Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies.

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

ANATOMIC OUTCOMES OF LENS-SPARING VITRECTOMY FOR STAGE 3 OR 4 FAMILIAL EXUDATIVE VITREORETINOPATHY.

PURPOSE: To report the anatomic outcomes and retinal structure changes from lens-sparing vitrectomy (LSV) for eyes with Stage 3 or 4 familial exudative vitreoretinopathy (FEVR). METHODS: Overall, 133 consecutive eyes of 119 patients with Stage 3 (51 eyes) or 4 (82 eyes) FEVR who underwent LSV between January 2012 and May 2023 were retrospectively reviewed. RESULTS: One hundred twenty-nine eyes (97.0%) achieved traction relief through one LSV operation. The extent of retinal detachment improved in 98 eyes (73.7%), remained stable in 32 eyes (24.1%), and progressed in three eyes (2.3%). At long-term follow-up, 39 (29.3%) and 60 (45.1%) eyes had completely or partially reattached retina, respectively. The median change of venular angle was 3.6° (95% CI, 3.5-10.5; P < 0.001) and -9.9° (95% CI, -15.8 to -4.6; P < 0.001) for temporal and nasal vessels, respectively. The mean disk-fovea distance was 0.3 papillary diameter shorter (95% CI, -0.4 to -0.2; P < 0.001), and the mean temporal venular arcade distance was 0.02 papillary diameter larger (95% CI, -0.16 to 0.21; P = 0.361). CONCLUSION: These results suggest that LSV can relieve vitreoretinal traction and reattach the retina in late-stage FEVR eyes. Improvements in temporal and nasal venular angle and disk-fovea distance reflect positive retinal structure changes for patients.

A pumpless liver-on-a-chip for drug hepatotoxicity analysis.

This study presents the development and validation of an innovative microfluidic liver-on-a-chip device utilizing gravity-driven perfusion for the evaluation of drug hepatotoxicity. This research involved the construction of a hydrogel-based coculture chip that integrates liver parenchymal and stellate cells within a tri-channel configuration. The assembly and operation of the liver-on-a-chip and its accompanying custom rocker were straightforward. The cells in the chip maintained high viability and continuously synthesized liver albumin over extended culture durations. Acetaminophen (APAP), a hepatic injury-inducing drug, was utilized as a positive control in hepatic toxicity assays on the chip. The liver chip exhibited hepatotoxic responses comparable to those observed in 2D models. Furthermore, in this study we evaluated the effects of two plant-derived natural compounds, aristolochic acid I (AA) and its analog aristolactam AII (AL), in both 2D cell models and the liver-on-a-chip system. AA, known for its hepatorenal toxicity, was observed to cause hepatotoxicity in both the 2D models and on the chip. The flow cytometry and mRNA sequencing results confirmed the propensity of these compounds to induce liver cell apoptosis. Notably, AL, previously considered nontoxic, provoked a significant decrease in the hepatic functionality marker albumin exclusively in the liver chip but not in 2D models, indicating the liver chip's enhanced sensitivity to toxic substances. In summary, this pumpless liver-on-a-chip is a simple yet powerful tool for drug hepatotoxicity studies.

Comparative analysis of microbial community under acclimation of linear alkylbenzene sulfonate (LAS) surfactants and degradation mechanisms of functional strains.

Linear alkylbenzene sulfonate (LAS) is one of the most widely used anionic surfactants and a common toxic pollutant in wastewater. This study employed high throughput sequencing to explore the microbial community structure within activated sludge exposed to a high concentration of LAS. Genera such as Pseudomonas, Aeromonas, Thauera and Klebsiella exhibited a significant positive correlation with LAS concentrations. Furthermore, Comamonas and Klebsiella were significantly enriched under the stress of LAS. Moreover, bacterial strains with LAS-degrading capability were isolated and characterized to elucidate the degradation pathways. The Klebsiella pneumoniae isolate L1 could effectively transform more than 60 % of 25 mg/L of LAS within 72 h. Chemical analyses revealed that L1 utilized the LAS sulfonyl group as a sulfur source to support its growth. Genomic and transcriptomic analyses suggested that strain L1 may uptake LAS through the sulfate ABC transport system and remove sulfonate with sulfate and sulfite reductases.

Single-Cell RNA Sequencing Reveals a Unique Fibroblastic Subset and Immune Disorder in Lichen Sclerosus Urethral Stricture.

Purpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair. Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.

Denitrificimonas halotolerans sp. nov., a novel species isolated from UASB sludge treating landfill leachate.

A Gram-stain-negative, facultative anaerobe, rod-shaped strain JX-1T was isolated from UASB sludge treating landfill leachate in Wuhan, China. The isolate is capable of growing under conditions of pH 6.0-11.0 (optimum, pH 7.0-8.0), temperature 4-42 â„ƒ (optimum, 20-30 â„ƒ), 0-8.0% (w/v) NaCl (optimum, 5.0%), and ammonia nitrogen concentration of 200-5000 mg/L (optimum, 500 mg/L) on LB plates. The microorganism can utilize malic acid, D-galactose, L-rhamnose, inosine, and L-glutamic acid as carbon sources, but does not reduce nitrates and nitrites. The major fatty acids are C18:1ω7c/C18:1ω6c, iso-C15:0, and anteiso-C15:0. The respiratory quinones are Q9 (91.92%) and Q8 (8.08%). Polar lipids include aminolipid, aminophospholipid, diphosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylglycerol, and phospholipid. Compared with other strains, strain JX-1T and Denitrificimonas caeni HY-14T have the highest values in terms of 16S rRNA gene sequence similarity (96.79%), average nucleotide identity (ANI; 76.06%), and average amino acid identity (AAI; 78.89%). Its digital DNA-DNA hybridization (dDDH) result is 20.3%. The genome of strain JX-1T, with a size of 2.78 Mb and 46.12 mol% G + C content, lacks genes for denitrification and dissimilatory nitrate reduction to ammonium (DNRA), but contains genes for ectoine synthesis as a secondary metabolite. The results of this polyphasic study allow genotypic and phenotypic differentiation of the analysed strain from the closest related species and confirm that the strain represents a novel species within the genus Denitrificimonas, for which the name Denitrificimonas halotolerans sp. nov. is proposed with JX-1T (= MCCC 1K08958T = KCTC 8395T) as the type strain.

PAX2 mediated upregulation of ESPL1 contributes to cisplatin resistance in bladder cancer through activating the JAK2/STAT3 pathway.

Extra spindle-polar body like 1 (ESPL1) is associated with the development of a variety of cancers, including bladder cancer, and is closely related to chemoresistance. In this study, we aimed to reveal the role of ESPL1 in bladder cancer progression and cisplatin (DDP) resistance. First, ESPL1 was found to be highly expressed in tumor tissues and cells of bladder cancer, and more highly expressed in cisplatin resistant tumor tissues or cells. The binding of PAX2 in ESPL1 promoter region was predicted by Jaspar database and verified by Ch-IP analysis and the luciferase reporter gene assay. Next, cisplatin-resistant T24 cells (T24/DDP) were established and transfected with ESPL1 siRNA (si-ESPL1) or overexpression vector (pcDNA-ESPL1) or co-transfected with PAX2 siRNA (si-PAX2) or overexpression vector (pcDNA-PAX2), and then treated with DDP or AG490, an inhibitor of JAK2. The results showed that silencing ESPL1 significantly reduced T24/DDP cell viability, colony formation and invasion, enhanced sensitivity to DDP, and induced cell apoptosis. Silencing PAX2 decreased ESPL1 expression, enhanced sensitivity to DDP, and induced apoptosis of T24/DDP cells, and inhibited activation of JAK2/STAT3 pathway. Overexpressing ESPL1 reversed the effect of PAX2 silencing on T24/DDP cells, while AG490 counteracted the reversal effect of overexpressing ESPL1. Finally, a xenograft tumor model was established and found that silencing ESPL1 or DDP treatment inhibited tumor growth, while silencing ESPL1 combined with DDP treatment had the best effect. In summary, this study suggested that PAX2-mediated ESPL1 transcriptional activation enhanced cisplatin resistance in bladder cancer by activating JAK2/STAT3 pathway.

Parachitinimonas caeni gen. nov., sp. nov., a novel member of family Burkholderiaceae isolated from activated sludge collected in Shenzhen, PR China.

A Gram-stain-negative, strictly aerobic and filamentous bacterial strain, designated as DQS-5T, was isolated from the activated sludge of a municipal sewage treatment plant in Shenzhen, PR China. Optimal growth was observed at 28 °C and pH 7.5. Catalase and oxidase activities were detected. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DQS-5T was most closely related to the genera Chitinimonas and Chitinivorax (91.0-93.4 % and 92.5 % 16S rRNA gene sequence similarity, respectively) and was close to the member of the family Burkholderiaceae. The complete genome sequence of strain DQS-5T contains 5 653 844 bp and 57.3 mol% G+C. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between the genome of strain DQS-5T and those of its close relatives were 75.9-77.2, 19.0-20.3 and 57.2-61.8 %, respectively. Chemotaxonomic analysis of strain DQS-5T indicated that the sole respiratory quinone was ubiquinone-8, the predominant cellular fatty acids were C16 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), and the major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, aminophospholipid and aminolipid. The phylogenetic, genotypic, phenotypic and chemotaxonomic data demonstrate that strain DQS-5T represents a novel species in a novel genus within the family Burkholderiaceae, for which the name Parachitinimonas caeni gen. nov., sp. nov., is proposed. Strain DQS-5T (=KCTC 92788T=CCTCC AB 2022320T) is the type and only strain of P. caeni.

Edaravone dexborneol alleviates cerebral ischemia-reperfusion injury through NF-κB/NLRP3 signal pathway.

Inflammatory injury following ischemia-reperfusion (I/R) severely limits the efficacy of stroke treatment. Edaravone dexborneol (C.EDA) has been shown to reduce inflammation following a cerebral hemorrhage. However, the precise anti-inflammatory mechanism of C.EDA is unknown. In this study, we investigated whether C.EDA provides neuroprotection after I/R in rats, as well as the potential mechanisms involved. A middle cerebral artery occlusion/reperfusion (I/R) model was created using Sprague-Dawley rats. The blood flow of the central cerebral artery was monitored by a laser speckle imaging system. The neurological score was used to assess behavioral improvement. Cerebral infarction volume was measured by TTC staining. And the integrity of the blood-brain barrier was detected by Evan's blue staining. The expression of the nuclear factor kappa-B (NF-κB)/ the NOD-like receptor protein (NLRP3) inflammasome signal pathway and microglia polarization were detected by immunofluorescence and Western blotting. The cerebral blood flow ratio indicates that the cerebral I/R model was successfully established. After reperfusion for 72 h, the improvement of neurological scores, infarct volume reduction, and integrity of the blood-brain barrier was observed in I/R rats with C.EDA treatment. Meanwhile, the immunofluorescence result showed that the expression of iNOS, NLRP3, and NF-κB protein was decreased and the level of Arg1 was increased. Western blot analysis showed that the expression of NF-κB/NLRP3 signal pathway-related protein was decreased. In conclusion, this study indicates that C.EDA alleviates I/R injury by blocking the activation of the NLRP3 inflammasome and regulating the polarization of M1/M2 microglia via the NF-κB signal pathway.

P2Y12 receptor mediates apoptosis and demyelination to affect functional recovery in mice with spinal cord injury.

Among diseases of the central nervous system (CNS), spinal cord injury (SCI) has a high fatality rate. It has been proven that P2Y G protein-coupled purinergic receptors have a neuroprotective role in apoptosis and regeneration inside the damaged spinal cord. The P2Y12 receptor (P2Y12R) has recently been linked to peripheral neuropathy and stroke. However, the role of P2Y12R after SCI remains unclear. Our study randomly divided C57BL/6J female mice into 3 groups: Sham+DMSO, SCI+DMSO, and SCI+MRS2395. MRS2395 as a P2Y12R inhibitor was intraperitoneally injected at a dose of 1.5 mg/kg once daily for 7 days. We showed that the P2Y12R was markedly activated after injury, and it was double labeled with the microglial and neuron. Behavioral tests were employed to assess motor function recovery. By using immunofluorescence staining, the NeuN expression level was detected. The morphology of neurons was observed by hematoxylin-eosin and Nissl staining. P2Y12R, Bax, GFAP, PCNA and calbindin expression levels were detected using Western blot. Meanwhile, mitochondria and myelin sheath were observed by transmission electron microscopy (TEM). Our findings demonstrated that MRS2395 significantly enhanced motor function induced by SCI and that was used to alleviate apoptosis and astrocyte scarring. NeuN positive cells in the SCI group were lower than in the therapy group, although Bax, GFAP, PCNA and calbindin expression levels were considerably higher. Moreover, following MRS2395 therapy, the histological damage was reversed. A notable improvement in myelin sheath and mitochondrial morphology was seen in the therapy group. Together, our findings indicate that activation of P2Y12R in damaged spinal cord may be a critical event and suggest that inhibition of P2Y12R might be a feasible therapeutic strategy for treating SCI.

Tessaracoccus caeni sp. nov., a novel member of Propionibacteriaceae isolated from activated sludge in Hefei, PR China.

A floc-forming bacterial strain, designated HF-7T, was isolated from the activated sludge of an industrial wastewater treatment plant in Hefei, PR China. Cells of this strain were Gram-stain-positive, catalase- and oxidase-negative, facultatively anaerobic, and rod-shaped. Growth occurred at 20-42 °C (optimum, 28 °C), at pH 5.5-10.5 (optimum, pH 7.5) and with 0-8.0 % (w/v) NaCl (optimum, 1 %). The major fatty acid was anteiso-C15 : 0. The polar lipid profile contained phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The DNA G+C content was 67 mol% from whole genomic sequence analysis. Based on the results of 16S rRNA gene sequence analysis, this strain should be assigned to the genus Tessaracoccus and is closely related to Tessaracoccus arenae CAU 1319T (95.87 % similarity), Tessaracoccus lapidicaptus IPBSL-7T (95.19 %) and Tessaracoccus bendigoensis Ben 106T (94.63 %) but separated from them by large distances in different phylogenetic trees. Based on whole genome analysis, the orthologous average nucleotide identity and in silico DNA-DNA hybridization values against two of the closest relatives were 75.21-76.50 % and 14.2-24.4 %, respectively. The phylogenetic, genotypic, phenotypic and chemotaxonomic data demonstrated that strain HF-7T could be distinguished from its phylogenetically related species and represents a novel species within the genus Tessaracoccus, for which the name Tessaracoccus caeni sp. nov. is proposed. The type strain is HF-7T (=KCTC 49959T=CCTCC AB 2023019T).

Genomic similarity and antibody-dependent enhancement of immune serum potentially affect the protective efficacy of commercial MLV vaccines against NADC30-like PRRSV.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide. The PRRSV mutation rate is the highest among the RNA viruses. To date, NADC30-like PRRSV and highly pathogenic PRRSV (HP-PRRSV) are the dominant epidemic strains in China; however, commercial vaccines do not always provide sufficient cross-protection, and the reasons for insufficient protection are unclear. This study isolated a wild-type NADC30-like PRRSV, SX-YL1806, from Shaanxi Province. Vaccination challenge experiments in piglets showed that commercial modified live virus (MLV) vaccines provided good protection against HP-PRRSV. However, it could not provide sufficient protection against the novel strain SX-YL1806. To explore the reasons for this phenomenon, we compared the genomic homology between the MLV strain and HP-PRRSV or NADC30-like PRRSV and found that the MLV strain had a lower genome similarity with NADC30-like PRRSV. Serum neutralization assay showed that MLV-immune serum slightly promoted the homologous HP-PRRSV replication and significantly promoted the heterologous NADC30-like PRRSV strain replication in vitro, suggesting that antibody-dependent enhancement (ADE) might also play a role in decreasing MLV protective efficacy. These findings expand our understanding of the potential factors affecting the protective effect of PRRSV MLV vaccines against the NADC30-like strains.

Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury.

Ferroptosis is a newly defined form of cell death involved in neurologic disease. Resveratrol is a non-flavonoid polyphenolic compound with anti-inflammatory and antioxidant properties, but its potential therapeutic mechanism in spinal cord injury (SCI) remains unknown. Therefore, this study evaluates the mechanism by which resveratrol promotes neurological and motor function recovery in mice with SCI. The motor function of mice was evaluated using the Basso Mouse Scale score and footprint test. The effect of resveratrol on the neuronal cell state was observed using NeuN, fluoro-Jade C, and Nissl staining. The expression of iron content in injured segments was observed using Perls blue and Diaminobenzidine staining. The effect of resveratrol on the levels of malondialdehyde, glutathione, Fe2+ , and glutathione peroxidase 4 enzyme activity was also investigated. The mitochondrial ultrastructures of injured segment cells were observed using transmission electron microscope, while the protein levels of ferroptosis-related targets were detected using Western blot. Our findings show that resveratrol improves motor function after SCI and has certain neuroprotective effects; in ferroptosis-related studies, resveratrol inhibited the expression of ferroptosis-related proteins and ions. Resveratrol improved changes in mitochondrial morphology. Mechanistically, the Nrf2 inhibitor ML385 reversed the inhibitory effect of resveratrol on ferroptosis-related genes, indicating that resveratrol inhibits ferroptosis through the Nrf2/GPX4 pathway. Our findings elucidate that resveratrol promotes functional recovery, inhibits ferroptosis post-SCI, and provides an experimental basis for subsequent clinical translational research. Our study shows that resveratrol inhibits the production of lipid peroxide and the accumulation of iron by activating Nrf2/GPX4 signaling pathway, thereby inhibiting neuronal ferroptosis. At the same time, it can promote the recovery of motor function of mice.

Proactive health interventions in the workplace: The role of spatial playfulness in promoting mental health.

BACKGROUND: The high prevalence of mental illnesses has a serious impact on productive life and there is an urgent need to intervene using a variety of active and effective measures. OBJECTIVE: The concept of playfulness in space is introduced into the design of work spaces oriented towards active health interventions, creating a close interaction between the body and the space through play, thus developing a positive effect on the promotion of the physical and mental health of the staff. METHODS: With the help of the spatial order theory, the analysis of the interaction between body and space is attempted to explore the form, structure and scene of space in order to optimize the body's perception, cognition and behavior in the space, thus creating an indoor workspace model with positive intervention effects on human health. RESULTS: Based on the idea of spatial playful participation in active health interventions, this study explores the interaction between the body and the architectural space to enhance the perception and cognitive guidance of the space for the individual and to have a pleasant spiritual experience in the interaction to relieve work stress and enhance mental health. CONCLUSION: This series of discussions on the relationship between architectural space and the human body is of great relevance in improving the public health of occupational groups.

Prophylactic inguinal lymphadenectomy for high-risk cN0 penile cancer: The optimal surgical timing.

Background: Few reports have investigated the oncologically safe timing of prophylactic inguinal lymphadenectomy for penile cancer patients with clinically normal inguinal lymph nodes (cN0), particularly those who received delayed surgical treatment. Methods: The study included pT1aG2, pT1b-3G1-3 cN0M0 patients with penile cancer who received prophylactic bilateral inguinal lymph nodes dissection (ILND) at the Department of Urology of Tangdu Hospital between October 2002 and August 2019. Patients who received simultaneous resection of primary tumor and inguinal lymph nodes were assigned to the immediate group, while the rest were assigned to the delayed group. The optimal timing of lymphadenectomy was determined based on the time-dependent ROC curves. The disease-specific survival (DSS) was estimated based on the Kaplan-Meier curve. Cox regression analysis was used to evaluate the associations between DSS and the timing of lymphadenectomy and tumor characteristics. The analyses were repeated after stabilized inverse probability of treatment weighting adjustment. Results: A total of 87 patients were enrolled in the study, 35 of them in the immediate group and 52 in the delayed group. The median (range) interval time between primary tumor resection and ILND of the delayed group was 85 (29-225) days. Multivariable Cox analysis demonstrated that immediate lymphadenectomy was associated with a significant survival benefit (HR, 0.11; 95% CI, 0.02-0.57; p = 0.009). An index of 3.5 months was determined as the optimal cut-point for dichotomization in the delayed group. In high-risk patients who received delayed surgical treatment, prophylactic inguinal lymphadenectomy within 3.5 months was associated with a significantly better DSS compared to dissection after 3.5months (77.8% and 0%, respectively; log-rank p<0.001). Conclusions: Immediate and prophylactic inguinal lymphadenectomy in high-risk cN0 patients (pT1bG3 and all higher stage tumours) with penile cancer improves survival. For those patients at high risk who received delayed surgical treatment for any reason, within 3.5 months after resection of the primary tumor seems to be an oncologically safe window for prophylactic inguinal lymphadenectomy.

Emergence of lnu(C) variant conferring lincomycin resistance in Campylobacter coli of chicken origin.

Lincomycin is widely used in respiratory and gastrointestinal infection in veterinary medicine and food animal production. Campylobacter members are vital foodborne pathogens causing campylobacteriosis, and the resistance to lincosamides is seldom reported. To date, only the rRNA methyltransferase Erm(B) has been confirmed to be associated with lincosamides resistance in Campylobacter. In this study, we identified a lnu(C) variant conferring lincomycin resistance in this pathogen of chicken origin. The Lnu(C) encoded by this gene variant showed substitution at position 8 (Asn8Lys), 11 (Phe11Leu) and 112 (Leu112Phe), when compared with the firstly reported Lnu(C) from Streptococcus agalactiae. Cloning of the lnu(C) variant into lincosamide-susceptible Campylobacter jejuni NCTC 11168 confirmed its function in conferring resistance to lincomycin with the 32-fold increased MICs. Sequencing analysis showed that the lnu(C) variant was located within a MTnSag1-like transposon together with insLNU, which is inserted between panB and cj0299 genes on the chromosome. lnu(C) gene was distributed among C. coli globally, and various STs were involved in the dissemination of lnu(C). Although transposition mediated by MTnSag1-like transposon failed to occur, the horizontal transfer mediated by natural transformation and reservoir for resistance genes may facilitate their adaptation to the antimicrobial selection pressure in chickens, which should not be ignored.

Quercetin alleviates subarachnoid hemorrhage-induced early brain injury via inhibiting ferroptosis in the rat model.

Early brain injury (EBI) refers to a series of pathophysiological brain lesions that occur within 72 hr after subarachnoid hemorrhage (SAH), which is an extremely crucial factor in the poor prognosis of patients. In EBI, ferroptosis has been proven to cause neuronal death. Quercetin (QCT) is effective in deactivating reactive oxygen species (ROS), inhibiting lipid peroxidation, and even chelating iron, but its role in SAH remains unclear. In this study, the mortality rate, severity grade of SAH, brain water content (BWC), blood-brain barrier permeability, and neurological function of the rats were detected. Moreover, mitochondrial morphology in cortical neurons were observed and their sizes were subsequently quantified. The levels of lipid peroxidation on glutathione and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined, whereas the protein expressions of glutathione peroxidase 4 (GPX4), SLC7A11 (xCT), transferrin receptor 1 (TfR1), and ferroportin-1 (FPN1) were analyzed by western immunoblotting. The neurodegeneration involved in EBI was investigated by fluoro-Jade C staining, while iron staining was utilized to measure iron content. Our results showed that inhibition of ferroptosis by QCT could suppress EBI and improve neurological function in SAH rats. QCT increased the expression levels of GPX4, xCT, and FPN1, while downregulated TfR1, and exerted protective effects on neurons as well as alleviated iron accumulation and lipid peroxidation in the cortex of SAH rats. In conclusion, our study revealed that QCT might alleviate the EBI by inhibiting ferroptosis in SAH rats.

A randomized controlled trial of positive end-expiratory pressure on pulmonary oxygenation and biventricular function in esophageal cancer patients receiving one-lung ventilation under a lower FiO2.

Background: Arterial oxygenation is often impaired during one-lung ventilation (OLV), due to both pulmonary shunt and atelectasis. Lower fraction of inspiration O2 (FiO2) may reduce inflammation and complications, but may increase the risk of hypoxemia. The aim of this randomized controlled parallel trial was to analyze whether higher positive end-expiratory pressure (PEEP) could improve oxygenation and maintain lower levels of inflammation during OLV under a lower FiO2. Methods: One hundred and twenty patients with selective thoracotomy for esophageal cancer (EC) were classified randomly into four groups on a ratio of 1:1:1:1 using a computer-generated list, including Group A (FiO2 =0.6, PEEP =0), Group B (FiO2 =0.6, PEEP =5 cmH2O), Group C (FiO2 =1.0, PEEP =8 cmH2O), and Group D (FiO2 =1.0, PEEP =10 cmH2O). The oxygenation and pulmonary shunt were primary outcomes. Haemodynamics, respiratory mechanics, serum IL-6 and IL-10 levels, and complications were taken as secondary outcomes. Follow-up was terminated until discharge. Results: Two patients in Group A and two in Group D were excluded due to hypoxemia and hypotension, respectively. Then the data of 116 patients (Group A =28, Group B =30 Group C =30, and Group D =28) were assessed for final analysis. Compared with Group B, the partial pressure of oxygen (PaO2) and dynamic compliance during OLV in Group D were significantly increased from 15 minutes to 60 minutes, while pulmonary shunt was significantly decreased (P>0.05). Patients in Group D had higher levels of central venous pressure (CVP) and airway pressure (Paw) during OLV and higher levels of IL-6 and IL-10 after OLV compared with Group B (P>0.05). No statistical differences were found in oxygen saturation (SaO2), PvO2 (partial pressure of oxygen in venous blood), partial pressure of end-tidal carbon dioxide (ETCO2), partial pressure of carbon dioxide in artery (PaCO2), heart rate (HR), mean arterial pressure (MAP), and complications among the four groups (P>0.05). Conclusions: Higher PEEP increased the oxygenation under 60% O2 during OLV. However, the haemodynamics and respiratory mechanics changed, and the levels of inflammation increased. A higher PEEP under 60% O2 during OLV is not recommended. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900024726.

The 980 nm diode laser treatment for non-muscle-invasive bladder tumor with en bloc technique: single-center experience.

BACKGROUND: Transurethral resection of the bladder tumor (TURBT) is one of the most established urological procedures for the treatment of the primary non-muscle-invasive bladder cancer (NMIBC). The aim of the study is to evaluate the efficacy and safety of 980 nm diode laser as a treatment for primary NMIBC. METHODS: Eighty-eight patients with NMIBC were treated by en bloc transurethral resection with 980 nm diode laser, and 76 patients were treated by plasmakinetic transurethral resection from May 2016 to July 2019 at the Department of Urology, Tangdu Hospital, Air Force Medical University. The clinical data were collected and compared between the two groups. RESULTS: The bladder irrigation time was shortened in 980 nm diode laser group compared to that of plasmakinetic transurethral resection group (4.1 ± 0.6 vs 13.1 ± 3.1 h, p < 0.001). A total of 13.2% (10/76) patients experienced obturator nerve reflex, and 5.3% (4/76) experienced delayed bleeding in plasmakinetic transurethral resection group, while no obturator nerve reflex and delayed bleeding cases were observed in 980 nm diode laser group (p < 0.05). The postoperative catheterization and hospitalization time showed no significant difference between the two groups. The median follow-up time was 27 months (13-38 months). No significant difference in the recurrence rate was observed between the two groups. CONCLUSIONS: The 980 nm diode laser is an effective and safe tool in transurethral resection of NMIBC using en bloc technique. It has less perioperative complications and shortened bladder irrigation time.

A rapid method for isolation of bacterial extracellular vesicles from culture media using epsilon-poly-L-lysine that enables immunological function research.

Both Gram-negative and Gram-positive bacteria can release vesicle-like structures referred to as bacterial extracellular vesicles (BEVs), which contain various bioactive compounds. BEVs play important roles in the microbial community interactions and host-microbe interactions. Markedly, BEVs can be delivered to host cells, thus modulating the development and function of the innate immune system. To clarify the compositions and biological functions of BEVs, we need to collect these vesicles with high purity and bioactivity. Here we propose an isolation strategy based on a broad-spectrum antimicrobial epsilon-poly-L-lysine (ϵ-PL) to precipitate BEVs at a relatively low centrifugal speed (10,000 × g). Compared to the standard ultracentrifugation strategy, our method can enrich BEVs from large volumes of media inexpensively and rapidly. The precipitated BEVs can be recovered by adjusting the pH and ionic strength of the media, followed by an ultrafiltration step to remove ϵ-PL and achieve buffer exchange. The morphology, size, and protein composition of the ϵ-PL-precipitated BEVs are comparable to those purified by ultracentrifugation. Moreover, ϵ-PL-precipitated BEVs retained the biological activity as observed by confocal microscopy studies. And THP-1 cells stimulated with these BEVs undergo marked reprogramming of their transcriptome. KEGG analysis of the differentially expressed genes showed that the signal pathways of cellular inflammatory response were significantly activated. Taken together, we provide a new method to rapidly enrich BEVs with high purity and bioactivity, which has the potential to be applied to BEVs-related immune response studies.