BACKGROUND:The plasmid-mediated tigecycline resistance gene tmexCD-toprJ has emerged in clinical and animal isolates, but its epidemiological spread and plasmid adaptation mechanisms remain unclear. METHODS:We characterized tmexCD-toprJ-carrying plasmids from the PLSDB database through comprehensive bioinformatic analyses, revealing their genetic features and potential inter-species transmission routes. RESULTS:Genomic analysis of 197 tmexCD-toprJ-carrying plasmids revealed significant backbone diversity, clustering into 18 groups and 12 singletons. The 30 identified host species were predominantly Klebsiella pneumoniae (K. pneumoniae) (53.3%), followed by Pseudomonas aeruginosa (P. aeruginosa) (16.8%) and Klebsiella quasipneumoniae (K. quasipneumoniae) (4.1%). MOB-suite typing classified 53.8% as conjugative, 5.6% mobilizable and 40.61% non-mobilizable. Over half of the tmexCD-toprJ-carrying plasmids were predicted to contain the MOBH family. Among the identified variants, tmexCD1-toprJ1, tmexCD2-toprJ2 and tmexCD3-toprJ1 representing the predominant forms. TmexCD1-toprJ1 was linked to IncFIB/IncHI1B/rep_cluster_1254 plasmids, while tmexCD2-toprJ2 associated with diverse replicons, enabling cross-species spread. A total of 14 plasmids co-localized tmexCD-toprJ with carbapenemase (blaNDM/KPC) and mcr genes, forming high-risk resistance platforms. Notably, a 36 483 bp insertion in IncP/rep_cluster_1115 plasmids disrupted tmexC6D6-toprJ1b and carried heavy metal resistance genes. CONCLUSIONS:These findings enhance our understanding of the diversity of tmexCD-toprJ-carrying plasmids. The convergence of tmexCD-toprJ with carbapenemase and polymyxin resistance genes in clinically prevalent plasmids underscores an urgent need for enhanced surveillance targeting complete genetic environments.

Background: Biting midges are important medical and veterinary vectorinsects that can transmit a range of zoonotic viruses. The Beijing-Tianjin-Hebei (BTH) region, as the core area in northern China, is rich in tourism resources, but the characteristics of the virome of biting midges in this region remain unclear. Results: A total of 12152 biting midgesindividuals were collected, and 7 species of Culicoides were identified. Culicoides punctatus (67.02%) and Culicoides morisitai (19.01%) were the dominant species. Metatranscriptomic sequencing yielded 9.79 billion reads, which were assembled into 19472821 contigs, with 45369 annotated viral sequences. Virome analysis showed that RNA viruses predominated, and positive-sense single-stranded RNA ((+)ssRNA)viruses accounted for the highest proportion. Geographic and host species factors significantly affected the viral composition (PERMANOVA, P<0.05). Phylogenetic analysis identified 22 virus species with 208 sequences, including 4 known viruses and 18 potential novel viruses, among which arbovirusessuch as Gouleako virus are worthy of attention. Conclusion: This study is the first to systematically reveal the diversity characteristics of the Culicoides virome in the BTH region and discover a variety of potential novel viruses, which provides an important scientific basis for the monitoring and prevention of regional arboviruses. The results emphasize the ecological importance of Culicoides as virus hosts, suggesting the need to strengthen ongoing monitoring of vector-borne viruses in this region.

Biting midges are important medical and veterinary vector insects that can transmit a range of zoonotic viruses. The Beijing-Tianjin-Hebei (BTH) region, as the core area in northern China, is rich in tourism resources, but the characteristics of the virome of biting midges in this region remain unclear. A total of 12,152 biting midges individuals were collected, and 7 species of Culicoides were identified. Culicoides punctatus (67.02

Background Klebsiella pneumoniae ( K. pneumoniae ) poses critical therapeutic challenges due to multidrug resistance (MDR). While antibiotic resistance genes (ARGs) are primary determinants, their expression and phenotypic impact are modulated by mobile genetic elements such as insertion sequence (IS) elements. However, the contribution of IS elements to antimicrobial resistance (AMR) prediction remains largely unexplored in K. pneumoniae . Methods We retrieved genome sequences and corresponding antimicrobial susceptibility phenotypes for 2,732 K. pneumoniae isolates from the PATRIC database (2004–2024). We evaluated ARGs, IS elements, IS-ARG pairs, and curated key feature sets using six machine learning (ML) algorithms to predict resistance phenotypes for 15 antibiotics. Model performance was assessed using accuracy, recall, positive predictive value (PPV), F1-score, and the area under the receiver operating characteristic (ROC) curve (AUC). SHAP analysis was employed to interpret feature contributions, and enrichment of ARGs and IS elements in key feature sets was examined. Hierarchical clustering based on IS-ARG co-occurrence patterns was performed to explore associations with MDR profiles. Results The Random Forest (RF) and Support Vector Machine (SVM) outperformed other models, achieving mean accuracies of 92.22% and 88.83% across all antibiotics. SVM utilizing the key feature set attained an AUC of 99.87% for trimethoprim. IS elements enabled RF to reach the highest per-antibiotic accuracy of 97.73% for levofloxacin, with additional accuracies of 94.28% for meropenem, 96.01% for amikacin, and 93.44% for trimethoprim-sulfamethoxazole. Models utilizing ARGs demonstrated superior overall performance over those employing IS elements, with a higher mean accuracy of 92.08% across all 15 antibiotics compared to 89.82%. IS elements were significantly enriched in key feature sets of all 15 drugs (fold change ≥ 2, P ≤ 0.05), with RF and SHAP analysis identifying specific IS elements (e.g., IS 1380 , IS 66 , IS 1182 ) as key predictors. IS-ARG co-occurrence analysis revealed 314 pairs, with IS 6 - bla SHV pairs accounting for 35.99%. Hierarchical clustering stratified isolates into seven clusters with distinct MDR profiles. Notably, IS 21 - bla KPC associations were linked to resistance against eight antimicrobials, while the absence of specific IS-ARG pairs correlated with resistance to ceftazidime, ciprofloxacin, and levofloxacin. Conclusions This study established the potential to improve predictive accuracy in ML models for specific antibiotics when utilizing IS elements as genomic features in K. pneumoniae , with RF and SVM achieving superior performance across multiple feature sets. IS elements served as critical predictors beyond ARGs, and their co-occurrence with ARGs was associated with MDR phenotypes. The identification of IS 21 - bla KPC as a marker of resistance to eight antibiotics and the stratification of isolates into clinically relevant clusters provided candidate targets for genomic surveillance. These findings demonstrate that integrating mobile genetic elements into resistance prediction frameworks improved both predictive accuracy and biological interpretability, offering novel biomarkers and mechanistic insights for resistance surveillance.

ObjectiveCarbapenem-resistant Klebsiella pneumoniae (CRKP) infection has become a global public health problem in recent years. However, ceftazidime-avibactam-resistant (CAZ/AVI-R) Klebsiella pneumoniae (K. pneumoniae) has emerged during treatment for CRKP infection. Therefore, understanding the molecular epidemiological characteristics and resistance-related mutations of global CAZ/AVI-R K. pneumoniae strains is crucial for guiding the rational use of CAZ/AVI and for implementing the control measures to prevent the spread of CAZ/AVI-R K. pneumoniae.MethodsNon-repetitive K. pneumoniae strains isolated from clinical and sewage samples from three hospitals were subjected to antimicrobial susceptibility testing (AST) and whole-genome sequencing (WGS). According to the E-test results, 37 and 11 CAZ/AVI-R K. pneumoniae strains were included from clinical and sewage samples, respectively. After applying the inclusion and exclusion criteria and carrying quality control, 253 CAZ/AVI-R K. pneumoniae strains with genome sequences were retrieved from public databases. Sequence types (STs) and serotypes were identified using Kleborate. Antimicrobial resistance genes (ARGs), virulence factors, and plasmids were annotated using Abricate. Insertion sequences (ISs), prophages, and macromolecular secretion systems were predicted using ISEScan, Dbscan, and Macsyfinder, respectively. Prokka, Roary, and IQtree2 were used for annotation, core gene alignment, and phylogenetic analysis, respectively. Mutations in outer membrane porins (OmpK35 and OmpK36) and efflux pumps (AcrA and AcrB) were analyzed and visualized using Miniprot and BioAider.ResultsA total of 301 CAZ/AVI-R K. pneumoniae strains were collected, comprising 37 human clinical strains, 11 sewage-derived strains, and 253 strains from public databases. Through comprehensive annotation, we identified 43 STs, 37 capsular (K) serotypes, 5 O antigen serotypes, 27 plasmid types and 22 ISs, 135 virulence genes, and 10 macromolecular secretion systems were annotated. Prophages carrying ARGs were annotated in 106 strains. The phylogenetic tree was roughly divided into 10 clades based on porins mutations, ARGs, virulence scores, and plasmid types. In total, 128 distinct ARGs were identified among the 301 strains. The ARGs associated with CAZ/AVI resistance in K. pneumoniae strains mainly included the class B metallo-beta-lactamases (MBLs) genes, blaKPC-2, and blaKPC-3 variants. Analysis of porin mutations revealed that in OmpK35, the most common substitution among all strains from three collection sources was at position 28 (*aaK). OmpK36 exhibited the highest number of mutations among strains from three sources, with frequent changes at position 136 (T136G), 137 (-gacacc), and 349 (H349R). Some porin mutations were identified exclusively in strains isolated from hospital clinical samples by our research team. OmpK35 had a substitution at position 132 (E132K). OmpK36 had substitutions at positions 2 (K2S), 3 (V3L), and 146 (R146H), respectively. AcrA and AcrB had substitutions at positions 188 (T188A) and 716 (R716L), respectively. Among the 301 strains, the majority had multiple drug resistance-related mutations, which were extensively distributed across 10 different clades.ConclusionThe combination of multiple drug resistance-related mutations leads to resistance to CAZ/AVI. The most common resistance-related mutations in strains from both public databases and those collected by our team are the coexistence of outer membrane porins and efflux pump mutations, and carriage of MBLs genes.

Group B Streptococcus (GBS) causes severe neonatal infections, leading to high mortality rates. This study aimed to investigate the genetic characteristics of GBS isolates in a hospital setting. Nineteen isolates were identified through a review of preservation and cultivation processes since January 2022, followed by antibiotic susceptibility testing. Whole-genome sequencing (WGS) was used to investigate genetic relationships. Among 19 isolates, serotype V was the most prevalent (n = 7), followed by Ib (n = 6) and III (n = 6). Genomic sequence analysis revealed that 19 isolates belonged to four sequence types (STs) related to four clonal complexes (CCs), namely CC12, CC19, CC327, and CC452. The isolates exhibited high resistance rates to erythromycin (89 %, n = 17), levofloxacin (79 %, n = 15), clindamycin (68 %, n = 13), and tetracycline (53 %, n = 10). The mreA gene was found in all GBS isolates (100 %), while the most prevalent resistance gene was ermB (84 %). Furthermore, the fbsB virulence gene associated with adherence was identified in four serotype V/ST890 GBS isolates. Two isolates with different sequence types (ST10, ST19) were found to have undergone parallel mutations in the gene SE858_09425, which encodes a DNA translocase FtsK. Both exhibited an I259L substitution in a conserved ligand-binding domain, strongly suggesting this site is critical for adaptive evolution. IMPORTANCE: Group B Streptococcus (GBS) is a major pathogen causing severe neonatal infections, such as sepsis and meningitis, with high mortality and morbidity rates. The rising antimicrobial resistance of GBS presents significant challenges for clinical management. This study investigates 19 GBS isolates isolated from neonates in Qingyang, Gansu, focusing on their genetic characteristics and resistance profiles through molecular epidemiological analysis and WGS. The findings offer critical insights into the molecular mechanisms of GBS infections, which can inform infection control measures, improve prevention strategies, and optimize antimicrobial therapies to enhance neonatal healthcare outcomes.

In 2024, a S. aureus foodborne illness outbreak in Hebei Province, China, affected 61 out of 563 individuals (10.84 % prevalence), causing symptoms like diarrhea, vomiting, abdominal pain, and nausea. A case-control study implicated ròujiámó, a breakfast item, as the suspected vehicle (OR = 34.81, 95 % CI: 2.07-585.30, P < 0.001). Laboratory analyses identified S. aureus in samples collected from patients, kitchen workers, food, and the environment. Three strains, belonging to ST6 and spa type t701, were isolated and characterized. They showed resistance to penicillin, harbored many virulence genes including sea, and clustered closely in phylogenetic analysis. Notably, the sea gene was located on an intact prophage element that may enhance its pathogenic potential and pose new clinical challenges. The outbreak was due to S. aureus contamination in ròujiámó caused by unsafe kitchen practices. Improved food safety supervision and worker education are needed to prevent future outbreaks.

Background: Thyroid eye disease (TED) is a common autoimmune inflammatory disease that significantly impairs quality of life. Mitochondrial metabolism is a key driver for the pathogenesis of inflammatory diseases, yet its role in TED remains poorly understood. Our study aimed to investigate the mechanisms by which mitochondrial metabolism contributes to TED and identify potential treatment targets using a multi-methodological approach. Methods: We performed a series of bioinformatics analyses, including the identification of differentially expressed genes (DEGs), Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration assessments, genome-wide association studies (GWAS), and machine learning. Results: By integrating the datasets GSE58331, GSE105149, and GSE185952, we ultimately screened 14 mitochondria-related (DEGs) from TED samples and applied machine learning to select diagnostic markers. 3 disease-associated diagnostic biomarkers (Ifi27, Cyba, and Cmpk2) were identified. Immune cell infiltration analysis revealed 4 immune cell types significantly associated with TED: follicular helper T (Tfh) cells, monocytes, M1 macrophages, and neutrophils. Multiple specific correlations were observed between these immune cells and the diagnostic biomarkers. Conclusion: We identified a unique mitochondrial-related genetic signature essential for TED progression, which provides valuable insights into immune infiltration. These findings may advance molecular research on TED and offer novel strategies and therapeutic approaches for this condition.

Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a type of zoonoses withwidespread distribution. In 2019, a case of Q fever was diagnosed by metagenomic next-generation sequencing (mNGS) method in Xuyi County (Jiangsu province, China). The seroprevalence of previous fever patients and the molecular epidemiology of Coxiella in wild hedgehogs and harbouring ticks around the confirmed patient were detected to reveal the genetic characteristics and pathogenicity of the Coxiella strains. Four of the 90 serum samples (4.44%) were positive for specific C. burnetii IgM antibody, suggesting that local humans are at risk of Q fever. The positive rates of C. burnetii in hedgehogs and ticks were 21.9% (7/32) and 70.5% (122/173), respectively. At least 3 strains of Coxiella were found prevalent in the investigated area, including one new genotype of pathogenic C. burnetii (XYHT29) and two non-pathogenic Coxiella-like organisms (XYHT19 and XYHT3). XYHT29 carried by ticks and wild hedgehogs successfully infected mice, imposing a potential threat to local humans. XYHT19, a novel Coxiella-like microorganism, was first discovered in the world to co-infect with C. burnetii in Haemaphysalis flava. The study provided significant epidemic information that could be used for prevention and control strategies against Q fever for local public health departments and medical institutions.

Purpose: This study aimed to propose a fully automatic eyelid measurement system and compare the contours of both the upper and lower eyelids of normal individuals according to age and gender. Design:Prospective study. Participants: Five hundred and forty healthy Chinese aged 0 to 79 years in a tertiary hospital were included. Methods: Facial images in the primary gazing position were used to train and test the proposed automatic system for eye recognition and eye segmentation. According to the 10-millimeter diameter circular marker, measurements were transformed from pixel sizes into factual distances. Main Outcome Measures: Midpupil lid distances (MPLDs) every 15 degrees of all participants were automatically measured in both genders (30 males and 30 females in each age group) by the proposed deep learning (DL)based system. Intraclass correlation coefficients (ICCs) were performed to assess the agreement between the automatic and manual margin reflex distances (MRDs). The eyelid contour, eyelid asymmetry, and palpebral fissure obliquity were analyzed using MPLD, temporal-versus-nasal MPLD ratio, and the angle between the inner and outer canthi, respectively. Results: The measurement of MRDs by the automatic system excellently agreed with that of the expert, with ICCs ranging from 0.863 to 0.886. As the age of the participants increased, the values of MPLDs reached a peak in those in their 20s or 30s and then gradually decreased at all angles. The temporal sector showed greater changes in MPLDs than the nasal sector, and the changes were more significant in females than in males. The maximum value of palpebral fissure obliquity appeared before 10 years in both genders and remained relatively stable after the 20s (P > 0.05). Conclusions: The proposed DL-based eyelid analysis system allowed automatic, accurate, and comprehensive measurement of the eyelid contour. The refinement of eyelid shape quantification could be beneficial for future objective assessment preocular and postocular plastic surgery.

Prosthetic eye is indispensable as filler after enucleation in patients with anophthalmia, whereas there are still many complications including postoperative infection and eye socket depression or extrusion during the conventional artificial eye material applications. Some Ca-silicate biomaterials showed superior bioactivity but their biological stability in vivo limit the biomedical application as long-term or permanent implants. Herein we aimed to understand the physicochemical and potential biological responses of zinc doping in wollastonite bioceramic used for orbital implants. The wollastonite powders with different zinc dopant contents (CSi-Znx) could be fabricated as porous implants with strut or curve surface pore geometries (cubic, IWP) via ceramic stereolithography. The experimental results indicated that, by increasing zinc-substituting-Ca ratio (up to 9%), the sintering and mechanical properties could be significantly enhanced, and meanwhile the bio-dissolution in vitro and biodegradability in vivo were thoroughly inhibited. In particular, an appreciable angiogenic activity and expected antibacterial efficacy (over 90 %) were synergistically achieved at 9 mol% Zn dopant. In the back-embedding and enucleation and implantation model experiments in rabbits, the superior continuous angiogenesis was corroborated from the 2D/3D fibrovascular reconstruction in the IWP-pore CSi–Zn9 and CSi–Zn13.5 groups within very short time stages. Totally, the present silicate-based bioceramic via selective Zn doping could produce outstanding structural stability and bifunctional biological responses which is especially valuable for developing the next-generation implants with vascular insertion and fixation in orbital reconstruction prothesis.

Background:Klebsiella michiganensis is an emerging human pathogen that causes nosocomial infections. Its prevalence and spread in the environment should not be ignored. This study identified and characterized Klebsiella michiganensis co-harboring bla KPC-2 and TmexCD2-ToprJ2 in hospital wastewater samples. Methods:Twelve K. michiganensis strains were isolated from wastewater samples collected at a tertiary hospital in Beijing, China. The genomic characteristics of K. michiganensis strains were analyzed using whole-genome sequences, providing information on the comparison between the genome of K. michiganensis strains and the reference genome, antibiotic resistance genes (ARGs), virulence genes, secretion systems, and mobile genetic elements (plasmids, insertion sequences [ISs], and prophages). Results:Genome analysis showed that the twelve multi-drug resistant (MDR) strains carried a variety of ARGs and virulence genes, as well as four macromolecular secretion systems (T1SS, T2SS, T5aSS, T5bSS, and T4aP). The genetic environments of both the TmexCD2-ToprJ2 gene cluster and bla KPC-2 gene contained ISs. The plasmids carrying TmexCD2-ToprJ2 gene cluster of nine strains in clade 1 and two strains in clade 2 were annotated as IncR plasmid and rep_cluster_1254 type, respectively. The plasmids carrying bla KPC-2 in 10 strains in clade 1 were identified as IncU, and the plasmids carrying bla KPC-2 in the k11 and k12 strains in clade 2 were IncU and IncX6. The phylogenetic tree and heatmap revealed that the secretion system of type VI (T6SSi) existed in 10 strains in clade 1, and Type IV (T4SS) only existed in the k11 strain in clade 2. In addition, K. michiganensis strains carried 13 plasmids, 14 ISs, and 138 prophages. Conclusion:In this study, the whole genome sequencing demonstrated the diversity of K. michiganensis genome despite 12 K. michiganensis strains from a hospital wastewater, which lays the foundation for further genetic research and drug resistance gene transmission.

PURPOSE:Segmentation of orbital tumors in CT images is of great significance for orbital tumor diagnosis, which is one of the most prevalent diseases of the eye. However, the large variety of tumor sizes and shapes makes the segmentation task very challenging, especially when the available annotation data is limited. METHODS:To this end, in this paper, we propose a multi-scale consistent self-training network (MSCINet) for semi-supervised orbital tumor segmentation. Specifically, we exploit the semantic-invariance features by enforcing the consistency between the predictions of different scales of the same image to make the model more robust to size variation. Moreover, we incorporate a new self-training strategy, which adopts iterative training with an uncertainty filtering mechanism to filter the pseudo-labels generated by the model, to eliminate the accumulation of pseudo-label error predictions and increase the generalization of the model. RESULTS:For evaluation, we have built two datasets, the orbital tumor binary segmentation dataset (Orbtum-B) and the orbital multi-organ segmentation dataset (Orbtum-M). Experimental results on these two datasets show that our proposed method can both achieve state-of-the-art performance. In our datasets, there are a total of 55 patients containing 602 2D images. CONCLUSION:In this paper, we develop a new semi-supervised segmentation method for orbital tumors, which is designed for the characteristics of orbital tumors and exhibits excellent performance compared to previous semi-supervised algorithms.

Losing an eye to various reasons at any age may have a major impact on one 's self-image, except for requiring to adapt monocular vision. The conventional metal oxide or polymer implants for orbital reconstruction, involving the vulnerable postoperative administration (migration, exposure), are always challenged due to deficiency of some critical efficacy attainability. While coralline hydroxyapatite ceramics offer alternatives, they come with the insufficient infection prevention and tailor-made manufacture. This underscores the insistent need for personized multifunctional orbital materials. In this context, the functional orbital implants are emerging as a promising solution for orbital reconstruction, especially accompanying with self -antibacterial and sufficient integration with host tissue. Herein we developed the porous Ca-Zn-silicate bioceramic implants to seamlessly adapt to the clinical tailor-made requirements. Our study introduced the dilute magnesium dopant into hardystonite (Ca 2 ZnSi 2 O 7 ; HT) bioceramic and fabricated precisely tuning gradient pore architectures (Triply radial structures) via digital light processing technique. Notably, benefiting from its gradient pore topologies and chemical compositions, our investigations unveiled the proposed HT -based implants containing 4 %Mg substitution yielded desirable surface reactivity, affording prominent anti-inflammatory and antibacterial properties and rapid vascularization (within 2 weeks after implantation), in comparison to the clinically available polymeric or bioceramic products (MEDPOR (R) & Hydroxyapatite (R)). Beyond this, our multifunctional implants exhibited exceptional structural stability and biocompatibility in vitro and in vivo . Given these impressive attributes, our findings hold promising potential in revolutionizing the field of orbital reconstruction medicine, offering the next -generation advanced silicate bioceramics for crafting personizing and precise implantation strategy.

Klebsiella michiganensis is an increasingly important bacterial pathogen causing nosocomial infections in clinical patients. In this study, we described the molecular and genomic characteristics of a carbapenem-resistant K. michiganensis strain KM166 cultured from a one-month premature baby's blood sample. KM166 showed lower biofilm forming ability in optical density (OD) than K. pneumoniae NTUH-K2044 (0.271 ± 0.027 vs. 0.595 ± 0.054, p = 0.001), and the median lethal dose (0.684 lg CFU/mL) was lower than K. pneumoniae strain NTUH-K2044 (6.679 lg CFU/mL). A IncFII/IncFIA(HI1)/IncFIB(K) multiple replicon plasmid in KM166 was identified carrying three replicon types. It has low homology to Escherichia coli pMRY09-581ECO_1 and the highest homology similarity to the INcFIA/INcFII(p14)-type plasmid in K. michiganensis strain fxq plasmid pB_KPC, suggesting that this multiple replicon plasmid was unlikely to have been transmitted from E. coli and probably a transfer of repFIB replicon genes from other K. michiganensis strains into the INcFIA/INcFII(p14)-type plasmid of KM166 had occurred. Mapping of the gene environment revealed that bla KPC-2 in KM166 plasmid 3 had high identity and same Tn3-tnpR-IS481-bla KPC-2-klcA_1 genomic context structure with K. pneumoniae strain JKP55, plasmid pKPC-J5501, and bla KPC-2-carrying plasmid proved to be autonomously transferred under the help of mobile genetic elements into Escherichia coli 600 by plasmid conjugation experiment. In conclusion, we have characterized a K. michiganensis strain carrying multi-replicon IncFII/IncFIA(HI1)/IncFIB(K) plasmid and bla KPC-2-carrying IncFII(p14)/IncFIA plasmid in this study, which provided insights about the evolutionary diversity of plasmids carried by K. michiganensis.

Hematophagous arthropods occupy a pivotal role in ecosystems, serving as vectors for a wide array of pathogens with significant implications for public health. Their capacity to harbor and transmit viruses through biting actions creates a substantial risk of zoonotic spillover. Despite the advancements in metagenomic approaches for virus discovery in vectors, the isolation and cultivation of viruses still pose significant challenges, thereby limiting comprehensive assessments of their pathogenicity. Here, we curated two datasets: one with 294 viruses, characterized by 37 epidemiological features, encompassing virus information and host associations; the second with 71,622 sequences of hematophagous arthropod vector-borne viruses, annotated with 33 sequence features. Two XGBoost models were developed to predict arbovirus human pathogenicity: one integrating macroscopic eco-epidemiological data, the other incorporating virus-related sequence features. The macroscopic model identified non-vector host transmission as a key determinant, especially involving Perissodactyla, Artiodactyla, and Carnivora Order. The sequence-based model demonstrated that viral adhesion and viral invasion had distinct trends with consistent increase and decrease in the likelihood of virus pathogenicity to humans, respectively. With validated through an independent dataset, the model exhibited a congruous alignment with documented pathogenicity outcomes. Together, the models offer a holistic framework for assessing the pathogenic potential of viruses transmitted by hematophagous arthropods.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThe laboratory conducting this research is funded by grants from the National Key Research and Development Program of China (2019YFC1200501).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe raw dataset supporting the findings of this study is available on Figshare at https://doi.org/10.6084/m9.figshare.22154573.v5. Additionally, the processed data used and/or analyzed during the current study can be obtained by contacting the corresponding author. Requests for access to the processed data will be promptly addressed.

目的:中重度甲状腺相关眼病内下壁骨性减压联合脂肪减压术的临床疗效观察.方法:回顾性分析25例(31眼)在浙江大学医学院附属第二医院眼科行内下壁骨性减压联合脂肪减压术治疗的甲状腺相关眼病患者,观察时间为2020年1月至2022年1月.术前所有患者均进行了眼眶CT检查,并对双眼视力、眼球突出、复视及双眼外观形态进行了测量.手术效果评价指标为:术后眼球突出度、视力和复视程度,并对相关数据进行统计和分析.结果:术后眼球突出度回退2～6 mm,平均回退(3.45±0.93)mm,切除眶内脂肪1.4～3.6 mL,平均切除(2.33±0.66)mL,外观恢复满意.4例患者术前存在复视,2例患者术后新发复视,术前已存在复视的患者,术后复视程度并未加重,新发的2例复视患者均为轻度复视.术后CT检查显示眼眶减压效果良好.结论:内下壁骨性减压与脂肪减压术联合,可以有效扩大眼眶容积,对眼球进行回纳,减少眼球突出程度,改善容貌外观,且手术切口隐蔽美观,具有较好的临床疗效果.

Determining the nature of orbital tumors is challenging for current imaging interpretation methods, which hinders timely treatment. This study aimed to propose an end-to-end deep learning system to automatically diagnose orbital tumors. A multi-center dataset of 602 non-contrast-enhanced computed tomography (CT) images were prepared. After image annotation and preprocessing, the CT images were used to train and test the deep learning (DL) model for the following two stages: orbital tumor segmentation and classification. The performance on the testing set was compared with the assessment of three ophthalmologists. For tumor segmentation, the model achieved a satisfactory performance, with an average dice similarity coefficient of 0.89. The classification model had an accuracy of 86.96%, a sensitivity of 80.00%, and a specificity of 94.12%. The area under the receiver operating characteristics curve (AUC) of the 10-fold cross-validation ranged from 0.8439 to 0.9546. There was no significant difference on diagnostic performance of the DL-based system and three ophthalmologists (p > 0.05). The proposed end-to-end deep learning system could deliver accurate segmentation and diagnosis of orbital tumors based on noninvasive CT images. Its effectiveness and independence from human interaction allow the potential for tumor screening in the orbit and other parts of the body.

Introduction:Hypermucoviscous Klebsiella pneumoniae (HmKp) poses an emerging and highly pathogenic global health threat. This study aimed to investigate the clinical and genomic characteristics of HmKp isolates to better understand the virulence mechanisms of the hypermucoviscous (HMV) phenotype.Methods:From May 2018 to August 2021, 203 non-repeat K. pneumoniae isolates causing invasive infections were collected from a hospital in Beijing, China. Isolates were divided into HmKp (n=90, 44.3%) and non-HmKp (n=113, 55.7%) groups according to string test results.Results:Multivariate regression showed that diabetes mellitus (odds ratio [OR]=2.20, 95% confidence interval (CI): 1.20-4.05, p=0.010) and liver abscess (OR=2.93, CI 95%:1.29-7.03, p=0.012) were associated with HmKp infections. K. pneumoniae was highly diverse, comprising 87 sequence types (STs) and 54 serotypes. Among HmKp isolates, ST23 was the most frequent ST (25/90, 27.8%), and the most prevalent serotypes were KL2 (31/90, 34.4%) and KL1 (27/90, 30.0%). Thirteen virulence genes were located on the capsular polysaccharide synthesis region of KL1 strains. HmKp isolates were sensitive to multiple antibiotics but carried more SHV-type extended spectrum β-lactamase (ESBL) resistance genes (p<0.05), suggesting that the emergence of ESBL-mediated multidrug resistance in HmKp should be monitored carefully during treatment. Phylogenetic analysis disclosed that HmKp isolates were highly diverse. Comparative genomic analysis confirmed that the HMV phenotype is a plasmid-encoded virulence factor. Seventeen HmKp genes were highly associated with HmKp, and included rmpAC, 7 iron-acquisition-related genes, and pagO, which may promote liver abscess formation.Discussion:This investigation provides insight into the mechanisms producing the HMV phenotype.

Mosquitoes and biting Culicoides species are arbovirus vectors. Effective virome profile surveillance is essential for the prevention and control of insect-borne diseases. From June to September 2021, we collected eight species of female mosquito and Culicoides on Zhoushan Island, China, and used meta-viromic sequencing to analyze their virome compositions and characteristics. The classified virus reads were distributed in 191 genera in 66 families. The virus sequences in mosquitoes with the largest proportions were Iflaviridae (30.03%), Phasmaviridae (23.09%), Xinmoviridae (21.82%), Flaviviridae (13.44%), and Rhabdoviridae (8.40%). Single-strand RNA+ viruses formed the largest proportions of viruses in all samples. Blood meals indicated that blood-sucking mosquito hosts were mainly chicken, duck, pig, and human, broadly consistent with the habitats where the mosquitoes were collected. Novel viruses of the Orthobunyavirus, Narnavirus, and Iflavirus genera were found in Culicoides by de-novo assembly. The viruses with vertebrate hosts carried by mosquitoes and Culicoides also varied widely. The analysis of unclassified viruses and deep-learning analysis of the "dark matter" in the meta-viromic sequencing data revealed the presence of a large number of unknown viruses. IMPORTANCE The monitoring of the viromes of mosquitoes and Culicoides, widely distributed arbovirus transmission vectors, is crucial to evaluate the risk of infectious disease transmission. In this study, the compositions of the viromes of mosquitoes and Culicoides on Zhoushan Island varied widely and were related mainly to the host species, with different host species having different core viromes. and many unknown sequences in the Culicoides viromes remain to be annotated, suggesting the presence of a large number of unknown viruses.