LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing.

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.

Trusted artificial intelligence for environmental assessments: An explainable high-precision model with multi-source big data.

Environmental assessments are critical for ensuring the sustainable development of human civilization. The integration of artificial intelligence (AI) in these assessments has shown great promise, yet the "black box" nature of AI models often undermines trust due to the lack of transparency in their decision-making processes, even when these models demonstrate high accuracy. To address this challenge, we evaluated the performance of a transformer model against other AI approaches, utilizing extensive multivariate and spatiotemporal environmental datasets encompassing both natural and anthropogenic indicators. We further explored the application of saliency maps as a novel explainability tool in multi-source AI-driven environmental assessments, enabling the identification of individual indicators' contributions to the model's predictions. We find that the transformer model outperforms others, achieving an accuracy of about 98% and an area under the receiver operating characteristic curve (AUC) of 0.891. Regionally, the environmental assessment values are predominantly classified as level II or III in the central and southwestern study areas, level IV in the northern region, and level V in the western region. Through explainability analysis, we identify that water hardness, total dissolved solids, and arsenic concentrations are the most influential indicators in the model. Our AI-driven environmental assessment model is accurate and explainable, offering actionable insights for targeted environmental management. Furthermore, this study advances the application of AI in environmental science by presenting a robust, explainable model that bridges the gap between machine learning and environmental governance, enhancing both understanding and trust in AI-assisted environmental assessments.

Efficacy and safety of microwave ablation for treatment of follicular thyroid neoplasms: a preliminary study.

OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Engineered Cell Elongation Promotes Extracellular Electron Transfer of Shewanella Oneidensis.

To investigate how cell elongation impacts extracellular electron transfer (EET) of electroactive microorganisms (EAMs), the division of model EAM Shewanella oneidensis (S. oneidensis) MR-1 is engineered by reducing the formation of cell divisome. Specially, by blocking the translation of division proteins via anti-sense RNAs or expressing division inhibitors, the cellular length and output power density are all increased. Electrophysiological and transcriptomic results synergistically reveal that the programmed cell elongation reinforces EET by enhancing NADH oxidation, inner-membrane quinone pool, and abundance of c-type cytochromes. Moreover, cell elongation enhances hydrophobicity due to decreased cell-surface polysaccharide, thus facilitates the initial surface adhesion stage during biofilm formation. The output current and power density all increase in positive correction with cellular length. However, inhibition of cell division reduces cell growth, which is then restored by quorum sensing-based dynamic regulation of cell growth and elongation phases. The QS-regulated elongated strain thus enables a cell length of 143.6 ± 40.3 µm (72.6-fold of that of S. oneidensis MR-1), which results in an output power density of 248.0 ± 10.6 mW m-2 (3.41-fold of that of S. oneidensis MR-1) and exhibits superior potential for pollutant treatment. Engineering cellular length paves an innovate avenue for enhancing the EET of EAMs.

Preclinical evaluation of reversible pulsed electrical field: electrophysiological and histological assessment of myocardium.

Background: Pulsed field ablation, as a non-thermal ablation modality, has received increasing attention. The aim of this study is to explore whether a reversible pulsed electric field (RPEF) can temporarily inhibit electrical conduction and provide a novel method for precise ablation of arrhythmia. Methods: RPEF energy was delivered from an ablation catheter to the atrium of six dogs, followed by a series of electrogram and histology assessments. Results: RPEF ablation of ordinary myocardium resulted in an average reduction of 68.3% (range, 53.7%-83.8%) in electrogram amplitude, while 5 min later, the amplitude in eight electrograms returned to 77.9% (range, 72.4%-87.3%) of baseline. Similarly, the amplitude of the sinoatrial node electrograms reduced by an average of 73.0% (range, 60.2%-84.4%) after RPEF ablation, but recovered to 84.9% (range, 80.3%-88.5%) of baseline by 5 min. No necrotic change was detected in histopathology. Transient third-degree atrioventricular block occurred following the ablation of the maximum His potential sites with RPEF, the duration of which was voltage dependent. The histopathological results showed necrosis of the myocardium at the ablation sites but no injury to His bundle cells. Conclusions: RPEF can be applied to transiently block electrical conduction in myocardial tissues contributing to precise ablation.

The interplay between metal ions and immune cells in glioma: pathways to immune escape.

This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

Epidemiological features of spinal intradural tumors, a single-center clinical study in Beijing, China.

BACKGROUND: Spinal intradural tumors are rare and heterogeneous in histological type, aggressiveness, and symptomatology, and there is a lack of data about them. This study investigated the epidemiological features of spinal intradural tumors. METHODS: This retrospective analysis included patients with spinal intradural tumors who underwent surgical treatment at the Myelopathy and Spondylosis Ward Beijing Jishuitan Hospital between January 2012 and December 2022. RESULTS: This study included 1321 patients [aged 47.19 ± 14.90 years, 603 (45.65%) males] with spinal intradural tumors. The most common histological subtype was schwannoma [n = 511 (38.68%)], followed by spinal meningioma [n = 184 (13.93%)] and ependymoma [n = 101 (7.65%)]. Fifteen (1.14%) patients were diagnosed with metastatic spinal intradural tumors as a presentation of another primary cancer type. The spinal intradural tumors were mostly found in the lumbar region [n = 436 (33.01%)], followed by the thoracic vertebrae [n = 390 (29.52%)], cervical vertebrae [n = 154 (11.66%)], and thoracolumbar region [n = 111 (8.40%)]. Schwannomas mostly affected the lumbar region [n = 256 (52.64%)], spinal meningiomas in the thoracic region [n = 153 (83.15)], and ependymomas in the lumbar region [56 (55.45%)]. The de novo metastases were mostly found in the lumbar region [n = 8 (53.33%)]. CONCLUSION: According to the results of our single-center study, the most common spinal intradural tumor in Northern China is schwannoma, followed by spinal meningioma and ependymoma.

Performance of radiomics in the differential diagnosis of parotid tumors: a systematic review.

Purpose: A systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy. Methods: Databases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model. Results: A total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions. Conclusion: There is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment.

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

The robustness of porin-cytochrome gene clusters from Geobacter metallireducens in extracellular electron transfer.

To investigate their roles in extracellular electron transfer (EET), the porin-cytochrome (pcc) gene clusters Gmet0825-0828, Gmet0908-0910, and Gmet0911-0913 of the Gram-negative bacterium Geobacter metallireducens were deleted. Failure to delete all pcc gene clusters at the same time suggested their essential roles in extracellular reduction of Fe(III)-citrate by G. metallireducens. Deletion of Gmet0825-0828 had no impact on bacterial reduction of Fe(III)-citrate but diminished bacterial reduction of ferrihydrite and abolished anode reduction and direct interspecies electron transfer (DIET) to Methanosarcina barkeri and Geobacter sulfurreducens. Although it had no impact on the bacterial reduction of Fe(III)-citrate, deletion of Gmet0908-0910 delayed ferrihydrite reduction, abolished anode reduction, and diminished DIET. Deletion of Gmet0911-0913 had little impact on DIET but diminished bacterial reductions of Fe(III)-citrate, ferrihydrite, and anodes. Most importantly, deletions of both Gmet0825-0828 and Gmet0908-0910 restored bacterial reduction of ferrihydrite and anodes and DIET. Enhanced expression of Gmet0911-0913 in this double mutant when grown in coculture with G. sulfurreducens ΔhybLΔfdnG suggested that this cluster might compensate for impaired EET functions of deleting Gmet0825-0828 and Gmet0908-0910. Thus, these pcc gene clusters played essential, distinct, overlapping, and compensatory roles in EET of G. metallireducens that are difficult to characterize as deletion of some clusters affected expression of others. The robustness of these pcc gene clusters enabled G. metallireducens to mediate EET to different acceptors for anaerobic growth even when two of its three pcc gene clusters were inactivated by mutation. The results from this investigation provide new insights into the roles of pcc gene clusters in bacterial EET. IMPORTANCE: The Gram-negative bacterium Geobacter metallireducens is of environmental and biotechnological significance. Crucial to the unique physiology of G. metallireducens is its extracellular electron transfer (EET) capability. This investigation sheds new light on the robust roles of the three porin-cytochrome (pcc) gene clusters, which are directly involved in EET across the bacterial outer membrane, in the EET of G. metallireducens. In addition to their essential roles, these gene clusters also play distinct, overlapping, and compensatory roles in the EET of G. metallireducens. The distinct roles of the pcc gene clusters enable G. metallireducens to mediate EET to a diverse group of electron acceptors for anaerobic respirations. The overlapping and compensatory roles of the pcc gene clusters enable G. metallireducens to maintain and restore its EET capability for anaerobic growth when one or two of its three pcc gene clusters are deleted from the genome.

A fast and genotype-independent in planta Agrobacterium-mediated transformation method for soybean.

Efficient genotype-independent transformation and genome editing are highly desirable for plant biotechnology research and product development efforts. We have developed a novel approach to enable fast, high-throughput, and genotype-flexible Agrobacterium-mediated transformation using the important crop soybean as a test system. This new method is called GiFT (genotype-independent fast transformation) and involves only a few simple steps. The method uses germinated seeds as explants, and DNA delivery is achieved through Agrobacterium infection of wounded explants as in conventional in vitro-based methods. Following infection, the wounded explants are incubated in liquid medium with a sublethal level of selection and then transplanted directly into soil. The transplanted seedlings are then selected with herbicide spray for 3 weeks. The time required from initiation to fully established healthy T0 transgenic events is about 35 days. The GiFT method requires minimal in vitro manipulation or use of tissue culture media. Because the regeneration occurs in planta, the GiFT method is highly flexible with respect to genotype, which we demonstrate via successful transformation of elite germplasms from diverse genetic backgrounds. We also show that the soybean GiFT method can be applied to both conventional binary vectors and CRISPR-Cas12a vectors for genome editing applications. Analyses of T1 progeny demonstrate that the events have a high inheritance rate and can be used for genome engineering applications. By minimizing the need for tissue culture, the novel approach described here significantly improves operational efficiency while greatly reducing personnel and supply costs. It is the first industry-scale transformation method to utilize in planta selection in a major field crop.

Screening Tool for Paroxysmal Atrial Fibrillation Based on a Deep-Learning Algorithm Using Printed 12-Lead Electrocardiographic Records during Sinus Rhythm.

Background: Recent advancements in artificial intelligence (AI) have significantly improved atrial fibrillation (AF) detection using electrocardiography (ECG) data obtained during sinus rhythm (SR). However, the utility of printed ECG (pECG) records for AF detection, particularly in developing countries, remains unexplored. This study aims to assess the efficacy of an AI-based screening tool for paroxysmal AF (PAF) using pECGs during SR. Methods: We analyzed 5688 printed 12-lead SR-ECG records from 2192 patients admitted to Beijing Chaoyang Hospital between May 2011 to August 2022. All patients underwent catheter ablation for PAF (AF group) or other electrophysiological procedures (non-AF group). We developed a deep learning model to detect PAF from these printed SR-ECGs. The 2192 patients were randomly assigned to training (1972, 57.3% with PAF), validation (108, 57.4% with PAF), and test datasets (112, 57.1% with PAF). We developed an applet to digitize the printed ECG data and display the results within a few seconds. Our evaluation focused on sensitivity, specificity, accuracy, F1 score, the area under the receiver-operating characteristic curve (AUROC), and precision-recall curves (PRAUC). Results: The PAF detection algorithm demonstrated strong performance: sensitivity 87.5%, specificity 66.7%, accuracy 78.6%, F1 score 0.824, AUROC 0.871 and PRAUC 0.914. A gradient-weighted class activation map (Grad-CAM) revealed the model's tailored focus on different ECG areas for personalized PAF detection. Conclusions: The deep-learning analysis of printed SR-ECG records shows high accuracy in PAF detection, suggesting its potential as a reliable screening tool in real-world clinical practice.

Efficacy and Safety of Thermal Ablation for Solitary Low-Risk T2N0M0 Papillary Thyroid Carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. RESULTS: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). CONCLUSION: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.

Individualized prediction of online shopping addiction from whole-brain functional connectivity.

Online shopping addiction (OSA) is defined as a behavioral addiction where an individual exhibits an unhealthy and excessive attachment to shopping on the Internet. Since the OSA shown its adverse impacts on individuals' daily life and social functions, it is important to examine the neurobiological underpinnings of OSA that could be used in clinical practice to identify individuals with OSA. The present study addressed this question by employing a connectome-based prediction model approach to predict the OSA tendency of healthy subjects from whole-brain resting-state functional connectivity. The OSA connectome - a set of connections across multiple brain networks that contributed to predict individuals' OSA tendency was identified, including the functional connectivity between the frontal-parietal network (FPN) and cingulo-opercular network (CON) (i.e., positive network), as well as the functional connectivity within default mode network (DMN) and that between FPN and DMN (i.e., negative network). Key nodes that contributed to the prediction model included the middle frontal gyrus, inferior frontal gyrus, anterior cingulate cortex, and inferior temporal gyrus, which have been associated with impulsivity and emotional processing. Notably, this connectome has shown its specific role in predicting OSA by controlling for the influence of general Internet addiction. Moreover, the strength of the negative network mediated the relationship between OSA and impulsivity, highlighting that the negative network underlies the impulsivity characteristic of OSA. Together, these findings advanced our understanding of the neural correlates of OSA and provided a promising framework for diagnosing OSA.

Interactive and lag effects of environmental factors on the density of schistosome-transmitting Oncomelania hupensis: A twelve-year monthly repeated survey.

Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum. We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.

Viral communities in a pH>10 serpentinite-like environment: insight into diversity and potential roles in modulating the microbiomes by bioactive vitamin B9 synthesis.

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

Goal-directed attention transforms both working and long-term memory representations in the human parietal cortex.

The abundance of distractors in the world poses a major challenge to our brain's limited processing capacity, but little is known about how selective attention modulates stimulus representations in the brain to reduce interference and support durable target memory. Here, we collected functional magnetic resonance imaging (fMRI) data in a selective attention task in which target and distractor pictures of different visual categories were simultaneously presented. Participants were asked to selectively process the target according to the effective cue, either before the encoding period (i.e., perceptual attention) or the maintenance period (i.e., reflective attention). On the next day, participants were asked to perform a memory recognition task in the scanner in which the targets, distractors, and novel items were presented in a pseudorandom order. Behavioral results showed that perceptual attention was better at enhancing target memory and reducing distractor memory than reflective attention, although the overall memory capacity (memory for both target and distractor) was comparable. Using multiple-voxel pattern analysis of the neural data, we found more robust target representation and weaker distractor representation in working memory for perceptual attention than for reflective attention. Interestingly, perceptual attention partially shifted the regions involved in maintaining the target representation from the visual cortex to the parietal cortex. Furthermore, the targets and distractors simultaneously presented in the perceptual attention condition showed reduced pattern similarity in the parietal cortex during retrieval compared to items not presented together. This neural pattern repulsion positively correlated with individuals' recognition of both targets and distractors. These results emphasize the critical role of selective attention in transforming memory representations to reduce interference and improve long-term memory performance.

Development of Novel N-Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

Impact of Pulsed Electric Field Ablation on His Bundle Conduction: A Preclinical Canine Study.

BACKGROUND Pulsed field ablation (PFA), as a non-thermal ablation modality, has received increasing attention. The aim of this study was to evaluate the effect of PFA upon His bundle via its implementation with different voltages on the maximum His bundle potential in canines, providing scientific basis for clinical application. MATERIAL AND METHODS Pulsed electrical field energy was delivered from a ablation catheter to the maximum His potential of 7 dogs, followed by a series of electrogram and histology assessments. RESULTS The baseline AH and HV intervals were 55.3±3.7 ms (range, 53.0-59.0 ms), and 34.9±1.3 ms (range, 34.0-36.0 ms), respectively, which were elevated to 65.0±5.4 ms (range, 59.0-70.0 ms) and 35.7±2.7 ms (range, 34.0-37.0 ms) after PFA. Before ablation and immediately after the recovery of third-degree AVB, the AH interval was prolonged (P<0.05) while the HV interval remained unchanged (P>0.05). After ablation, all 7 canines experienced transient third-degree AVB, with a voltage-dependent duration. Masson staining results revealed no apparent damage in His bundle cells. CONCLUSIONS Within a certain voltage range of pulse electric field, ablation of the maximum His potential in canines can result in transient third-degree AVB, providing a new route for guiding safe ablation of para-Hisian arrhythmia.

Repurposing promethazine hydrochloride to inhibit biofilm formation against Burkholderia thailandensis.

Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, an intracellular pathogen with a high mortality rate and significant antibiotic resistance. The high mortality rate and resistance to antibiotics have drawn considerable attention from researchers studying melioidosis. This study evaluated the effects of various concentrations (75, 50, and 25 µg/mL) of promethazine hydrochloride (PTZ), a potent antihistamine, on biofilm formation and lipase activity after 24 h of exposure to B. thailandensis E264. A concentration-dependent decrease in both biofilm biomass and lipase activity was observed. RT-PCR analysis revealed that PTZ treatment not only made the biofilm structure loose but also reduced the expression of btaR1, btaR2, btaR3, and scmR. Single gene knockouts of quorum sensing (QS) receptor proteins (∆btaR1, ∆btaR2, and ∆btaR3) were successfully constructed. Deletion of btaR1 affected biofilm formation in B. thailandensis, while deletion of btaR2 and btaR3 led to reduced lipase activity. Molecular docking and biological performance results demonstrated that PTZ inhibits biofilm formation and lipase activity by suppressing the expression of QS-regulated genes. This study found that repositioning PTZ reduced biofilm formation in B. thailandensis E264, suggesting a potential new approach for combating melioidosis.