Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

A Functionally Asymmetric Janus Hygro-Photothermal Hybrid for Atmospheric Water Harvesting in Arid Regions.

Metal-organic frameworks (MOFs) are high-performance adsorbents for atmospheric water harvesting but have poor water-desorption ability, requiring excess energy input to release the trapped water. Addressing this issue, a Janus-structured adsorbent with functional asymmetry is presented. The material exhibits contrasting functionalities on either face - a hygroscopic face interfaced with a photothermal face. Hygroscopic aluminum fumarate MOF and photothermal CuxS layers are in-situ grown on opposite sides of a Cu/Al bimetallic substrate, resulting in a CuxS-Cu/Al-MOF Janus hygro-photothermal hybrid. The two faces serve as independent "factories" for photothermal conversion and water adsorption-desorption respectively, while the interfacing bimetallic layer serves as a "heat conveyor belt" between them. Due to the high porosity and hydrophilicity of the MOF, the hybrid exhibits a water-adsorption capacity of 0.161 g g-1 and a fast adsorption rate (saturation within 52 min) at 30% relative humidity. Thanks to the photothermal CuxS, the hybrid can reach 71.5 °C under 1 Sun in 20 min and desorb 97% adsorbed water in 40 min, exhibiting a high photothermal conversion efficiency of over 90%. CuxS-Cu/Al-MOF exhibits minimal fluctuations after 200 cycles, and its water-generation capacity is 3.21 times that of powdery MOF in 3 h in a self-designed prototype in one cycle.

Outer Membrane Vesicles Transmitting blaNDM-1 Mediate the Emergence of Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae.

Dissemination of hypervirulent and carbapenem-resistant Klebsiella pneumoniae (CRKP) has been reported worldwide, posing a serious threat to antimicrobial therapy and public health. Outer membrane vesicles (OMVs) act as vectors for the horizontal transfer of virulence and resistance genes. However, K. pneumoniae OMVs that transfer carbapenem resistance genes into hypervirulent K. pneumoniae (hvKP) have been insufficiently investigated. Therefore, this study investigates the transmission of the blaNDM-1 gene encoding resistance via OMVs released from CRKP and the potential mechanism responsible for the carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) emergence. OMVs were isolated via ultracentrifugation from CRKP with or without meropenem selective pressure. OMVs were then used to transform classical K. pneumoniae (ckp) ATCC 10031, extended-spectrum ß-lactamase (ESBL)-producing K. pneumoniae ATCC 700603, and hvKP NTUH-K2044. Our results showed that meropenem treatment resulted in changes in the number and diameter of OMVs secreted by CRKP. OMVs derived from CRKP mediated the transfer of blaNDM-1 to ckp and hvKP, thereby increasing the carbapenem MIC of transformants. Further experiments confirmed that NTUH-K2044 transformants exhibited hypervirulence. Our study demonstrates, for the first time, that OMVs derived from CRKP can carry blaNDM-1 and deliver resistance genes to other K. pneumoniae strains, even hvKP. The transfer of carbapenem genes into hypervirulent strains may promote the emergence and dissemination of CR-hvKP. This study elucidates a new mechanism underlying the formation of CR-hvKP.

Bimetallic MOF-Derived Solar-Triggered Monolithic Adsorbent for Enhanced Atmospheric Water Harvesting.

The development of economical, energy-saving, and efficient metal-organic framework (MOF)-based adsorbents for atmospheric water collection is highly imperative for the rapid advancement of renewable freshwater resource exploitation. Herein, a feasible one-step solvothermal formation strategy of bimetallic MOF (BMOF) is proposed and applied to construct a solar-triggered monolithic adsorbent for enhanced atmospheric water collection. Benefiting from the reorganization and adjustment of topology structure by Al atoms and Fe atoms, the resultant BMOF(3) consisting of Al-fumarate and MIL-88A has a higher specific surface area (1202.99 m2  g-1 ) and pore volume (0.51 cm3  g-1 ), thereby outperforming the parental MOFs and other potential MOFs in absorbing water. Expanding upon this finding, the solar-triggered monolithic adsorbent is further developed through a bottom-up assembly of polyaniline/chitosan layers and hybridized BMOF(3) skeletons on a glass fiber support. The resultant monolithic adsorbent exhibits superior sorption-desorption kinetics, leading to directional water transport and rapid solar-assisted vapor diffusion. As a proof-of-concept demonstration, an exquisite water harvester is constructed to emphasize a high water yield of 1.19 g g-1 per day of the designed monolithic adsorbent. Therefore, the design and validation of bimetallic MOF-derived solar-triggered adsorbent in this work are expected to provide a reference for the large-scale applications of MOF-based atmospheric water harvesting.

The genome evolution of Marek's disease viruses in chickens and turkeys in China.

The virus that causes Marek's disease (MD) is globally ubiquitous in chickens, continuously evolving, and poses a significant threat to the poultry industry. Although vaccines are extensively used, MD still occurs frequently and the virus has evolved increased virulence in China. Here, we report an outbreak of MD in vaccinated chickens and unvaccinated turkeys in a backyard farm in Guangdong province, China, in 2018. Phylogenetic analysis revealed two lineages of MDVs at this farm, with one lineage, containing isolates from two turkeys and five chickens, clustering with virulent Chinese strains and displays a relatively high genetic divergence from the vaccine strains. These new isolates appear to have broken through vaccine immunity, yielding this outbreak of MD in chickens and turkeys. The second lineage included four chicken isolates that clustered with the CVI988 and 814 vaccine strains. The large diversity of MDVs in this single outbreak reveals a complex circulation of MDVs in China. Poor breeding conditions and the weak application of disease prevention and control measures make backyard farms a hotbed for the evolution of viruses that cause infectious diseases. This is especially important in MDV as the MD vaccines do not provide sterilizing immunity, which allows the replication and shedding of virulent field viruses by vaccinated individuals and supporting the continuous evolution of MDVs. Hence, constant monitoring of the evolution of MDVs is necessary to understand the evolution of these field viruses and potential expansions of their host range.

Molecular epidemiology of clinical isolation of carbapenem-resistant Enterobacterales and application of carbapenemase inhibitor enhancement test. / ä¸´åºŠåˆ†ç¦»ç¢³é’éœ‰çƒ¯ç±»è€è¯è‚ æ†èŒç›®ç»†èŒèŒæ ªçš„åˆ†å­æµè¡Œç— å­¦åŠç¢³é’éœ‰çƒ¯é ¶æŠ‘åˆ¶å‰‚å¢žå¼ºè¯•éªŒçš„åº”ç”¨.

OBJECTIVES: The prevalence of carbapenem-resistant Enterobacterales (CRE) presents a significant challenge in clinical anti-infective treatment. This study aims to investigate drug resistance and the molecular epidemiological characteristics of CRE in our area. Additionally, we seek to evaluate practicality of utilizing carbapenemase inhibitor enhancement test in clinical laboratory. METHODS: Non-repeated CREs isolated from clinical specimens at Xiangya Hospital, Central South University, were collected. Minimum inhibitory concentration (MIC) combined with Kirby-Bauer (KB) assay was used to detect the drug susceptibility of the strains, and 13 carbapenemase-producing genes were detected by PCR. The phenotype of 126 strains of carbapenemase-producing Enterobacterales identified by PCR was detected by the carbapenemase inhibitor enhancement test to understand the agreement between the method and the gold standard PCR results. RESULTS: Among 704 CRE strains examined, we observed significant drug resistance in 501 strains dentified as carbapenemase-producing Enterobacterales (CPE). Klebsiella pneumoniae was the predominant CPE strain, followed by Enterobacter cloacae and Escherichia coli. A total of 9 carbapenemase types were detected, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-ß-lactamase (NDM), Verona integron- encoded metallo-ß-lactamases (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48), and rare imipenem-hydrolyzing ß-lactamase (IMI), adelaide imipenemase (AIM), Bicêtre carbapenemase (BIC), and guiana extended-spectrum ß-lactamase (GES). The detection rate of KPC serine carbapenemase was 61.7% (309/501). The carbapenemase inhibitor enhancement test exhibited a 100% consistency rate for the strains producing Class A serine carbapenemase and/or Class B metallo-ß-lactamases. CONCLUSIONS: CRE strains in Changsha, Hunan, China, are wide distribution and exhibit carbapenemase production. The main mechanism of carbapenem resistance in these bacterias is predominatly attributed to the production of KPC serine carbapenemase. The presence of GES and IMI genes carried by Enterobacterales has been detected for the first time in this region. The carbapenemase inhibitor enhancement test has been proven to be an accurate method for detecting CRE producing Class A serine carbapenemase and/or Class B metallo-ß-lactamases. This method offers simpicity of operation and ease of results interpretation, making it weel-suited meeting the clinical microbiology laboratory's reguirements for the detection of serine carbapenemase and metallo-ß-lactamases.

Anti-citrullinated protein antibodies are associated with neutrophil extracellular trap formation in rheumatoid arthritis.

OBJECTIVES: We evaluated the associations of anti-citrullinated protein antibodies (ACPAs) and serological and cytological levels of neutrophil extracellular trap (NET) formation in rheumatoid arthritis (RA) patients. METHODS: Serum levels of myeloperoxidase-DNA and elastase-DNA complexes (NET remnants) were examined in 51 patients with RA and 40 healthy controls using a modified enzyme-linked immunosorbent assay. Neutrophils were isolated by density gradient centrifugation. IgG antibodies were purified by affinity chromatography. NET formation in RA and control neutrophils was assessed by microscopy in vitro. NETs were purified and co-incubated with fibroblast-like synoviocyte (FLS) cells. Interleukin (IL)-6 and IL-8 mRNA expression and protein levels in FLS cells were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: In RA patients, NET remnants in the peripheral circulation were higher in extremely high ACPA titers when compared to in moderate ACPA titers. And IgG antibodies containing ACPA can stimulate neutrophils to form NETs in a concentration-dependent manner. Furthermore, significantly higher expression of the pro-inflammatory cytokines IL-6 and IL-8 is detected after FLS cells interacted with NETs which derived from neutrophils stimulated with ACPA-containing IgG antibodies. CONCLUSIONS: Anti-citrullinated protein antibodies may enhance NET formation and contribute to inflammation development in RA by stimulating NET formation, such as by subsequent activation of FLS cells by NETs.

Increased levels of serum histone H4 and activated protein C in patients with active rheumatoid arthritis.

OBJECTIVES: We aimed to examine the levels of serum H4 and activated protein C (APC) in rheumatoid arthritis (RA) and other autoimmune conditions, and investigate the associations between H4 or APC levels and disease activity indicators in RA. METHODS: Serum H4 and APC distribution was examined in samples from patients with RA, systemic lupus erythematosus (SLE), polymyositis (PM), and ankylosing spondylitis (AS), as well as in samples from healthy controls, using commercial ELISA kits. Associations of serum H4 or APC levels with disease variables in patients with RA were evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminant capacity of APC against RA and non-RA. RESULTS: The patients with RA, PM, and AS showed higher serum levels of H4 and APC than those from the healthy control individuals, while the SLE patients showed higher serum levels of APC only. Moderate positive correlations between H4 levels and absolute neutrophil count (ANC), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), brinogen (FIB), D-dimer (DD), and complement fraction 3 (C3) were observed. Positive correlations between APC levels and PLT, RF, DD, or DAS28 were additionally found. ROC curve analysis revealed that APC discriminated well between RA and non-RA. CONCLUSIONS: H4 and APC concentrations are elevated in patients with chronic in ammatory autoimmune diseases. The observed associations between H4 and APC and disease variables in patients with RA support a role for H4 and APC in the in ammatory process of the disease.

Emergence and spread of O16-ST131 and O25b-ST131 clones among faecal CTX-M-producing Escherichia coli in healthy individuals in Hunan Province, China.

OBJECTIVES: The objectives of this study were to determine CTX-M-producing Escherichia coli ST131 strain prevalence in stool specimens from healthy subjects in central China and to molecularly characterize clonal groups. METHODS: From November 2013 to January 2014, stool specimens from healthy individuals in Hunan Province were screened for ESBL-producing E. coli using chromogenic medium and CTX-M genotypes and phylogenetic groups were determined. ST131 clonal groups were detected by PCR and characterized for antibiotic resistance, fimH, gyrA and parC alleles, plasmid-mediated quinolone resistance determinants, virulence genotypes and PFGE patterns. RESULTS: Among 563 subjects, 287 (51.0%) exhibited the presence of faecal ESBL-producing E. coli, all of which produced CTX-M enzymes. The most common CTX-M genotypes were CTX-M-14 (48.4%), CTX-M-15 (27.5%) and CTX-M-27 (15.0%). Of the 287 CTX-M-producing isolates, 32 (11.1%) belonged to the ST131 clone. O16-ST131 isolates were dominant (75%) and contained the fimH41 allele. The remaining eight (25%) ST131 isolates were of the O25b subgroup and contained fimH30 or fimH41. Ciprofloxacin resistance was found in 100% of the O25b-ST131 isolates, whereas only 8% of the O16-ST131 isolates were resistant. All of the O25b-ST131 isolates except one showed gyrA1AB and parC1aAB mutations; most of the O16-ST131 isolates had gyrA1A and parC1b mutations. The virulence genotypes of O16-ST131 resembled those of the O25b-ST131 isolates. The 32 ST131 isolates formed one large group at the 64% similarity level. They comprised 15 PFGE groups (defined at ≥85% similarity). CONCLUSIONS: O16-ST131 isolates have emerged as the predominant type of ST131 isolate in faecal CTX-M-producing E. coli in healthy individuals in China.

Homogeneous and Label-Free Detection and Monitoring of Protein Kinase Activity Using the Impact Electrochemistry of Silver Nanoparticles.

Protein kinase activity correlates closely with that of many human diseases. However, the existing methods for quantifying protein kinase activity often suffer from limitations such as low sensitivity, harmful radioactive labels, high cost, and sophisticated detection procedures, underscoring the urgent need for sensitive and rapid detection methods. Herein, we present a simple and sensitive approach for the homogeneous detection of protein kinase activity based on nanoimpact electrochemistry to probe the degree of aggregation of silver nanoparticles (AgNPs) before and after phosphorylation. Phosphorylation, catalyzed by protein kinases, introduces two negative charges into the substrate peptide, leading to alterations in electrostatic interactions between the phosphorylated peptide and the negatively charged AgNPs, which, in turn, affects the aggregation status of AgNPs. Via direct electro-oxidation of AgNPs in nanoimpact electrochemistry experiments, protein kinase activity can be quantified by assessing the impact frequency. The present sensor demonstrates a broad detection range and a low detection limit for protein kinase A (PKA), along with remarkable selectivity. Additionally, it enables monitoring of PKA-catalyzed phosphorylation processes. In contrast to conventional electrochemical sensing methods, this approach avoids the requirement of complex labeling and washing procedures.

Symbiotic defect-reinforced bimetallic MOF-derived fiber components for solar-assisted atmospheric water collection.

Conversion of atmospheric water to sustainable and clean freshwater resources through MOF-based adsorbent has great potential for the renewable environmental industry. However, its daily water production is hampered by susceptibility to agglomeration, slow water evaporation efficiency, and limited water-harvesting capacity. Herein, a solar-assisted bimetallic MOF (BMOF)-derived fiber component that surmounts these limitations and exhibits both optimized water-collect capacity and short adsorption-desorption period is proposed. The proposed strategy involves utilizing bottom-up interface-induced assembly between carboxylated multi-walled carbon nanotube and hygroscopic BMOF on a multi-ply glass fiber support. The designed BMOF (MIL-100(Fe,Al)-3) skeleton constructed using bimetallic-node defect engineering exhibits a high specific surface area (1,535.28 m2/g) and pore volume (0.76 cm3/g), thereby surpassing the parent MOFs and other reported MOFs in capturing moisture. Benefiting from the hierarchical structure of fiber rods and the solar-driven self-heating interface of photothermal layer, the customized BMOF crystals realize efficient loading and optimized water adsorption-desorption kinetics. As a result, the resultant fiber components achieve six adsorption-desorption cycles per day and an impressive water collection of 1.45 g/g/day under medium-high humidity outdoor conditions. Therefore, this work will provide new ideas for optimizing the daily yield of atmospheric water harvesting techniques.

Multiclass malaria parasite recognition based on transformer models and a generative adversarial network.

Malaria is an extremely infectious disease and a main cause of death worldwide. Microscopic examination of thin slide serves as a common method for the diagnosis of malaria. Meanwhile, the transformer models have gained increasing popularity in many regions, such as computer vision and natural language processing. Transformers also offer lots of advantages in classification task, such as Fine-grained Feature Extraction, Attention Mechanism etc. In this article, we propose to assist the medical professionals by developing an effective framework based on transformer models and a generative adversarial network for multi-class plasmodium classification and malaria diagnosis. The Generative Adversarial Network is employed to generate extended training samples from multiclass cell images, with the aim of enhancing the robustness of the resulting model. We aim to optimize plasmodium classification to achieve an exact balance of high accuracy and low resource consumption. A comprehensive comparison of the transformer models to the state-of-the-art methods proves their efficiency in the classification of malaria parasite through thin blood smear microscopic images. Based on our findings, the Swin Transformer model and MobileVit outperform the baseline architectures in terms of precision, recall, F1-score, specificity, and FPR on test set (the data was divided into train: validation: test splits). It is evident that the Swin Transformer achieves superior detection performance (up to 99.8% accuracy), while MobileViT demonstrates lower memory usage and shorter inference times. High accuracy empowers healthcare professionals to conduct precise diagnoses, while low memory usage and short inference times enable the deployment of predictive models on edge devices with limited computational and memory resources.

Incidence, antimicrobial resistance and mortality of Pseudomonas aeruginosa bloodstream infections among hospitalized patients in China: a retrospective observational multicenter cohort study from 2017 to 2021.

Background: Pseudomonas aeruginosa (P. aeruginosa) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). We aim to investigate incidence, antimicrobial resistance and risk factors for mortality of P. aeruginosa BSIs among inpatients. Methods: A retrospective cohort study were conducted at two tertiary hospitals in 2017-2021. Medical and laboratory records of all inpatients diagnosed with P. aeruginosa BSIs were reviewed. A generalized linear mixed model was used to identify risk factors for mortality. Results: A total of 285 patients with P. aeruginosa BSIs were identified. Incidence of P. aeruginosa BSIs fluctuated between 2.37 and 3.51 per 100,000 patient-days over the study period. Out of 285 P. aeruginosa isolates, 97 (34.04%) were carbapenem-resistant (CR) and 75 (26.32%) were multidrug-resistant (MDR). These isolates showed low resistance to aminoglycosides (9.51-11.62%), broad-spectrum cephalosporins (17.19-17.61%), fluoroquinolones (17.25-19.43%), and polymyxin B (1.69%). The crude 30-day mortality rate was 17.89% (51/285). Healthcare costs of patients with MDR/CR isolates were significantly higher than those of patients with non-MDR/CR isolates (P < 0.001/=0.002). Inappropriate definitive therapy [adjusted odds ratio (aOR) 4.47, 95% confidence interval (95% CI) 1.35-14.77; P = 0.014], ICU stay (aOR 2.89, 95% CI: 1.26-6.63; P = 0.012) and corticosteroids use (aOR 2.89, 95% CI: 1.31-6.41; P = 0.009) were independently associated with 30-day mortality. Conclusion: Incidence of P. aeruginosa BSIs showed an upward trend during 2017-2020 but dropped in 2021. MDR/CR P. aeruginosa BSIs are associated with higher healthcare costs. Awareness is required that patients with inappropriate definitive antimicrobial therapy, ICU stay and corticosteroids use are at higher risk of death from P. aeruginosa BSIs.

A novel auxiliary diagnostic model for COVID-19 screening using enzymes based detection of serum biomarkers and clinical characteristics.

The screening for the coronavirus disease 2019 (COVID-19) based on virus nuclear acid detection and radiology has encountered unprecedented difficulties due to the shortage of kits and facilities, and the lack of sensitivity and specificity, especially for developing countries. The study aimed to develop an auxiliary diagnostic score based on age, biomarkers, clinical characteristics (ABC) to rapidly and accurately screen COVID-19. Serum biomarkers were detected by enzymes catalyzed reaction method which is rapid and accurate. A retrospective case-control study among Chinese patients with laboratory-confirmed COVID-19 and those without COVID-19 was conducted. Data of age, sex, signs and symptoms, history of disease, complete blood counts, and serum biochemical items such as ALT and AST were used to establish the diagnostic model. ALT/AST was detected by enzymes based biochemical reaction method. Stepwise logistic regression and random forests with variable selection process were used to establish the model. Ten-fold cross-validation and out-of-bag error were used to assess the accuracy of the models. Decision curve analysis was used to compare different models. A total of 279 cases and 253 controls were recruited, with mean age of 60.7 ± 13.7 and 42.6 ± 20.2, respectively. The regression model selected nine variables with Kappa of 0.77, sensitivity of 0.90, and specificity of 0.87. The random forests retained eight variables with Kappa of 0.76, sensitivity of 0.87, and specificity of 0.89. Based on decision curve analysis, the ABC-based diagnostic score provided the largest net benefit compared to other models with less data input. Subgroup analysis by excluding severely ill cases showed a decreased but acceptable sensitivity (0.75) and unchanged overall accuracy. The ABC-based diagnostic score provides a rapid and valid method for COVID-19 screening, especially for regions with a shortage of facilities. The model performs less well in the diagnosis of mild-to-moderate COVID-19.

Prognostic value of blood inflammatory parameters for predicting mortality in neonates with sepsis.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in neonates. The diagnosis of neonatal sepsis has been widely explored using blood inflammatory parameters. However, few researches have focused on the predictive significance of blood inflammation parameters for predicting mortality. This study aimed to evaluate the prognostic value of blood inflammatory parameters, including white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet and C-reactive protein (CRP) for predicting mortality in neonates with sepsis. METHODS: Neonates with culture-proven sepsis were enrolled in this study. The clinical characteristics and levels of white blood cell, neutrophil, lymphocyte, monocyte, platelet and CRP were recorded. The receiver-operating characteristic (ROC) curve was applied to calculate the area under the curve (AUC) and determine the optimal cutoff values. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. Kaplan-Meier curve was used to assess survival. RESULTS: A total of 188 neonates with culture-proven sepsis were included for analysis. The 7-day mortality rate was 11.2 % (21/188) and the 28-day mortality rate was 13.8 % (26/188). The levels of white blood cell, neutrophil, monocyte and platelet in non-survivors were lower than those in survivors (P < 0.05). Platelet yielded higher AUC values than other parameters for predicting mortality with the best cutoff value of 132 × 109/L, followed by WBC with the optimal cutoff value of 6.15 × 109/L. Multivariable Cox regression analysis showed platelet and WBC were independent prognostic factors for predicting mortality. Low platelet group showed lower survival according to Kaplan-Meier method. CONCLUSIONS: In conclusion, the levels of platelet and WBC on the day of sepsis onset are valuable indicators for predicting mortality in neonates with sepsis.

Development of a prognostic nomogram for patients with malignant mesothelioma with bone metastasis.

Malignant mesothelioma (MM) is a rare aggressive tumor, and bone metastasis often occurs in later stages of this disease. This study aimed to establish a nomogram to predict the prognosis of bone metastasis of patients with MM. Data from the Surveillance, Epidemiology, and End Results database were screened and retrieved. This study included 311 patients with MM with bone metastases. Prognostic factors were analyzed using the Kaplan-Meier method and Cox proportional hazards model. A nomogram for overall survival (OS) was established and evaluated using statistically significant prognostic factors, and cancer-specific survival (CSS) analysis was performed to investigate its prognostic factors. In addition, the metastasis patterns of patients with MM were investigated, and the effects of different sites of metastasis on survival were compared using the Kaplan-Meier method. Age, sex, histological type, and chemotherapy were identified as the independent risk factors for OS. The 1-, 2-, and 3-year areas under the curve of the nomogram were 0.792, 0.774, and 0.928, and 0.742, 0.733, and 0.733 in the training and validation sets, respectively. Compared to OS, histological type, radiotherapy, and chemotherapy were independent risk factors for CSS. Different metastatic sites in MM have significantly different effects on prognosis.

The Clinical Characteristic and Management of Patients with Nocardiosis in a Tertiary Hospital in China.

Nocardiosis is an uncommon opportunistic bacterial infection which becomes a significant health problem due to its increasing incidence and high mortality rate. However, many nocardiosis patients are underdiagnosed by physicians. To summarize the clinical characteristics and management of nocardiosis would help with better diagnosis and prognosis of nocardiosis. This retrospective study was conducted based on the medical records of nocardiosis patients between January 2015 and December 2021 in a tertiary hospital in China. Overall, 44 nocardiosis patients with 54 specimens were included. The patients consisted of 26 males and 18 females with a mean age of 50.4 ± 13.2 years. Among 44 patients, 26 (59.1%) were previously given immunosuppressive therapy. Connective tissue diseases (CTDs) were the most common underlying disease (16/44). The most frequent infection sites were the lungs (17/44) and skin or soft tissues (8/44). Common symptoms included cough (23/44), expectoration (18/44), fever (15/44), and subcutaneous abscesses (15/44). Forty-five out of 54 specimens (83.3%) required over 48 hours of culture time for nocardiosis detection. Thirty-six patients were cured or improved, 5 patients were discharged from the hospital due to poor prognosis, and 1 patient died. The average diagnosis time of poor prognosis cases was 19.7 days, which was significantly longer than those of improved or cured patients (7.3 days). Immunosuppressed patients comprise a large part of nocardiosis cases, which is worth attention in clinical practice. Early diagnosis, specifically through prolonged cultivation time of specimen, could help achieve better prognosis of nocardiosis patients.

Early-life prophylactic antibiotic treatment disturbs the stability of the gut microbiota and increases susceptibility to H9N2 AIV in chicks.

BACKGROUND: Antibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment. RESULTS: Unexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection. CONCLUSIONS: Our data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management. Video Abstract.

Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals.

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.

Clinically Applicable Homogeneous Assay for Serological Diagnosis of Alpha-Fetoprotein by Impact Electrochemistry.

Tumor protein quantification with high specificity, sensitivity, and efficiency is of great significance to enable early diagnosis and effective treatment. The existing methods for protein analysis usually suffer from high cost, time-consuming operation, and insufficient sensitivity, making them not clinically friendly. In this work, a label-free homogeneous sensor based on the nano-impact electroanalytic (NIE) technique was proposed for the detection of tumor protein marker alpha-fetoprotein (AFP). The detection principle is based on the recovery of current of single PtNP catalyzed hydrazine oxidation due to the release of the pre-adsorbed passivating aptamers on PtNPs from the competition of the stronger binding between the specific interaction of the AFP aptamer and AFP. The intrinsic one-by-one analytical ability of NIE allows highly sensitive detection, which can be further improved by reducing the reaction/incubation volume. Meanwhile, the current sensor avoids a laborious labeling procedure as well as the separation and washing steps due to the in situ characteristic of NIE. Accordingly, the current sensor enables efficient, highly sensitive, and specific AFP analysis. More importantly, the reliable detection of AFP in diluted real sera from hepatocellular carcinoma (HCC) patients is successfully achieved, indicating that the impact electrochemistry-based sensing platform has great potential to be applied in point-of-care devices for HCC liquid biopsy.