Role of mitochondria in renal ischemia-reperfusion injury.

Acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (IRI) has a high morbidity and mortality, representing a worldwide problem. The kidney is an essential organ of metabolism that has high blood perfusion and is the second most mitochondria-rich organ after the heart because of the high ATP demands of its essential functions of nutrient reabsorption, acid-base and electrolyte balance, and hemodynamics. Thus, these energy-intensive cells are particularly vulnerable to mitochondrial dysfunction. As the bulk of glomerular ultrafiltrate reabsorption by proximal tubules occurs via active transport, the mitochondria of proximal tubules must be equipped for detecting and responding to fluctuations in energy availability to guarantee efficient basal metabolism. Any insults to mitochondrial quality control mechanisms may lead to biological disruption, blocking the clearance of damaged mitochondria and resulting in morphological change and tissue dysfunction. Extensive research has shown that mitochondria have pivotal roles in acute kidney disease, so in this article, we discuss the role of mitochondria, their dynamics and mitophagy in renal ischemia-reperfusion injury.

[Effectiveness analysis of revision surgery after total hip arthroplasty assisted by artificial intelligence preoperative planning system].

Objective: To explore the short-term effectiveness of hip revision surgery guided by artificial intelligence preoperative planning (AIHIP) system. Methods: The clinical data of 22 patients (23 hips) who were admitted between June 2019 and March 2023 and met the selection criteria were retrospectively analyzed. There were 12 males and 10 females with an average age of 69.7 years (range, 44-90 years). There were 19 hips in the first revision, 3 hips in the second revision, and 1 hip in the third revision. The causes of revision included 12 hips with prosthesis loosening, 4 hips with acetabular cup loosening, 3 hips with osteolysis, 2 hips with acetabular dislocation, 1 hip with postoperative infection, and 1 hip with prosthesis wear. There were 6 hips in stage ⅡA, 9 hips in stage ⅡB, 4 hips in stage ⅡC, 3 hips in stage ⅢA, and 1 hip in stage ⅢB according to Paprosky staging of acetabular bone defect. The replacement of prosthesis type, operation time, hospitalization stay, ground active condition, and postoperative infection, fracture, prosthesis loosening, and other adverse events were recorded. The function of the affected limb was evaluated by Harris score before operation, at 1 week and 6 months after operation, and the range of motion of the hip joint was compared before operation and at 6 months after operation. Results: The operation time was 85-510 minutes, with an average of 241.8 minutes; the hospitalization stay was 7-35 days, with an average of 15.2 days; the time of disassociation from the walker was 2-108 days, with an average of 42.2 days. All the 22 patients were followed up 8-53 months (mean, 21.7 months). No adverse events such as prosthesis loosening or infection occurred in the rest of the patients, except for postoperative hematoma of the thigh in 1 patient and dislocation of the hip in 1 hip. The matching degree of acetabular cup was completely matched in 22 hips and mismatched in 1 hip (+2), the matching rate was 95.65%. The matching degree of femoral stem was completely matched in 22 hips and generally matched in 1 hip (-1), and the matching rate was 100%. The Harris scores were 55.3±9.8 and 89.6±7.2 at 1 week and 6 months after operation, respectively, which significantly improved when compared with before operation (33.0±8.6, P<0.05), and further improved at 6 months after operation than at 1 week after operation ( P<0.05). The function of hip joint was evaluated by Harris score at 6 months after operation, and 21 hips were good and 2 hips were moderate, which could meet the needs of daily life. The range of motion of hip joint was (111.09±10.11)° at 6 months after operation, which was significantly different from (79.13±18.50)° before operation ( t=-7.269, P<0.001). Conclusion: AIHIP system can improve the accuracy of revision surgery, reduce the difficulty of surgery, and achieve good postoperative recovery and satisfactory short-term effectiveness.

How to report and make sense of a new HIV-1 circulating recombinant form?

Co-circulation of multiple HIV-1 subtypes in the same high-risk groups leads to the on-going generation of various inter-subtype recombinants, including unique (URFs) and circulating (CRFs) recombinant forms, which brings a new challenge for the prevention and eradication of HIV/AIDS. Identification and prompt reporting of new CRFs will provide not only new insights into the understanding of genetic diversity and evolution of HIV-1, but also an early warning of potential prevalence of these variants. Currently, 140 HIV-1 CRFs have been described; however, their prevalence and clinical importance are less concerned. Apart from the mosaic genomic maps, less other valuable information, including the clinical and demographic data, genomic sequence characteristics, origin and evolutionary dynamics, as well as representative genomic fragments for determining the variants, are available for most of these CRFs. Accompanied with the growing increase of HIV-1 full-length genomic sequences, more and more CRFs will be identified in the near future due to the high recombination potential of HIV-1. Here, we discuss the prevalence and clinical importance of various HIV-1 CRFs and propose how to report and make sense of a new HIV-1 CRF.

The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

A novel extraction-free dual HiFi-LAMP assay for detection of methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a leading cause of bacteremia and blood stream infections. Methicillin-resistant S. aureus (MRSA) that first appeared in 1961 often caused hospital-acquired infections (HAIs) and community-acquired infections (CAIs) and was associated with high mortality rate. Accurate and rapid point-of-care testing (POCT) of MRSA is crucial for clinical management and treatment of MRSA infections, as well as the prevention and control of HAIs and CAIs. Here, we reported a novel extraction-free dual HiFi-LAMP assay for discriminative detection of methicillin-susceptible S. aureus and MRSA. The dual HiFi-LAMP assay can detect 30 copies/reaction of nuc and mecA genes with detection limits of 147 and 158 copies per 25 µL reaction, respectively. A retrospective clinical evaluation with 107 clinical S. aureus isolates showed both sensitivity and specificity of 100%. A prospective clinical evaluation with 35 clinical samples revealed a specificity of 100% and a sensitivity of 92.3%. The dual HiFi-LAMP assay can detect almost all S. aureus samples (141/142; 99.3%) within 20 min, implying that the entire HiFi-LAMP assay (including sample process) can be completed within 40 min, extremely significantly shorter than 3-5 days by the traditional clinical microbial culture and antibiotic susceptibility testing. The novel extraction-free dual HiFi-LAMP assay can be used as a robust POCT tool to promote precise diagnosis and treatment of MRSA infections in hospitals and to facilitate surveillance of MRSA at hospital and community settings.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) was associated with high mortality rate and listed as a "priority pathogen" by the World Health Organization. Accurate and rapid point-of-care testing (POCT) of MRSA is critically required for clinical management and treatment of MRSA infections. Some previous LAMP-based POCT assays for MRSA might be questionable due to their low specificity and the lack of appropriate evaluation directly using clinical samples. Furthermore, they are relatively tedious and time-consuming because they require DNA extraction and lack multiplex detection capacity. Here, we reported a novel extraction-free dual HiFi-LAMP assay for discriminative detection of MRSA and methicillin-susceptible S. aureus. The assay has high specificity and sensitivity and can be completed within 40 min. Clinical evaluation with real clinical samples and clinical isolates showed excellent performance with 100% specificity and 92.3%-100% sensitivity. The novel extraction-free assay may be a robust POCT tool to promote precise diagnosis of MRSA infections and facilitate surveillance of MRSA at hospital and community settings.

Rapid detection of four major HFMD-associated enteroviruses by multiplex HiFi-LAMP assays.

Hand, foot, and mouth disease (HFMD) caused by various enteroviruses is a major public health concern globally. Human enterovirus 71(EVA71), coxsackievirus A16 (CVA16), coxsackievirus A6 (CVA6), and coxsackievirus A10 (CVA10) are four major enteroviruses responsible for HFMD. Rapid, accurate, and specific point-of-care (POC) detection of the four enteroviruses is crucial for the prevention and control of HFMD. Here, we developed two multiplex high-fidelity DNA polymerase loop-mediated isothermal amplification (mHiFi-LAMP) assays for simultaneous detection of EVA71, CVA16, CVA6, and CVA10. The assays have good specificity and exhibit high sensitivity, with limits of detection (LOD) of 11.2, 49.6, 11.4, and 20.5 copies per 25 µL reaction for EVA71, CVA16, CVA6, and CVA10, respectively. The mHiFi-LAMP assays showed an excellent clinical performance (sensitivity 100.0%, specificity 83.3%, n = 47) when compared with four singleplex RT-qPCR assays (sensitivity 93.1%, specificity 100%). In particular, the HiFi-LAMP assays exhibited better performance (sensitivity 100.0%, specificity 100%) for CVA16 and CVA6 than the RT-qPCR assays (sensitivity 75.0-92.3%, specificity 100%). Furthermore, the mHiFi-LAMP assays detected all clinical samples positive for the four enteroviruses within 30 min, obviously shorter than about 1-1.5 h by the RT-qPCR assays. The new mHiFi-LAMP assays can be used as a robust point-of-care testing (POCT) tool to facilitate surveillance of HFMD at rural and remote communities and resource-limited settings.

The emerging role of ectodermal neural cortex 1 in cancer.

Ectodermal neural cortex 1 (ENC1) is a protein that plays a crucial role in the regulation of various cellular processes such as cell proliferation, differentiation, and apoptosis. Numerous studies have shown that ENC1 is overexpressed in various types of cancers, including breast, lung, pancreatic, and colorectal cancer, and its upregulation is correlated with a poorer prognosis. In addition to its role in cancer growth and spreading, ENC1 has also been linked to neuronal process development and neural crest cell differentiation. In this review, we provide an overview of the current knowledge on the relationship between ENC1 and cancer. We discuss the molecular mechanisms by which ENC1 contributes to tumorigenesis, including its involvement in multiple oncogenic signaling pathways. We also summarize the potential of targeting ENC1 for cancer therapy, as its inhibition has been shown to significantly reduce cancer cell invasion, growth, and metastasis. Finally, we highlight the remaining gaps in our understanding of ENC1's role in cancer and propose potential directions for future research.

Patterned growth of two-dimensional atomic layer semiconductors.

Transition metal dichalcogenides (TMDCs), which are representative of two-dimensional (2D) semiconductors, have attracted tremendous attention over the last two decades. TMDCs are regarded as potential candidates in modern nano- and optoelectronic applications due to their unique crystal structures and outstanding electronic and optoelectronic properties. For practical use, 2D semiconductors need to be fabricated with diverse morphologies for integration into electronic devices and to perform different functionalities. Controlled patterning synthesis with programmable geometries is therefore highly desired. We review state-of-the-art strategies for the patterned growth of atomic layer TMDCs and their heterostructures, including additive manufacturing and subtractive manufacturing for patterning single TMDC materials and the introduction of other low-dimensional nanomaterials as growth templates or hetero-atoms for element conversion in patterning TMDC heterostructures. The optoelectronic and electronic applications of the as-grown monolayer TMDC patterns are introduced. Future challenges and the prospects for the patterned growth of 2D semiconductors are discussed based on present achievements.

Genomic Characteristics of the New HIV-1 CRF07_BC K28E32 Variant.

Accompanied with the appearance and prevalence of the new K28E32 variant among men who have sex with men, HIV-1 circulating recombinant form 07_BC (CRF07_BC) was becoming the most predominant subtype circulating in China. The K28E32 variant with five specific mutations in reverse transcriptase coding region appears to have significantly higher in vitro HIV-1 replication ability than the wild-type strain. In this study, we characterized the special mutations/substitutions in the K28E32 variant at the genomic level. Ten specific mutations that rarely appeared in other six main HIV-1 subtypes/CRFs (A-D, CRF01_AE, and CRF02_AG) were identified in the coding genes/regions of the K28E32 variant, including S77L and a novel seven-amino acid detection (32DKELYPL38) (p6Δ7) in p6, I135L in integrase, T189S in Vif, H/Y15L/F in Vpr, I264V/A and LV/LI328-329VG in gp41, and H82C and S97P in Rev. The special locations of the novel p6Δ7, and gp41 mutations I264V/A and LV/LI328-329VG in crucial protein functional domains suggest that these mutations might be functionally important to the K28E32 variant. Furthermore, eight specific substitutions were identified in Rev responsive element (RRE) of the K28E32 variant, and were revealed to increase the stability of RRE structure with a lower minimum free energy. Whether these mutations/substitutions contribute to improved transmissibility of the CRF07_BC K28E32 variant needs to be further confirmed.

Surfactant-Aided Stabilization of Individual Carbon Nanotubes in Water around the Critical Micelle Concentration.

Surfactants are widely used to disperse single-walled carbon nanotubes (SWCNTs) and other nanomaterials for liquid-phase processing and characterization. Traditional techniques, however, demand high surfactant concentrations, often in the range of 1-2 wt/v% of the solution. Here, we show that optimal dispersion efficiency can be attained at substantially lower surfactant concentrations of approximately 0.08 wt/v%, near the critical micelle concentration. This unexpected observation is achieved by introducing "bare" nanotubes into water containing the anionic surfactant sodium deoxycholate (DOC) through a superacid-surfactant exchange process that eliminates the need for ultrasonication. Among the diverse ionic surfactants and charged biopolymers explored, DOC exhibits the highest dispersion efficiency, outperforming sodium cholate, a structurally similar bile salt surfactant containing just one additional oxygen atom compared to DOC. Employing all-atomistic molecular dynamics simulations, we unravel that the greater stabilization by DOC arises from its higher binding affinity to nanotubes and a substantially larger free energy barrier that resists nanotube rebundling. Further, we find that this barrier is nonelectrostatic in nature and does not obey the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal stability, underscoring the important role of nonelectrostatic dispersion and hydration interactions at the nanoscale, even in the case of ionic surfactants like DOC. These molecular insights advance our understanding of surfactant chemistry at the bare nanotube limit and suggest low-energy, surfactant-efficient solution processing of SWCNTs and potentially other nanomaterials.

The microbiome, resistome, and their co-evolution in sewage at a hospital for infectious diseases in Shanghai, China.

The emergence of antibiotic-resistant bacteria (ARB) caused by the overuse of antibiotics severely threatens human health. Hospital sewage may be a key transmission hub for ARB. However, the complex link between the microbiome and resistomeresistance in hospital sewage remains unclear. In this study, metagenomic assembly and binning methods were used to investigate the microbial community, resistome, and association of antibiotic resistance genes (ARGs) with ARB in sewage from 10 representative sites (outpatient building, surgery building, internal medicine buildings [IMB1-4], staff dormitory, laboratory animal building, tuberculosis building [TBB], and hospital wastewater treatment plant) of a hospital in Shanghai from June 2021 to February 2022. A total of 252 ARG subtypes, belonging to 17 antibiotic classes, were identified. The relative abundance of KPC-2 was higher at IMBs and TBB than at other sites. Of the ARG-carrying contigs, 47.3%-62.6% were associated with mobile genetic elements, and the proportion of plasmid-associated ARGs was significantly higher than that of chromosome-associated ARGs. Although a similar microbiome composition was shared, certain bacteria were enriched at different sites. Potential pathogens Enterococcus B faecium and Klebsiella pneumoniae were primarily enriched in IMB2 and IMB4, respectively. The same ARGs were identified in diverse bacterial hosts (especially pathogenic bacteria), and accordingly, the latter possessed multiple ARGs. Furthermore, gene flow was frequently observed in the sewage of different buildings. The results provide crucial information on the characterization profiles of resistomes in hospital sewage in Shanghai.IMPORTANCEEnvironmental antibiotic resistance genes (ARGs) play a critical role in the emergence and spread of antimicrobial resistance, which poses a global health threat. Wastewater from healthcare facilities serves as a significant reservoir for ARGs. Here, we characterized the microbial community along with the resistome (comprising all antibiotic resistance genes) in wastewater from a specialized hospital for infectious diseases in Shanghai. Potential pathogenic bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus B faecium) were frequently detected in hospital wastewater and carried multiple ARGs. A complex link between microbiome and resistome was observed in the wastewater of this hospital. The monitoring of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater might be of great significance for preventing the spread of ARB.

Identification of differentially expressed circRNAs in prostate cancer of different clinical stages by RNA sequencing.

Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA-miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.

Metal Selenide-Based Superstructure Nanoarrays with Ultrahigh Capacity for Alkaline Zn Batteries.

Transition metal selenides (TMSs) have great potential as cathode materials for alkaline Zn batteries (AZBs) owing to their high theoretical capacity and metallic conductivity. However, achieving a high specific capacity remains a formidable challenge due to the low structural stability and sluggish reaction kinetics of single-phase TMS. Herein, a facile method for fabricating a robust CoSe2 @Ni3 Se4 @Ni(OH)2 superstructure nanoarray (CNSNA) as an AZB cathode is presented. The sophisticated design enables structural stability and abundant active surface sites for efficient charge storage. Furthermore, the redox mediator K3 [Fe(CN)6 ] is employed to expedite the reaction kinetics and introduce supplementary redox reactions, further enhancing the charge storage capability. Consequently, the CNSNA electrode delivers an exceptional specific capacitance (609.08 mAh g-1 at 1 A g-1 ), surpassing all previously reported selenide-based materials. High-rate capability (239.37 mAh g-1 at 20 A g-1 ) and long cycling stability have also been achieved. The comprehensive charge storage mechanism studies confirmed the structural integrity, kinetic improvement, and high reactivity of the CNSNA superstructure. Moreover, the corresponding AZB based on CNSNA demonstrates an extraordinarily high energy density of 516.58 Wh kg-1 . The work offers guidance in the construction of superstructure-based TMS electrode materials, paving the way for the development of high-performance AZBs.

Rapid detection of human influenza A viruses by HFman probe-based loop-mediated isothermal amplification assays.

Since China abandoned the zero-COVID policy at the end of 2022, a wave of severe Flu pandemic emerged in China. Rapid and accurate diagnosis of Influenza A virus (IAV) is critical for clinical management and therapeutic decision-making of patients with fever. Here, we reported a novel IAV HF-LAMP assay, which can be performed with purified RNA or directly using clinical samples. The assays with purified RNA and clinical samples have high sensitivity with limit of detection (LOD) of 9.6 copies/reaction, 9900 copies/mL, and short sample-to-answer times of 36 and 50 min, respectively. Both assays showed high specificity and significantly higher IAV detection rate than the rapid antigen detection (RAD) assays. Furthermore, we found the vast majority (91.2 %) of children with fever during the pandemic were infected by IAV, and current IAV infection has a very narrow detectable window. The novel IVA HF-LAMP assays will provide robust tools to facilitate early diagnosis of IAV infection in current and future seasonal influenza epidemics.

Longitudinal anellome dynamics in the upper respiratory tract of children with acute respiratory tract infections.

Anelloviruses (AVs) are ubiquitous in humans and are the most abundant components of the commensal virome. Previous studies on the diversity, transmission, and persistence of AVs mainly focused on the blood or transplanted tissues from adults; however, the profile of the anellome in the respiratory tract in children are barely known. We investigated the anellome profile and their dynamics in the upper respiratory tract from a cohort of children with acute respiratory tract infections (ARTIs). Different to that in adult, betatorquevirus is the most abundant genus, followed by alphatorquevirus. We found that the relative abundance of betatorquevirus was higher in earlier time points, and in contrast, the abundance of alphatorquevirus was higher in later time points; these results might suggest that betatorquevirus decreased with age and alphatorquevirus increased with age in childhood. No difference regarding the diversity and abundance of anellome was found between single and multiple ARTIs, consistent with the idea that AV is not associated with certain disease. Most AVs are transient, and a small proportion (8 per cent) of them were found to be possibly persistent, with persistence time ranging from 1 month to as long as 56 months. Furthermore, the individual respiratory anellome appeared to be unique and dynamic, and the replacement of existing AVs with new ones are common over different time points. These findings demonstrate that betatorquevirus may be the early colonizer in children, and the individual respiratory anellome is unique, which are featured by both chronic infections and AV community replacement.

Inverse CO2/C2H2 separation assisted by coordinated water in a dysprosium(III) metal-organic framework.

An ultramicroporous metal-organic framework (MOF) constructed from dysprosium(III) and oxalate, termed Dy-F-oxa, is carefully studied for inverse separation of CO2 from C2H2. Adsorption experiments and modeling studies reveal that the high CO2 adsorption is attributed to the preferential sites for CO2 by coordinated water. After the equimolar gas mixture breakthrough experiment, C2H2 can be directly produced as a pure effluent.

Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration.

Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT's predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.

Evolution of the Probe-Based Loop-Mediated Isothermal Amplification (LAMP) Assays in Pathogen Detection.

Loop-mediated isothermal amplification (LAMP), as the rank one alternative to a polymerase chain reaction (PCR), has been widely applied in point-of-care testing (POCT) due to its rapid, simple, and cost-effective characteristics. However, it is difficult to achieve real-time monitoring and multiplex detection with the traditional LAMP method. In addition, these approaches that use turbidimetry, sequence-independent intercalating dyes, or pH-sensitive indicators to indirectly reflect amplification can result in false-positive results if non-specific amplification occurs. To fulfill the needs of specific target detection and one-pot multiplex detection, a variety of probe-based LAMP assays have been developed. This review focuses on the principles of these assays, summarizes their applications in pathogen detection, and discusses their features and advantages over the traditional LAMP methods.

A Diverse Virome Is Identified in Parasitic Flatworms of Domestic Animals in Xinjiang, China.

Parasitic flatworms infect diverse vertebrates and are major threats to animal and even human health; however, little is known about the virome of these lower life forms. Using viral metagenomic sequencing, we characterized the virome of the parasitic flatworms collected from major domestic animals, including Dicrocoelium lanceatum and Taenia hydatigena, Echinococcus granulosus sensu stricto and Echinococcus multilocularis. Seven and three different viruses were discovered from D. lanceatum and T. hydatigena, respectively, and no viral sequences were found in adult tapeworms and protoscoleces of E. granulosus sensu stricto and E. multilocularis. Two out of the five parasitic flatworm species carry viruses, showing a host specificity of these viruses. These viruses belong to the Parvoviridae, Circoviridae, unclassified circular, Rep-encoding single-stranded (CRESS) DNA virus, Rhabdoviridae, Endornaviridae, and unclassified RNA viruses. The presence of multiple highly divergent RNA viruses, especially those that cluster with viruses found in marine animals, implies a deep evolutionary history of parasite-associated viruses. In addition, we found viruses with high identity to common pathogens in dogs, including canine circovirus and canine parvovirus 2. The presence of these viruses in the parasites implies that they may infect parasitic flatworms but does not completely exclude the possibility of contamination from host intestinal contents. Furthermore, we demonstrated that certain viruses, such as CRESS DNA virus may integrate into the genome of their host. Our results expand the knowledge of viral diversity in parasites of important domestic animals, highlighting the need for further investigations of their prevalence among other parasites of key animals. IMPORTANCE Characterizing the virome of parasites is important for unveiling the viral diversity, evolution, and ecology and will help to understand the "Russian doll" pattern among viruses, parasites, and host animals. Our data indicate that diverse viruses are present in specific parasitic flatworms, including viruses that may have an ancient evolutionary history and viruses currently circulating in parasite-infected host animals. These data also raise the question of whether parasitic flatworms acquire and/or carry some viruses that may have transmission potential to animals. In addition, through the study of virus-parasite-host interactions, including the influence of viral infection on the life cycle of the parasite, as well as its fitness and pathogenicity to the host, we could find new strategies to prevent and control parasitic diseases.

Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status.

Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.