YBX1 promotes stemness and cisplatin insensitivity in intrahepatic cholangiocarcinoma via the AKT/ß-catenin axis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y-box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. METHODS: Three bulk and single-cell RNA-seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ß-catenin pathways. RESULTS: YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy-non-responsive ICC tissues. The YBX1-high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness-related pathways. Moreover, YBX1 expression is significantly correlated with several stemness-related genes (SOX9, OCT4, CD133, CD44 and EPCAM). Additionally, YBX1 overexpression significantly enhanced the colony- and spheroid-forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ß-catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ß-catenin axis. CONCLUSIONS: YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ß-catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

Bringing the Animal QTLdb and CorrDB into the future: meeting new challenges and providing updated services.

The Animal QTLdb (https://www.animalgenome.org/QTLdb) and CorrDB (https://www.animalgenome.org/CorrDB) are unique resources for livestock animal genetics and genomics research which have been used extensively by the international livestock genome research community. This is largely due to the active development of the databases over the years to keep up with the rapid advancement of genome sciences. The ongoing development has ensured that these databases provide researchers not only with continually updated data but also with new web tools to disseminate the data. Through our continued efforts, the databases have evolved from the original Pig QTLdb for cross-experiment QTL data comparisons to an Animal QTLdb hosting 220 401 QTL, SNP association and eQTL data linking phenotype to genotype for 2210 traits. In addition, there are 23 552 correlations for 866 traits and 4273 heritability data on 1069 traits in CorrDB. All these data were curated from 3157 publications that cover seven livestock species. Along with the continued data curation, new species, additional genome builds, and new functions and features have been built into the databases as well. Standardized procedures to support data mapping on multiple species/genome builds and the ability to browse data based on linked ontology terms are highlights of the recent developments.

High Cytomegalovirus Viral Load Is Associated With 182-Day All-Cause Mortality in Hospitalized People With Human Immunodeficiency Virus.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with increased mortality in persons with HIV (PWH). It is less clear whether CMV infection is still associated with mortality when routinely screened and adequately treated. METHODS: This retrospective cohort study recruited 1003 hospitalized adults with HIV with CD4 cell counts <200 cells/µL from May 2017 to June 2021. Blood CMV DNA was routinely measured and CMV DNAemia was treated if end-organ disease occurred. CMV viral load was categorized into below the limit of quantification (BLQ; <500 IU/mL), low viral load (LVL; 500-10 000 IU/mL), and high viral load (HVL; ≥10 000 IU/mL) groups. We compared the 182-day all-cause mortality among different groups. RESULTS: The median (IQR) CD4 cell count of patients was 33 (13-84) cells/µL. The prevalence of CMV DNAemia was 39.8% (95% CI: 36.7-42.9%) and was significantly associated with CD4 cell count. The 182-day all-cause mortality was 9.9% (95% CI: 8.0-11.7%). Univariable analysis showed that, compared with BLQ, LVL and HVL were associated with 1.73-fold and 3.81-fold increased risks of mortality, respectively (P = .032 and P < .001). After adjustment for predefined confounding factors, HVL but not LVL was still associated with increased risk of mortality (adjusted hazard ratio: 2.63; 95% CI: 1.61-4.29; P < .001). However, for patients on effective antiretroviral therapy, the impact of HVL on 182-day mortality was not significant (P = .713). CONCLUSIONS: High CMV viral load in hospitalized PWH was associated with higher mortality, even when identified early by screening. Optimalization of the management for those patients needs to be explored in future studies.

The Comparison of Surgical Margins and Type of Hepatic Resection for Hepatocellular Carcinoma With Microvascular Invasion.

OBJECTIVE: The objective of this study was to investigate the impact of surgical margin and hepatic resection on prognosis and compare their importance on prognosis in patients with hepatocellular carcinoma (HCC). METHODS: The clinical data of 906 patients with HCC who underwent hepatic resection in our hospital from January 2013 to January 2015 were collected retrospectively. All patients were divided into anatomical resection (AR) (n = 234) and nonanatomical resection (NAR) group (n = 672) according to type of hepatic resection. The effects of AR and NAR and wide and narrow margins on overall survival (OS) and time to recurrence (TTR) were analyzed. RESULTS: In all patients, narrow margin (1.560, 1.278-1.904; 1.387, 1.174-1.639) is an independent risk factor for OS and TTR, and NAR is not. Subgroup analysis showed that narrow margins (2.307, 1.699-3.132; 1.884, 1.439-2.468), and NAR (1.481, 1.047-2.095; 1.372, 1.012-1.860) are independent risk factors for OS and TTR in patients with microvascular invasion (MVI)-positive. Further analysis showed that for patients with MVI-positive HCC, NAR with wide margins was a protective factor for OS and TTR compared to AR with narrow margins (0.618, 0.396-0.965; 0.662, 0.448-0.978). The 1, 3, and 5 years OS and TTR rate of the two group were 81%, 49%, 29% versus 89%, 64%, 49% (P = .008) and 42%, 79%, 89% versus 32%, 58%, 74% (P = .024), respectively. CONCLUSIONS: For patients with MVI-positive HCC, AR and wide margins were protective factors for prognosis. However, wide margins are more important than AR on prognosis. In the clinical setting, if the wide margins and AR cannot be ensured at the same time, the wide margins should be ensured first.

Impact of inactivated COVID-19 vaccines on lung injury in B.1.617.2 (Delta) variant-infected patients.

BACKGROUND: Chest computerized tomography (CT) scan is an important strategy that quantifies the severity of COVID-19 pneumonia. To what extent inactivated COVID-19 vaccines could impact the COVID-19 pneumonia on chest CT is not clear. METHODS: This study recruited 357 SARS-COV-2 B.1.617.2 (Delta) variant-infected patients admitted to the Second Hospital of Nanjing from July to August 2021. An artificial intelligence-assisted CT imaging system was used to quantify the severity of COVID-19 pneumonia. We compared the volume of infection (VOI), percentage of infection (POI) and chest CT scores among patients with different vaccination statuses. RESULTS: Of the 357 Delta variant-infected patients included for analysis, 105 were unvaccinated, 72 were partially vaccinated and 180 were fully vaccinated. Fully vaccination had the least lung injuries when quantified by VOI (median VOI of 222.4 cm3, 126.6 cm3 and 39.9 cm3 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001), POI (median POI of 7.60%, 3.55% and 1.20% in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001) and chest CT scores (median CT score of 8.00, 6.00 and 4.00 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001). After adjustment for age, sex, comorbidity, time from illness onset to hospitalization and viral load, fully vaccination but not partial vaccination was significantly associated with less lung injuries quantified by VOI {adjust coefficient[95%CI] for "full vaccination": - 106.10(- 167.30,44.89); p < 0.001}, POI {adjust coefficient[95%CI] for "full vaccination": - 3.88(- 5.96, - 1.79); p = 0.001} and chest CT scores {adjust coefficient[95%CI] for "full vaccination": - 1.81(- 2.72, - 0.91); p < 0.001}. The extent of reduction of pulmonary injuries was more profound in fully vaccinated patients with older age, having underlying diseases, and being female sex, as demonstrated by relatively larger absolute values of adjusted coefficients. Finally, even within the non-severe COVID-19 population, fully vaccinated patients were found to have less lung injuries. CONCLUSION: Fully vaccination but not partially vaccination could significantly protect lung injury manifested on chest CT. Our study provides additional evidence to encourage a full course of vaccination.

Building a livestock genetic and genomic information knowledgebase through integrative developments of Animal QTLdb and CorrDB.

Successful development of biological databases requires accommodation of the burgeoning amounts of data from high-throughput genomics pipelines. As the volume of curated data in Animal QTLdb (https://www.animalgenome.org/QTLdb) increases exponentially, the resulting challenges must be met with rapid infrastructure development to effectively accommodate abundant data curation and make metadata analysis more powerful. The development of Animal QTLdb and CorrDB for the past 15 years has provided valuable tools for researchers to utilize a wealth of phenotype/genotype data to study the genetic architecture of livestock traits. We have focused our efforts on data curation, improved data quality maintenance, new tool developments, and database co-developments, in order to provide convenient platforms for users to query and analyze data. The database currently has 158 499 QTL/associations, 10 482 correlations and 1977 heritability data as a result of an average 32% data increase per year. In addition, we have made >14 functional improvements or new tool implementations since our last report. Our ultimate goals of database development are to provide infrastructure for data collection, curation, and annotation, and more importantly, to support innovated data structure for new types of data mining, data reanalysis, and networked genetic analysis that lead to the generation of new knowledge.

A special symptom of olfactory dysfunction in coronavirus disease 2019: report of three cases.

Three patients of coronavirus disease (COVID-19) showed the symptoms of olfactory dysfunction. Clinical characteristics and treatment were retrospective analyzed. Olfactory disorders are uncommon symptoms of COVID-19 in China. Early diagnosis and intervention are keys to the recovery of olfactory disorders. Particular attention should be devoted to olfactory dysfunction.

Fulminant central nervous system varicella-zoster virus infection unexpectedly diagnosed by metagenomic next-generation sequencing in an HIV-infected patient: a case report.

BACKGROUND: Varicella-zoster virus (VZV) infection can be diagnosed clinically once classical rash occurs but the diagnosis is challenging when typical rash is absent. We reported a case of fulminant central nervous system (CNS) VZV infection in a human immunodeficiency virus (HIV)-infected patient without typical VZV-related rash. CNS VZV infection was unexpected identified by metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 28-year-old HIV-infected patient presented with neurological symptoms for 3 days. The patient, who was not suspected of VZV infection at admission, quickly progressed to deep coma during the first 24 h of hospitalization. An unbiased mNGS was performed on DNA extract from 300 µL cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 97,248 (out of 38,561,967) sequence reads uniquely aligned to the VZV genome, and these reads covered a high percentage (99.91%) of the VZV. Presence of VZV DNA in CSF was further verified by VZV-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed CNS VZV infection. CONCLUSIONS: This study suggests that mNGS may be a useful diagnostic tool for CNS VZV infection. As mNGS could identify all pathogens directly from CSF sample in a single run, it has the promise of strengthening our ability to diagnose CNS infections in HIV-infected patients.

Metagenomic next-generation sequencing as a diagnostic tool for toxoplasmic encephalitis.

BACKGROUND: More than 100 different pathogens can cause encephalitis. Testing of all the neurological pathogens by conventional methods can be difficult. Metagenomic next-generation sequencing (NGS) could identify the infectious agents in a target-independent manner. The role of this novel method in clinical diagnostic microbiology still needs to be evaluated. In present study, we used metagenomic NGS to search for an infectious etiology in a human immunodeficiency virus (HIV)-infected patient with lethally diffuse brain lesions. Sequences mapping to Toxoplasma gondii were unexpectedly detected. CASE PRESENTATION: A 31-year-old HIV-infected patient presented to hospital in a critical ill condition with a Glasgow coma scale score of 3. Brain magnetic resonance imaging showed diffuse brain abnormalities with contrast enhancement. Metagenomic NGS was performed on DNA extract from 300 µL patient's cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 65,357 sequence reads uniquely aligned to the Toxoplasma gondii genome. Presence of Toxoplasma gondii genome in CSF was further verified by Toxoplasma gondii-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed the diagnosis of toxoplasmic encephalitis. CONCLUSIONS: This study suggests that metagenomic NGS may be a useful diagnostic tool for toxoplasmic encephalitis. As metagenomic NGS is able to identify all pathogens in a single run, it may be a promising strategy to explore the clinical causative pathogens in central nervous system infections with atypical features.

Developmental progress and current status of the Animal QTLdb.

The Animal QTL Database (QTLdb; http://www.animalgenome.org/QTLdb) has undergone dramatic growth in recent years in terms of new data curated, data downloads and new functions and tools. We have focused our development efforts to cope with challenges arising from rapid growth of newly published data and end users' data demands, and to optimize data retrieval and analysis to facilitate users' research. Evidenced by the 27 releases in the past 11 years, the growth of the QTLdb has been phenomenal. Here we report our recent progress which is highlighted by addition of one new species, four new data types, four new user tools, a new API tool set, numerous new functions and capabilities added to the curator tool set, expansion of our data alliance partners and more than 20 other improvements. In this paper we present a summary of our progress to date and an outlook regarding future directions.

A case report of oesophageal schwannoma with thoracoscopic surgery.

Oesophageal schwannomas is a rare tumour and most commonly found incidentally or from diagnostic workup of dysphagia or dyspnoea. Most oesophageal schwannomas are benign and more frequently occurs in female than in the male. To date, <40 cases have been described in the English literature. In this study, we reported the case of a 57-year-old woman visited our hospital with the symptom of long-time dysphagia. A thoracic computed tomography demonstrated an upper oesophageal well marginated and homogeneous mass that adhered to the right wall of the oesophagus. Oesophageal endoscopy showed an extrinsic bulge 21 cm distal to the incisors with normal overlying mucosa. Strictly on a clinical and radiologic basis, this entity is impossible to definitively diagnose, the final diagnosis was based on histopathology and immunohistochemistry. Tumour cells stain positive for S100, a characteristic marker of Schwann cell. A minimally invasive thoracoscopic surgery was performed. The post-operative period was uneventful.

[Magnetic resonance imaging features of Cryptococcus infection in central nervous system in patients with AIDS].

OBJECTIVE: To investigate the magnetic resonance imaging (MRI) features of Cryptococcus infection in central nervous system patients with acquired immune deficiency syndrome (AIDS).
 Methods: The retrospective study on magnetic resonance imaging (MRI) and clinical data of cryptococcal meningitis (CM) was carried out between July 2011 and March 2017. These patients had not received anti-retroviral treatment. Patients with other specific or suspicious diseases in the central nervous system were not included in the analysis.
 Results: A total of 39 patients were included in the analysis, with CD4 cell counts of 13.0×106/L [(0-205)×106/L], and 94.9% (37/39) of patients with CD4 cell count <100×106/L. Of the 39 patients, 26 patients showed abnormal MRI signals in the brain, which were most frequently involved in the basal ganglia (20/26, 76.9%). The basal ganglia lesions showed dilated Virchow-Robin space (VRS)/gelatinous spseudocysts (18/20, 90%). Postcontrast T1-weighted MRI revealed no significant enhancement (3/5, 60%) and mild enhancement (2/5, 40%). The incidence of cerebral cryptococcal granuloma were 35% (7/20). Nineteen of 26 patients with lesions outside the basal ganglia, of which 13 patients also complicated with basal ganglia lesions. Postcontrast T1-weighted MRI revealed no significant enhancement. The incidence of cryptococcal granuloma and meningeal thickening were 15.7% (3/19) and 26.3% (5/19), respectively. Postcontrast T1-weighted MRI meningeal thickening revealed enhancement (5/5, 100%).
 Conclusion: The incidence of brain MRI abnormality in AIDS complicated with central nervous system Cryptococcus infection may not be low, and the lesions are mostly located in the basal ganglia. It most frequently displays the dilated VRS/gelatinous spseudocysts. It can also be showed cryptococcal granuloma. Postcontrast T1-weighted MRI often reveals no enhancement or mild enhancement.

Large-scale gene co-expression network as a source of functional annotation for cattle genes.

BACKGROUND: Genome sequencing and subsequent gene annotation of genomes has led to the elucidation of many genes, but in vertebrates the actual number of protein coding genes are very consistent across species (~20,000). Seven years after sequencing the cattle genome, there are still genes that have limited annotation and the function of many genes are still not understood, or partly understood at best. Based on the assumption that genes with similar patterns of expression across a vast array of tissues and experimental conditions are likely to encode proteins with related functions or participate within a given pathway, we constructed a genome-wide Cattle Gene Co-expression Network (CGCN) using 72 microarray datasets that contained a total of 1470 Affymetrix Genechip Bovine Genome Arrays that were retrieved from either NCBI GEO or EBI ArrayExpress. RESULTS: The total of 16,607 probe sets, which represented 11,397 genes, with unique Entrez ID were consolidated into 32 co-expression modules that contained between 29 and 2569 probe sets. All of the identified modules showed strong functional enrichment for gene ontology (GO) terms and Reactome pathways. For example, modules with important biological functions such as response to virus, response to bacteria, energy metabolism, cell signaling and cell cycle have been identified. Moreover, gene co-expression networks using "guilt-by-association" principle have been used to predict the potential function of 132 genes with no functional annotation. Four unknown Hub genes were identified in modules highly enriched for GO terms related to leukocyte activation (LOC509513), RNA processing (LOC100848208), nucleic acid metabolic process (LOC100850151) and organic-acid metabolic process (MGC137211). Such highly connected genes should be investigated more closely as they likely to have key regulatory roles. CONCLUSIONS: We have demonstrated that the CGCN and its corresponding regulons provides rich information for experimental biologists to design experiments, interpret experimental results, and develop novel hypothesis on gene function in this poorly annotated genome. The network is publicly accessible at http://www.animalgenome.org/cgi-bin/host/reecylab/d .

Animal QTLdb: an improved database tool for livestock animal QTL/association data dissemination in the post-genome era.

The Animal QTL database (QTLdb; http://www.animalgenome.org/QTLdb) is designed to house all publicly available QTL and single-nucleotide polymorphism/gene association data on livestock animal species. An earlier version was published in the Nucleic Acids Research Database issue in 2007. Since then, we have continued our efforts to develop new and improved database tools to allow more data types, parameters and functions. Our efforts have transformed the Animal QTLdb into a tool that actively serves the research community as a quality data repository and more importantly, a provider of easily accessible tools and functions to disseminate QTL and gene association information. The QTLdb has been heavily used by the livestock genomics community since its first public release in 2004. To date, there are 5920 cattle, 3442 chicken, 7451 pigs, 753 sheep and 88 rainbow trout data points in the database, and at least 290 publications that cite use of the database. The rapid advancement in genomic studies of cattle, chicken, pigs, sheep and other livestock animals has presented us with challenges, as well as opportunities for the QTLdb to meet the evolving needs of the research community. Here, we report our progress over the recent years and highlight new functions and services available to the general public.

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens.

The rise of antimicrobial resistance in ESKAPEE pathogens poses significant clinical challenges, especially in polymicrobial infections. Bacteriophage-derived endolysins offer promise in combating this crisis, but face practical hurdles. Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. We assessed the resulting chimeric proteins' bactericidal activity against ESKAPEE pathogens in vitro. ApoE23-Kp84B (CHU-1) reduced over 3 log units of CFU for A. baumannii, E. faecalis, K. pneumoniae within 1 h, while COG133-Kp84B (CHU-2) showed significant efficacy against S. aureus. COG133-L1-Kp84B, with a GS linker insertion in CHU-2, exhibited outstanding bactericidal activity against E. cloacae and P. aeruginosa. Scanning electron microscopy revealed alterations in bacterial morphology after treatment with engineered endolysins. Notably, CHU-1 demonstrated promising anti-biofilm and anti-persister cell activity against A. baumannii and E. faecalis but had limited efficacy in a bacteremia mouse model of their coinfection. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively.

Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology.

BACKGROUND: The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. RESULTS: A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network. CONCLUSIONS: These validated results show significant improvement over current bovine genome annotations.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.