) and likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: The c.417_418insCATTCTTA (p.Arg140Hisfs*3) variant of the KLKB1 gene and the c.460C>A (p.Pro154Thr) variant of the KNG1 gene probably underlay the decreased PK and HMWK activities in the two pedigrees, respectively.

Nomogram for predicting the risk of anxiety and depression in patients with non-mild burns.

BACKGROUND: Post-burn anxiety and depression affect considerably the quality of life and recovery of patients; however, limited research has demonstrated risk factors associated with the development of these conditions. AIM: To predict the risk of developing post-burn anxiety and depression in patients with non-mild burns using a nomogram model. METHODS: We enrolled 675 patients with burns who were admitted to The Second Affiliated Hospital, Hengyang Medical School, University of South China between January 2019 and January 2023 and met the inclusion criteria. These patients were randomly divided into development (n = 450) and validation (n = 225) sets in a 2:1 ratio. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with post-burn anxiety and depression diagnoses, and a nomogram model was constructed. RESULTS: Female sex, age < 33 years, unmarried status, burn area ≥ 30%, and burns on the head, face, and neck were independent risk factors for developing post-burn anxiety and depression in patients with non-mild burns. The nomogram model demonstrated predictive accuracies of 0.937 and 0.984 for anxiety and 0.884 and 0.923 for depression in the development and validation sets, respectively, and good predictive performance. Calibration and decision curve analyses confirmed the clinical utility of the nomogram. CONCLUSION: The nomogram model predicted the risk of post-burn anxiety and depression in patients with non-mild burns, facilitating the early identification of high-risk patients for intervention and treatment.

An Evaluation of the Health Economics of Postnatal Depression Prevention and Treatment Strategies in China: A Cost-Effectiveness Analysis.

OBJECTIVE: The primary objectives of this study are to assess the cost-effectiveness of early postnatal screening and prenatal psychological interventions for the prevention and treatment of postpartum depression (PPD) among Chinese pregnant women. Additionally, we aim to explore the most cost-effective prevention and treatment strategies for PPD in China. METHODS: We used TreeAge 2019 to construct a decision tree model, with the model assuming a simulated queue size of 10,000 people. The model employed Monte Carlo simulation to assess the cost-effectiveness of PPD prevention and treatment strategies. Transfer probabilities were derived from published studies and meta-analyses. Cost and effectiveness data were obtained from published sources and relevant studies. Incremental cost-effectiveness ratios (ICERs) were used to describe the results, with willingness-to-pay (WTP) thresholds set at China's gross domestic product (GDP) per capita. RESULTS: Compared to the usual care group, the cost per additional quality-adjusted life year (QALY) for the early postnatal screening group and the prenatal psychological interventions is USD 6840.28 and USD 3720.74, respectively. The cure rate of mixed treatments for PPD has the greatest impact on the model, while patient participation in treatment has a minor impact on the cost-effectiveness of prevention and treatment strategies. CONCLUSION: Both early postnatal screening and prenatal psychological interventions are found to be highly cost-effective strategies for preventing and treating PPD in China. Prenatal psychological interventions for pregnant women are the most cost-effective prevention and treatment strategy. As such, from the perspective of national payers, we recommend that maternal screening for PPD be implemented in China to identify high-risk groups early on and to facilitate effective intervention.

Federated 3D multi-organ segmentation with partially labeled and unlabeled data.

PURPOSE: This paper considers a new problem setting for multi-organ segmentation based on the following observations. In reality, (1) collecting a large-scale dataset from various institutes is usually impeded due to privacy issues; (2) many images are not labeled since the slice-by-slice annotation is costly; and (3) datasets may exhibit inconsistent, partial annotations across different institutes. Learning a federated model from these distributed, partially labeled, and unlabeled samples is an unexplored problem. METHODS: To simulate this multi-organ segmentation problem, several distributed clients and a central server are maintained. The central server coordinates with clients to learn a global model using distributed private datasets, which comprise a small part of partially labeled images and a large part of unlabeled images. To address this problem, a practical framework that unifies partially supervised learning (PSL), semi-supervised learning (SSL), and federated learning (FL) paradigms with PSL, SSL, and FL modules is proposed. The PSL module manages to learn from partially labeled samples. The SSL module extracts valuable information from unlabeled data. Besides, the FL module aggregates local information from distributed clients to generate a global statistical model. With the collaboration of three modules, the presented scheme could take advantage of these distributed imperfect datasets to train a generalizable model. RESULTS: The proposed method was extensively evaluated with multiple abdominal CT datasets, achieving an average result of 84.83% in Dice and 41.62 mm in 95HD for multi-organ (liver, spleen, and stomach) segmentation. Moreover, its efficacy in transfer learning further demonstrated its good generalization ability for downstream segmentation tasks. CONCLUSION: This study considers a novel problem of multi-organ segmentation, which aims to develop a generalizable model using distributed, partially labeled, and unlabeled CT images. A practical framework is presented, which, through extensive validation, has proved to be an effective solution, demonstrating strong potential in addressing this challenging problem.

Revisiting instrument segmentation: Learning from decentralized surgical sequences with various imperfect annotations.

This paper focuses on a new and challenging problem related to instrument segmentation. This paper aims to learn a generalizable model from distributed datasets with various imperfect annotations. Collecting a large-scale dataset for centralized learning is usually impeded due to data silos and privacy issues. Besides, local clients, such as hospitals or medical institutes, may hold datasets with diverse and imperfect annotations. These datasets can include scarce annotations (many samples are unlabelled), noisy labels prone to errors, and scribble annotations with less precision. Federated learning (FL) has emerged as an attractive paradigm for developing global models with these locally distributed datasets. However, its potential in instrument segmentation has yet to be fully investigated. Moreover, the problem of learning from various imperfect annotations in an FL setup is rarely studied, even though it presents a more practical and beneficial scenario. This work rethinks instrument segmentation in such a setting and propose a practical FL framework for this issue. Notably, this approach surpassed centralized learning under various imperfect annotation settings. This method established a foundational benchmark, and future work can build upon it by considering each client owning various annotations and aligning closer with real-world complexities.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Profiles of digital health literacy among university students and its association with mental health during the COVID-19 pandemic: A latent profile analysis.

Objective: Investigating the digital health literacy of university students can facilitate their effective acquisition of health information and adoption of appropriate protective behaviors. This study aims to explore the subtypes of digital health literacy among university students during the COVID-19 pandemic and their association with mental health outcomes. Methods: From 17 November to 14 December 2022, a stratified random sampling approach was used to conduct an online questionnaire survey on digital health literacy, fear of COVID-19, and depression status among students at Jilin University, China. A total of 1060 valid responses were obtained in the survey. Latent profile analysis identified subtypes of digital health literacy and linear regression analyses were used to examine the association of digital health literacy to the mental health outcome. Results: Three latent profiles were identified: Profile 1-low digital health literacy (n = 66, 6.23%), Profile 2-moderate digital health literacy (n = 706, 66.60%), and Profile 3-high digital health literacy (n = 288, 27.17%). Results from linear regression demonstrated a negative correlation between digital health literacy and fear of COVID-19 (B = -2.954, P < 0.001) as well as depression (B = -2.619, P < 0.001) among university students. Conclusions: This study indicated that the majority of university students exhibit a moderate level of digital health literacy during the COVID-19 pandemic. Additionally, the study validates a negative correlation between digital health literacy and mental health among university students.

Effect of BMI on cumulative live birth rates in patients that completed IVF treatment: a retrospective cohort study of 16,126 patients.

Although several studies have reported that high maternal BMI could influence the cumulative live birth rate (CLBR) in fresh embryo transfer cycles, the association of BMI with CLBR remains unclear in patients that completed IVF treatment. In this study, we examined the association of maternal BMI with CLBR, including repetitive one oocyte pick-up (OPU) and all fresh and frozen embryo transfer until live birth or embryos were run out. A total of 16,126 patients' data were included in the analysis and were divided into four groups based on BMI. We found that patients' characteristics, embryo parameters, and pregnancy outcomes differed among different BMI groups. Multivariate logistic regression showed that being underweight was associated with a higher possibility of having live birth than the reference group (OR (95% CI) 1.40 (1.22-1.59), P < 0.001), whereas being overweight and obese were associated with a lower possibility of having live birth than the reference group ((OR (95% CI) 0.81 (0.74-0.90), P < 0.001) and (OR (95% CI) 0.68 (0.55-0.85), P < 0.001)). After adjustment for confounding factors, the reference group was associated with a higher possibility of having live birth, with a significant difference found between the obese and reference groups (OR (95% CI) 0.55 (0.43-0.70), P < 0.001). An association was found between CLBR and BMI, indicating that an increase in BMI results in a decline in CLBR. Moreover, the CLBR of patients with different characteristics differed in the various BMI groups. Taken together, our data show that maternal BMI has a significant impact on CLBR.

Moxibustion and reduced graphene oxide/cerium dioxide nanocomposites for repairing infectious wounds / 中国组织工程研究

BACKGROUND:The repair process of skin trauma is complex and susceptible to infection,easy to lead to poor healing,is the current difficulty and hot spot in wound repair research,and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering. OBJECTIVE:To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds. METHODS:(1)Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1,1:1 and 1:2 were synthesized by hydrothermal method.The resulting composites were recorded as G2C1,G1C1 and G1C2,respectively.The photothermal properties,cytotoxicity and antibacterial properties of the three kinds of materials were tested.After taking moxa sticks,three kinds of moxibustion distances were set(3.0-3.5 cm,recorded as moxibustion 1;2.5-3.0 cm,recorded as moxibustion 2;2.0-2.5 cm,recorded as moxibustion 3).Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties.The antibacterial properties of moxibustion were tested at three different distance intervals.Simultaneously,the back body surface infrared imaging of rats with different mass concentrations of G1C1 material,moxibustion(three kinds of moxibustion distances)and moxibustion 2+G1C1 material was detected.(2)Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection.48 hours later,they were randomly divided into 10 groups with 6 rats in each group:control group(did not receive any treatment),mupirocin group,moxibustion 2+G1C1 group,moxibustion 1 group,moxibustion 2 group,moxibustion 3 group and 60,80,100,and 120 μg/mL G1C1 groups(The G1C1 group was given 808 nm near-infrared laser irradiation for 10 min/time,and the G1C1 suspension was loaded on the wound surface before each treatment.Each group of moxibustion underwent in-situ suspension moxibustion,and the intervention time was 10 min/time.Moxibustion 2+G1C1 group was loaded with G1C1 suspension on the wound surface before each treatment,and moxibustion was suspended in situ with moxa strips,and the intervention time was 10 min/time).The frequency of treatment was 2 days once.Wound healing,wound colony count and repair were detected after 7 days of intervention. RESULTS AND CONCLUSION:(1)The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties,and the higher the mass concentration of the composites,the better the photothermal properties.The temperature of the moxibustion 2 group reached 47.6 ℃for 10 minutes without causing thermal damage,which was more suitable for animal experiments.The results of co-culture with NIH-3T3 cells exhibited that 60,80,and 100 μg/mL G1C1 had good biocompatibility.The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1,G1C1 and G1C2 had good antibacterial activity,among which G1C1 group demonstrated excellent antibacterial performance,and the antibacterial rate reached 100％when its mass concentration was 80 μg/mL.60-120 μg/mL G1C1 could effectively remove Staphylococcus aureus biofilm,and the higher the material mass concentration,the better the removal effect.Moxibustion could also effectively remove Staphylococcus aureus biofilm,and the closer the moxibustion was,the better the removal effect.(2)Compared with the control group,the wound area of the mupirocin group,moxibustion 2 group,moxibustion 2+G1C1 group and 80,100 μg/mL G1C1 groups was significantly reduced on day 7 of treatment,and the quality of wound repair was better.Mupirocin,G1C1,moxibustion and moxibustion 2+G1C1 could effectively remove the residual bacteria on the wound surface,and the higher the mass concentration of G1C1,the lower the residual bacteria.Among them,the wound repair efficiency and bacterial residue of 80 μg/mL G1C1 group and moxibustion 2 group were very similar,and the wound repair efficiency of both was better than that of mupirocin group.In addition,it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone.(3)The results confirm that moxibustion,reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects.

Progress of transcatheter aortic valve replacement in 2023 / 中国介入心脏病学杂志

Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.

Analysis of factors affecting diagnosis and morbidity of upper gastrointestinal cancer / 中国内镜杂志

Objective To analyze the factors affecting diagnosis and morbidity of upper gastrointestinal cancer.Methods Clinical data of 17 830 patients who were performed with upper gastrointestinal endoscopy between January 2020 and January 2022 was collected.Combined with questionnaire and pathological examination,the diagnosis and morbidity of upper gastrointestinal cancer was analyzed.Results There were 88,33 and 119 cases of carcinoma of esophagus,cardia and stomach respectively.Among them,57,27 and 91 cases of early carcinoma of esophagus,cardia and stomach were found.They were divided into the observation group(240 cases)and control group(17 590 cases).Univariate analysis showed significant differences between the two groups in education,drinking,pickled food,atrophic gastritis,intraepithelial neoplasia,painless gastroscopy,standard gastroscopy,and anxiety.Multivariate unconditional Logistic regression analysis and propensity score matching showed that drinking,atrophic gastritis,pickled food,intraepithelial neoplasia and anxiety were risk factors influencing the diagnosis and morbidity of upper gastrointestinal cancer.Conclusion Drinking,atrophic gastritis,pickled food,intraepithelial neoplasia and anxiety are risk factors influencing the diagnosis and morbidity of upper gastrointestinal cancer.Adjust the diet and life style,enhance the awareness of early cancer screening,can control the risk factors influencing the diagnosis and morbidity of upper gastrointestinal cancer.

The First Application of Domestically Produced Self-expanding Transcatheter Aortic Valve Controllable Bending Delivery System in China / 中国循环杂志

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.

Augmented surveillance of antimicrobial resistance with high-throughput robotics detects transnational flow of fluoroquinolone-resistant Escherichia coli strain into poultry.

BACKGROUND: Food animal AMR surveillance programs assess only small numbers of Escherichia coli (from 100 to 600 per animal class) nationally each year, severely limiting the evaluation of public health risk(s). Here we demonstrate an affordable approach for early detection of emerging resistance on a broad scale that can also accurately characterize spatial and temporal changes in resistance. METHODS: Caecal samples (n = 295) obtained from 10 meat poultry were screened using high-throughput robotics. Initial screening via agar dilution (5310 plates) quantified AMR carriage (cfu/g) for each sample. Ciprofloxacin-resistant isolates (n = 91) proceeded to downstream broth microdilution susceptibility testing. A subset of 28 ciprofloxacin-resistant isolates underwent WGS and phylogenetic analysis. RESULTS: Intra- and inter-flock carriage of resistance varied with drug class. Ampicillin and tetracycline resistance was ubiquitous to most birds in all flocks with an average carriage rate of 5.8 log10 cfu/g. Gentamicin and ciprofloxacin-resistant E. coli colonized fewer birds, and had an average carriage rate of 1.2 log10 cfu/g and 1.0 log10 cfu/g of faeces, respectively. Resistance to extended-spectrum cephalosporins was absent. ST354 was the dominant ST among the WGS isolates, but they demonstrated markedly lower resistance gene carriage than their international counterparts. CONCLUSIONS: These data amply demonstrate the ineffectiveness of commonly relied-on approaches to AMR surveillance for achieving early detection of emergence, or for measuring spatial and temporal resistance trends. Genetic analysis suggested there has been transnational flow of a ciprofloxacin-resistant strain into Australian poultry flocks, explaining their detection in a nation that prohibits fluoroquinolone use in poultry.

Kruppel homolog 1 modulates ROS production and antimicrobial peptides expression in shrimp hemocytes during infection by the Vibrio parahaemolyticus strain that causes AHPND.

Shrimp aquaculture has been seriously affected by acute hepatopancreatic necrosis disease (AHPND), caused by a strain of Vibrio parahaemolyticus that carries the Pir toxin plasmids (V. parahaemolyticus (AHPND)). In this study, the transcription factor, Kruppel homolog 1-like of Peneaus vannamei (PvKr-h1), was significantly induced in shrimp hemocytes after V. parahaemolyticus (AHPND) challenge, suggesting that PvKr-h1 is involved in shrimp immune response. Knockdown of PvKr-h1 followed by V. parahaemolyticus (AHPND) challenge increased bacterial abundance in shrimp hemolymph coupled with high shrimp mortality. Moreover, transcriptome and immunofluorescence analyses revealed that PvKr-h1 silencing followed by V. parahaemolyticus (AHPND) challenge dysregulated the expression of several antioxidant-related enzyme genes, such as Cu-Zu SOD, GPX, and GST, and antimicrobial peptide genes, i.e., CRUs and PENs, and reduced ROS activity and nuclear translocation of Relish. These data reveal that PvKr-h1 regulates shrimps' immune response to V. parahaemolyticus (AHPND) infection by suppressing antioxidant-related enzymes, enhancing ROS production and promoting nuclei import of PvRelish to stimulate antimicrobial peptide genes expression.

Adropin attenuates pancreatitis­associated lung injury through PPARγ phosphorylation­related macrophage polarization.

Acute pancreatitis (AP)­associated lung injury (ALI) is a critical complication of AP. Adropin is a regulatory protein of immune metabolism. The present study aimed to explore the immunomodulatory effects of adropin on AP­ALI. For this purpose, serum samples of patients with AP were collected and the expression levels of serum adropin were detected using ELISA. Animal models of AP and adropin knockout (Adro­KO) were constructed, and adropin expression in serum and lung tissues was investigated. The levels of fibrosis and apoptosis were evaluated using hematoxylin and eosin staining, Masson's staining and immunohistochemistry of in lung tissue. M1/M2 type macrophages in the lungs were detected using immunofluorescence staining, western blot analysis and reverse transcription­quantitative PCR. As shown by the results, adropin expression was decreased in AP. In the Adro­KO + L­arginine (L­Arg) group, macrophage infiltration, fibrosis and apoptosis were increased. The expression of peroxisome proliferator­ activated receptor γ (PPARγ) was downregulated, and the macrophages exhibited a trend towards M1 polarization in the Adro­KO + L­Arg group. Adropin exogenous supplement attenuated the levels of fibrosis and apoptosis in the model of AP. Adropin exogenous supplement also increased PPARγ expression by the regulation of the phosphorylation levels, which was associated with M2 macrophage polarization. On the whole, the findings of the present study suggest that adropin promotes the M2 polarization of lung macrophages and reduces the severity of AP­ALI by regulating the function of PPARγ through the regulation of its phosphorylation level.

A national study confirms that Escherichia coli from Australian commercial layer hens remain susceptible to critically important antimicrobials.

Controlling the use of the most critically important antimicrobials (CIAs) in food animals has been identified as one of the key measures required to curb the transmission of antimicrobial resistant bacteria from animals to humans. Expanding the evidence demonstrating the effectiveness of restricting CIA usage for preventing the emergence of resistance to key drugs amongst commensal organisms in animal production would do much to strengthen international efforts to control antimicrobial resistance (AMR). As Australia has strict controls on antimicrobial use in layer hens, and internationally comparatively low levels of poultry disease due to strict national biosecurity measures, we investigated whether these circumstances have resulted in curtailing development of critical forms of AMR. The work comprised a cross-sectional national survey of 62 commercial layer farms with each assessed for AMR in Escherichia coli isolates recovered from faeces. Minimum inhibitory concentration analysis using a panel of 13 antimicrobials was performed on 296 isolates, with those exhibiting phenotypic resistance to fluoroquinolones (a CIA) or multi-class drug resistance (MCR) subjected to whole genome sequencing. Overall, 53.0% of isolates were susceptible to all antimicrobials tested, and all isolates were susceptible to cefoxitin, ceftiofur, ceftriaxone, chloramphenicol and colistin. Resistance was observed for amoxicillin-clavulanate (9.1%), ampicillin (16.2%), ciprofloxacin (2.7%), florfenicol (2.4%), gentamicin (1.0%), streptomycin (4.7%), tetracycline (37.8%) and trimethoprim/sulfamethoxazole (9.5%). MCR was observed in 21 isolates (7.0%), with two isolates exhibiting resistance to four antimicrobial classes. Whole genome sequencing revealed that ciprofloxacin-resistant (fluoroquinolone) isolates were devoid of both known chromosomal mutations in the quinolone resistance determinant regions and plasmid-mediated quinolone resistance genes (qnr)-other than in one isolate (ST155) which carried the qnrS gene. Two MCR E. coli isolates with ciprofloxacin-resistance were found to be carrying known resistance genes including aadA1, dfrA1, strA, strB, sul1, sul2, tet(A), blaTEM-1B, qnrS1 and tet(A). Overall, this study found that E. coli from layer hens in Australia have low rates of AMR, likely due to strict control on antimicrobial usage achieved by the sum of regulation and voluntary measures.

Hybrid coordination for the fast formation building of multi-small-AUV systems with the on-board cameras and limited communication.

Formation building for multi-small-AUV systems with on-board cameras is crucial under the limited communication underwater environment. A hybrid coordination strategy is proposed for the rapid convergence to a leader-follower pattern. The strategy consists of two parts: a time-optimal local-position-based controller (TOLC) and a distributed asynchronous discrete weighted consensus controller (ADWCC). The TOLC controller is designed to optimize the assignation of AUVs' destinations in the given pattern and guide each AUV to its destination by the shortest feasible distance. The ADWCC controller is developed to direct the AUVs blocked by obstacles to reach their destinations with the information from the perceived neighbors by on-board cameras. The rapidity of the proposed strategy is theoretically discussed. The effectiveness of the proposed algorithm has been verified in the simulation environments in both MATLAB and Blender.

Neuropilin 1 is an entry receptor for KSHV infection of mesenchymal stem cell through TGFBR1/2-mediated macropinocytosis.

Kaposi's sarcoma-associated herpesvirus (KSHV) has been implicated in the pathogenesis of Kaposi's sarcoma (KS) and other malignancies. The cellular origin of KS has been suggested to be either mesenchymal stem cells (MSCs) or endothelial cells. However, receptor(s) for KSHV to infect MSCs remains unknown. By combining bioinformatics analysis and shRNA screening, we identify neuropilin 1 (NRP1) as an entry receptor for KSHV infection of MSCs. Functionally, NRP1 knockout and overexpression in MSCs significantly reduce and promote, respectively, KSHV infection. Mechanistically, NRP1 facilitated the binding and internalization of KSHV by interacting with KSHV glycoprotein B (gB), which was blocked by soluble NRP1 protein. Furthermore, NRP1 interacts with TGF-ß receptor type 2 (TGFBR2) through their respective cytoplasmic domains and thus activates the TGFBR1/2 complex, which facilitates the macropinocytosis-mediated KSHV internalization via the small GTPases Cdc42 and Rac1. Together, these findings implicate that KSHV has evolved a strategy to invade MSCs by harnessing NRP1 and TGF-beta receptors to stimulate macropinocytosis.

Ancylobacter mangrovi sp. nov., a novel endophytic bacterium isolated from mangrove plant.

Two novel strains GSK1Z-4-2T and MQZ15Z-1 were isolated from branches of mangrove plants collected from Guangxi Zhuang Autonomous Region, China. Both strains were Gram-negative, aerobic, non-flagellated and non-spore-forming bacteria. The comparison of 16S rRNA gene sequences initially indicated that the two strains were assigned to the genus Ancylobacter with sharing the highest similarity to Ancylobacter pratisalsi DSM 102029T (97.3%). The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strains GSK1Z-4-2T and MQZ15Z-1 were 99.9%, 97.4% and 77.4%, respectively, which revealed that the two strains belonged to the same species. Phylogenetic analyses based on 16S rRNA gene sequences and the core proteome showed that the two strains formed a well-supported cluster with A. pratisalsi DSM 102029T. Moreover, the ANI and isDDH values between strain GSK1Z-4-2T and A. pratisalsi DSM 102029T were 83.0% and 25.8%, respectively, demonstrating that strain GSK1Z-4-2T was a previously undescribed species. Meanwhile, strains GSK1Z-4-2T and MQZ15Z-1 exhibited most of chemotaxonomic and phenotypic features consistent with the description of the genus Ancylobacter. Based on the polyphasic data, strains GSK1Z-4-2T and MQZ15Z-1 should represent a novel species of the genus Ancylobacter, for which the name Ancylobacter mangrovi sp. nov. is proposed. The type strain is GSK1Z-4-2T (=MCCC 1K07181T = JCM 34924T).