Clinical features, treatment and prognosis of patients with endogenous infectious endophthalmitis.

PURPOSE: To investigate whether the clinical characteristics, treatment and prognosis of endogenous infectious endophthalmitis (EIE) have changed over the past 5 years. METHODS: Retrospectively analyze all articles about EIE published in the PubMed, Web of Science, and Embase databases from 2017 to 2021. RESULTS: A total of 128 patients and 147 eyes (46 left and 60 right) were included in the study. The mean age at diagnosis was 51 ± 19 years. The most common risk factors were diabetes and intravenous drug use. From 2017 to 2021, Klebsiella was the most common pathogenic microorganism (22%), and vitreous culture had the highest positivity rate. The most common complaint was blurred vision. The mean visual acuity (logMAR) at onset was 2.84, and the clinical symptoms were vitreal inflammation and opacity (63%), ocular pain (37%), and conjunctival congestion (36%). The ocular inflammation could be reduced by intraocular antibiotics or vitrectomy. However, the visual prognosis, with a mean logMAR of 2.73; only 50% of the eyes reached a visual acuity level of finger count and above. Changes in diagnostics over the past 5 years have mainly manifested as more diverse microorganism culture methods. In addition to conventional culture methods, PCR, sputum culture and aqueous humour culture are also commonly used for the diagnosis of pathogenic bacteria, improving the positive culture rate and visual prognosis. CONCLUSION: The prognosis of EIE is poor. It is recommended to pay attention to the pathogenic bacteria culture results and accompanying systemic diseases and to diagnose and treat patients as soon as possible.

[Intraperitoneal injection of human-derived anti-c-Met single-chain antibody inhibits the growth of transplanted tumours in A549 lung adenocarcinoma-loaded mice].

Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice. Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells. Once the tumors were formed, IRDye680 LT N-hydroxysuccinimide (NHS) ester-labeled Met scFv was administered intraperitoneally. Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice. The affinity between c-Met and the antibody in tumor cells was detected. Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv. Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues. Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours. After approximately 48 hours, fluorescent signals began to accumulate in the tumor tissue. Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues; regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice. Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.

Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the gastrointestinal tract, including two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Metabolic disorders are important factors in the development of IBD. However, the evidence for the causal relationship between blood metabolites and IBD remains limited. A two-sample MR analysis was applied to evaluate relationships between 486 blood metabolites and IBD. The inverse variance weighted method was chosen as the primary MR analysis method. False discovery rate correction was used to control for false positives in multiple testing. Following complementary and sensitivity analyses were conducted using methods such as weight median, MR-egger, weighted mode, simple mode, Cochran Q test, and MR-PRESSO. Moreover, we performed replication, meta-analysis, Steiger test, and linkage disequilibrium score regression to enhance the robustness of the results. Additionally, we performed metabolic pathway analysis to identify potential metabolic pathways. As a result, we identified four significant causal associations between four blood metabolites and two IBD subtypes. Specifically, one metabolite was identified as being associated with the development of CD (mannose: odds ratio (OR) = 0.19, 95% confidence interval (CI) 0.08-0.43, P = 8.54 × 10-5). Three metabolites were identified as being associated with the development of UC (arachidonate (20:4n6): OR = 0.18, 95% CI 0.11-0.30, P = 2.09 × 10-11; 1, 5-anhydroglucitol: OR = 2.21, 95% CI 1.47-3.34, P = 1.50 × 10-4; 2-stearoylglycerophosphocholine: OR = 2.66, 95% CI 1.53-4.63, P = 5.30 × 10-4). The findings of our study suggested that the identified metabolites and metabolic pathways can be considered as useful circulating metabolic biomarkers for the screening and prevention of IBD in clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.

[Relationship between GTSE1 and Cell Cycle and Potential Regulatory Mechanisms 
in Lung Cancer Cells].

The regulation of the cell cycle is essential for maintaining normal cellular function, especially in the development of diseases such as lung cancer. The cell cycle consists of four major phases (G1, S, G2 and M phases), which are characterized by a series of precise molecular events to ensure proper cell proliferation and division. In lung cancer cells, cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells. G2 and S-phase expressed 1 (GTSE1) is a regulatory protein found in the cytoplasm of the cell, which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis. GTSE1 affects cell cycle progression by interacting with cyclin-dependent kinase inhibitor 1A (p21) and maintaining the stability of p21, which in turn inhibits the activity of cyclin-dependent kinase 1/2 (CDK1/2). In addition, GTSE1 is also involved in the regulation of tumor protein 53 (p53) signaling pathway. With the assistance of mouse double minute 2 homolog (MDM2), GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation, thus affecting cell cycle and cell death-related signaling pathways. This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer, as well as its potential mechanisms involved in cell cycle regulation.
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Deciphering fatty acid biosynthesis-driven molecular subtypes in pancreatic ductal adenocarcinoma with prognostic insights.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to its high heterogeneity and aggressiveness. Recognizing the urgency to delineate molecular subtypes, our study focused on the emerging field of lipid metabolism remodeling in PDAC, particularly exploring the prognostic potential and molecular classification associated with fatty acid biosynthesis. METHODS: Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were performed to evaluate the dysregulation of lipid metabolism in PDAC. Univariate cox analysis and the LASSO module were used to build a prognostic risk score signature. The distinction of gene expression in different risk groups was explored by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The biological function of Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5), a pivotal gene within 7-hub gene signature panel, was validated through in vitro assays. RESULTS: Our study identified a 7-hub gene signature associated with fatty acid biosynthesis-related genes (FRGs), providing a robust tool for prognosis prediction. The high-FRGs score group displayed a poorer prognosis, decreased immune cell infiltration, and a higher tumor mutation burden. Interestingly, this group exhibited enhanced responsiveness to various compounds according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. Notably, ACSL5 was upregulated in PDAC and essential for tumor progression. CONCLUSION: In conclusion, our research defined two novel fatty acid biosynthesis-based subtypes in PDAC, characterized by distinct transcriptional profiles. These subtypes not only served as prognostic indicator, but also offered valuable insights into their metastatic propensity and therapeutic potential.

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

A nanobody-mediated drug system against largemouth bass virus delivered by bacterial nanocellulose in Micropterus salmoides.

Diseases caused by pathogens severely hampered the development of aquaculture, especially largemouth bass virus (LMBV) has caused massive mortality and severe economic losses to the culture of largemouth bass (Micropterus salmoides). Considering the environmental hazards and human health, effective and environmentally friendly therapy strategy against LMBV is of vital importance and in pressing need. In the present study, a novel nanobody (NbE4) specific for LMBV was selected from a phage display nanobody library. Immunofluorescence and indirect ELISA showed that NbE4 could recognize LMBV virions and had strong binding capacity, but RT-qPCR evidenced that NBE4 did not render the virus uninfectious. Besides, antiviral drug ribavirin was used to construct a targeted drug system delivered by bacterial nanocellulose (BNC). RT-qPCR revealed that NbE4 could significantly enhance the antiviral activity of ribavirin in vitro and in vivo. The targeted drug delivery system (BNC-Ribavirin-NbE4, BRN) reduced the inflammatory response caused by LMBV infection and improved survival rate (BRN-L, 33.3 %; BRN-M, 46.7 %; BRN-H, 56.7 %)compared with control group (13.3 %), ribavirin group (RBV, 26.7 %) and BNC-ribavirin (BNC-R, 40.0 %), respectively. This research provided an effective antiviral strategy that improved the drug therapeutic effect and thus reduced the dosage.

Hybridizing carbonate and ether at molecular scales for high-energy and high-safety lithium metal batteries.

Commonly-used ether and carbonate electrolytes show distinct advantages in active lithium-metal anode and high-voltage cathode, respectively. While these complementary characteristics hold promise for energy-dense lithium metal batteries, such synergy cannot be realized solely through physical blending. Herein, a linear functionalized solvent, bis(2-methoxyethyl) carbonate (BMC), is conceived by intramolecularly hybridizing ethers and carbonates. The integration of the electron-donating ether group with the electron-withdrawing carbonate group can rationalizes the charge distribution, imparting BMC with notable oxidative/reductive stability and relatively weak solvation ability. Furthermore, BMC also offers advantages including the ability to slightly dissolve LiNO3, excellent thermostability and nonflammability. Consequently, the optimized BMC-based electrolyte, even with typical concentrations in the single solvent, demonstrates high-voltage tolerance (4.4 V) and impressive Li plating/stripping Coulombic efficiency (99.4%). Moreover, it fulfills practical lithium metal batteries with satisfactory cycling performance and exceptional tolerance towards thermal/mechanical abuse, showcasing its suitability for safe high-energy lithium metal batteries.

Exploiting Molecular Orders at the Interface of Microdroplets for Intelligent Materials.

ConspectusThe intrinsic molecular order of liquid crystals (LCs) and liquid crystalline elastomers (LCEs) is the origin of their stimuli-responsive properties. The programmable responsiveness and functionality, such as shape morphing and color change under external stimuli, are the key features that attract interest in designing LC- and LCE-based intelligent material platforms. Methods such as mechanical stretching and shearing, surface alignment, and field-assisted alignment have been exploited to program the order of LC molecules for the desired responsiveness. However, the huge size mismatch between the nanometer-sized LC mesogens and the targeted macroscopic objects calls for questions about how to delicately control molecular order for desired performance. Microparticles that can be synthesized with intrinsic molecular order precisely controlled to micrometer size can be used as building blocks for bulk materials, thus offering opportunities to bridge the gap and transcend molecular orders across scales. By taking advantage of the interfacial anchoring effects, we can control and engineer the molecular orders inside the microdroplets, allowing for the realization of various responsive behaviors. Furthermore, designer LC microparticles with multiple responsiveness can be assembled and confined within a matrix, opening a new pathway to engineering LC-enabled intelligent materials.In this Account, we present our recent work on exploiting the molecular order inside microdroplets for the construction of intelligent materials. We briefly introduce the typical chemicals used in the synthesis and the methods developed to control LC molecular alignment within a microdroplets. We then present examples of microparticles synthesized from microdroplets that can transform into complex morphologies upon cooling from the isotropic to nematic phase or due to phase separation within the droplets coupled with the segregation of LC oligomers (LCOs) with polydisperse chain lengths. Furthermore, we show the synthesis of elliptical LCE microparticles and exploit their thermal and magnetic responsiveness to program shape-morphing behaviors and microarrays with switchable optical polarization. By mixing magnetic nanoparticles in cholesteric liquid crystals (CLCs) and silicone oils, we created Janus microparticles capable of color switching for camouflage and information encryption. Moreover, we can engineer complex molecular orders in LCE microparticles by mixing different surfactants, yielding microparticles of diverse anisotropic, temperature-responsive shapes after photopolymerization and extraction of the template LC molecules with different solvents. We conclude the Account with an outlook on the design of intelligent material systems via the design of unprecedented molecular ordering within the microparticles and their coupling with bulk materials.

A Ratiometric Biosensor Containing Manganese Dioxide Nanosheets and Nitrogen-Doped Quantum Dots for 2,4-Dichlorophenoxyacetic Acid Monitoring.

Nanomaterials are desirable for sensing applications. Therefore, MnO2 nanosheets and nitrogen-doped carbon dots (NCDs) were used to construct a ratiometric biosensor for quantification of 2,4-dichlorophenoxyacetic acid. The MnO2 nanosheets drove the oxidation of colorless o-phenylenediamine to OPDox, which exhibits fluorescence emission peaks at 556 nm. The fluorescence of OPDox was efficiently quenched and the NCDs were recovered as the ascorbic acid produced by the hydrolyzed alkaline phosphatase (ALP) substrate increased. Owing to the selective inhibition of ALP activity by 2,4-D and the inner filter effect, the fluorescence intensity of the NCDs at 430 nm was suppressed, whereas that at 556 nm was maintained. The fluorescence intensity ratio was used for quantitative detection. The linear equation was F = 0.138 + 3.863·C 2,4-D (correlation coefficient R2 = 0.9904), whereas the limits of detection (LOD) and quantification (LOQ) were 0.013 and 0.040 µg/mL. The method was successfully employed for the determination of 2,4-D in different vegetables with recoveries of 79%~105%. The fluorescent color change in the 2,4-D sensing system can also be captured by a smartphone to achieve colorimetric detection by homemade portable test kit.

Insights into biogeochemistry and hot spots distribution characteristics of redox-sensitive elements in the hyporheic zone: Transformation mechanisms and contributing factors.

Biogeochemical hot spots play a crucial role in the cycling and transport of redox-sensitive elements (RSEs) in the hyporheic zone (HZ). However, the transformation mechanisms of RSEs and patterns of RSEs hot spots in the HZ remain poorly understood. In this study, hydrochemistry and multi-isotope (N/C/S/O) datasets were collected to investigate the transformation mechanisms of RSEs, and explore the distribution characteristics of RSEs transformation hot spots. The results showed that spatial variability in key drivers was evident, while temporal change in RSEs concentration was not significant, except for dissolved organic carbon. Bacterial sulfate reduction (BSR) was the primary biogeochemical process for sulfate and occurred throughout the area. Ammonium enrichment was mainly caused by the mineralization of nitrogenous organic matter and anthropogenic inputs, with adsorption serving as the primary attenuation mechanism. Carbon dynamics were influenced by various biogeochemical processes, with dissolved organic carbon mainly derived from C3 plants and dissolved inorganic carbon from weathering of carbonate rocks and decomposition of organic matter. The peak contribution of dissolved organic carbon decomposition to the DIC pool was 46.44 %. The concentration thresholds for the ammonium enrichment and BSR hot spots were identified as 1.5 mg/L and 8.84 mg/L, respectively. The distribution pattern of RSEs hot spots was closely related to the hydrogeological conditions. Our findings reveal the complex evolution mechanisms and hot spots distribution characteristics of RSEs in the HZ, providing a basis for the safe utilization and protection of groundwater resources.

Ultrasensitive Ochratoxin A Detection in Cereal Products Using a Fluorescent Aptasensor Based on RecJf Exonuclease-Assisted Target Recycling.

Ochratoxin A (OTA) is a mycotoxin widely found in foodstuffs such as cereal grains. It greatly threatens human health owing to its strong toxicity and high stability. Aptasensors have emerged as promising tools for the analysis of small molecule contaminants. Nucleic-acid-based signal amplification enables detectable signals to be obtained from aptasensors. However, this strategy often requires the use of complex primers or multiple enzymes, entailing problems such as complex system instability. Herein, we propose a fluorescent aptasensor for the ultrasensitive detection of OTA in cereal products, with signal amplification through RecJf exonuclease-assisted target recycling. The aptamer/fluorescein-labeled complementary DNA (cDNA-FAM) duplex was effectively used as the target-recognition unit as well as the potential substrate for RecJf exonuclease cleavage. When the target invaded the aptamer-cDNA-FAM duplex to release cDNA-FAM, RecJf exonuclease could cleave the aptamer bonded with the target and release the target. Thus, the target-triggered cleavage cycling would continuously generate cDNA-FAM as a signaling group, specifically amplifying the response signal. The proposed exonuclease-assisted fluorescent aptasensor exhibited a good linear relationship with OTA concentration in the range from 1 pg/mL to 10 ng/mL with an ultralow limit of detection (6.2 ng/kg of cereal). The analytical method showed that recoveries of the cereal samples ranged from 83.7 to 109.3% with a repeatability relative standard deviation below 8%. Importantly, the proposed strategy is expected to become a common detection model because it can be adapted for other targets by replacing the aptamer. Thus, this model can guide the development of facile approaches for point-of-care testing applications.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Chromatin region binning of gene expression for improving embryo cell subtype identification.

Mammalian embryonic development is a complex process, characterized by intricate spatiotemporal dynamics and distinct chromatin preferences. However, the quick diversification in early embryogenesis leads to significant cellular diversity and the sparsity of scRNA-seq data, posing challenges in accurately determining cell fate decisions. In this study, we introduce a chromatin region binning method using scChrBin, designed to identify chromatin regions that elucidate the dynamics of embryonic development and lineage differentiation. This method transforms scRNA-seq data into a chromatin-based matrix, leveraging genomic annotations. Our results showed that the scChrBin method achieves high accuracy, with 98.0% and 89.2% on two single-cell embryonic datasets, demonstrating its effectiveness in analyzing complex developmental processes. We also systematically and comprehensively analysis of these key chromatin binning regions and their associated genes, focusing on their roles in lineage and stage development. The perspective of chromatin region binning method enables a comprehensive analysis of transcriptome data at the chromatin level, allowing us to unveil the dynamic expression of chromatin regions across temporal and spatial development. The tool is available as an application at https://github.com/liameihao/scChrBin.

Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis.

Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders.

Insights into enhanced oxidation of benzophenone-type UV filters (BPs) by ferrate(VI)/ferrihydrite: Increased conversion of Fe(VI) to Fe(V)/Fe(IV).

In this work, the oxidation performance of a new ferrate(VI)/ferrihydrite (Fe(VI)/Fh) system was systematically explored to degrade efficiently six kinds of benzophenone-type UV filters (BPs). Fe(VI)/Fh system not only had a superior degradation capacity towards different BPs, but also exhibited higher reactivity over a pH range of 6.0-9.0. The second-order kinetic model successfully described the process of BP-4 degradation by heterogeneous Fh catalyzed Fe(VI) system (R2 = 0.93), and the presence of Fh could increase the BP-4 degradation rate by Fe(VI) by an order of magnitude (198 M-1·s-1 v.s. 14.2 M-1·s-1). Remarkably, there are higher utilization efficiency and potential of Fe(VI) in Fe(VI)/Fh system than in Fe(VI) alone system. Moreover, characterization and recycling experiments demonstrated that Fh achieved certain long-term running performance, and the residual Fe content of solution after clarifying process meet World Health Organization (WHO) guidelines for drinking water. The contributions of reactive species could be ranked as Fe(V)/Fe(IV) > Fe(VI) > â€¢OH. Fe(IV)/Fe(V) were the dominant species for the enhanced removal in the Fe(VI)/Fh system, whose percentage contribution (72 %-36 %) were much higher than those in Fe(VI) alone system (5 %-17 %). However, the contribution of Fe(VI) in oxidizing BP-4 should not be underestimated (20 %-56 %). These findings reasonably exploit available Fh resources to reduce the relatively high cost of Fe(VI), which offers a proper strategies for efficient utilization of high-valent iron species and may be used as a highly-efficient and cost-effective BPs purification method.

Phenotypic characteristics and immune response of Procypris merus following challenge with aquatic isolate of Klebsiella pneumoniae.

Currently, aquaculture is a relatively mature industry; however, disease problems are continuously threatening the industry and hindering its development to a certain extent. Klebsiella pneumoniae is one of the zoonotic bacteria widely present in different hosts and has caused some degree of harm to the aquaculture industry, posing a potential threat to the water environment and indirectly also affecting human food safety issues. In this study, K. pneumoniae was isolated from the aquaculture environment, named as ELD, and subjected to pathogenic and immunological related studies. The results of the study showed that the strain carries at least four virulence-related genes, magA, wabG, ureA and uge, and has developed resistance to at least seven antibacterial drugs, such as amoxicillin, doxycycline, rifampicin, and so on. Moreover, the strain is highly pathogenic and is capable of causing systemic clinical foci in Procypris merus. In addition, after infection with K. pneumoniae, the expression of IL-1ß, IL-8, HSP70 and C2 was upregulated in P. merus as a whole, whereas the expression of TNF-α did not change significantly in any of the tissues, which might be a kind of immune response of P. merus against K. pneumoniae infection. This study provides an important theoretical basis for the in-depth exploration of the pathogenic mechanism of K. pneumoniae in fish and the immune response that occurs after the disease is contracted in fish, as well as theoretical support for the development of effective preventive and therapeutic strategies against K. pneumoniae-infected aquatic animals in the future.

A Comprehensive Comparison of Six Publicly Available Algorithms for Localization of QRS Complex on Electrocardiograph.

The QRS complex is the most prominent feature of the electrocardiogram (ECG) that is used as a marker to identify the cardiac cycles. Identification of QRS complex locations enables arrhythmia detection and heart rate variability estimation. Therefore, accurate and consistent localization of the QRS complex is an important component of automated ECG analysis which is necessary for the early detection of cardiovascular diseases. This study evaluates the performance of six popular publicly available QRS complex detection methods on a large dataset of over half a million ECGs in a diverse population of patients. We found that a deep-learning method that won first place in the 2019 Chinese physiological challenge (CPSC-1) outperforms the remaining five QRS complex detection methods with an F1 score of 98.8% and an absolute sdRR error of 5.5 ms. We also examined the stratified performance of the studied methods on various cardiac conditions. All six methods had a lower performance in the detection of QRS complexes in ECG signals of patients with pacemakers, complete atrioventricular block, or indeterminate cardiac axis. We also concluded that, in the presence of different cardiac conditions, CPSC-1 is more robust than Pan-Tompkins which is the most popular model for QRS complex detection. We expect that this study can potentially serve as a guide for researchers on the appropriate QRS detection method for their target applications.Clinical Relevance-This study highlights the overall performance of publicly available QRS detection algorithms in a large dataset of diverse patients. We showed that there are specific cardiac conditions that are associated with the poor performance of QRS detection algorithms and may adversely influence the performance of algorithms that rely on accurate and reliable QRS detection.

Biomarkers for Prostate Cancer: From Diagnosis to Treatment.

Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management.

N-doped molybdenum oxide quantum dots as fluorescent probes for the quantitative detection of copper ions in environmental samples.

A novel, sensitive, and selective fluorescence sensor based on N-doped Mo oxide quantum dots (N-MoOx QDs) was fabricated for the detection of Cu2+ ions in water. The presence of Cu2+ induced dynamic fluorescence quenching of the N-MoOx QDs. The sensing conditions were optimized to enhance selectivity and sensitivity. Under optimal conditions, the linear relationship between fluorescence response at 408 nm and Cu2+ concentration was determined. The linear range of this relationship was 1-100 µM. The limits of detection (LOD) and quantitation (LOQ) for Cu2+ were 0.78 µM and 2.34 µM, respectively. The method was successfully applied to detect Cu2+ in water samples with satisfactory sample recovery rates from 91.7 to 116.4%. The sensor exhibits high selectivity toward Cu2+, making it useful for environmental sample monitoring.