Synergism of Light-Induced [4 + 4] Cycloaddition and Electron Transfer Toward Switchable Photoluminescence and Single-Molecule Magnet Behavior in a Dy4 Cubane.

Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.

Important role of Bacillus subtilis as a probiotic and vaccine carrier in animal health maintenance.

Bacillus subtilis is a widespread Gram-positive facultative aerobic bacterium that is recognized as generally safe. It has shown significant application value and great development potential in the animal farming industry. As a probiotic, it is frequently used as a feed growth supplement to effectively replace antibiotics due to its favourable effects on regulating the intestinal flora, improving intestinal immunity, inhibiting harmful microorganisms, and secreting bioactive substances. Consequently, the gut health and disease resistance of farmed animals can be improved. Both vegetative and spore forms of B. subtilis have also been utilized as vaccine carriers for delivering the antigens of infectious pathogens for over a decade. Notably, its spore form is regarded as one of the most prospective for displaying heterologous antigens with high activity and stability. Previously published reviews have predominantly focused on the development and applications of B. subtilis spore surface display techniques. However, this review aims to summarize recent studies highlighting the important role of B. subtilis as a probiotic and vaccine carrier in maintaining animal health. Specifically, we focus on the beneficial effects and underlying mechanisms of B. subtilis in enhancing disease resistance among farmed animals as well as its potential application as mucosal vaccine carriers. It is anticipated that B. subtilis will assume an even more prominent role in promoting animal health with in-depth research on its characteristics and genetic manipulation tools.

Comparative outcomes of video-assisted thoracoscopic surgery versus open surgery for bronchogenic cysts in adults: a retrospective cohort study.

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.

A Causal Regulation Modeling Algorithm for Temporal Events with Application to Escherichia coli's Aerobic to Anaerobic Transition.

Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli's (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.

The rate-pressure product combined model within 24 h on admission predicts the 30-day mortality rate in conservatively treated patients with intracerebral hemorrhage.

Background and objectives: Recently, some literature has proposed new indicators such as rate-pressure product, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, etc. However, there has been no literature that has utilized these new indicators to establish a predictive model for assessing the risk of mortality in patients within 24 h on admission. Therefore, this study aims to build a predictive model that can rapidly assess the likelihood of mortality in patients within 24 h of admission. Methods: The datasets used in this study are available from the corresponding author upon reasonable request. Patients were randomly assigned to the training or validation cohort based on a ratio of 7:3, which was implemented as internal validations for the final predictive models. In the training set, least absolute shrinkage and selection operator (LASSO) regression was employed to select predictive factors, followed by both univariate and subsequent multivariate analysis. The predictive ability was assessed by the area under the receiver operating characteristic (ROC) curve. Results: A total of 428 patients were included in our research. The final model included 4 independent predictors (Glasgow Coma Scale, hematoma volume, rate-pressure product, c-reactive protein) and was developed as a simple-to-use nomogram. The training set and internal validation set model's C-index are 0.933 and 0.954, demonstrating moderate predictive ability with regard to risks of mortality. Compared to ICH score (AUC: 0.910 and 0.925), the net reclassification index (NRI) is 0.298 (CI = -0.105 to 0.701, p: 0.147) and integrated discrimination improvement (IDI) is 0.089 (CI = -0.049 to 0.228, p: 0.209). Our model is equally excellent as the classic ICH score model. Conclusion: We developed a model with four independent risk factors to predict the mortality of ICH patients. Our predictive model is effective in assessing the risk of mortality in patients within 24 h on admission, which might be worth considering in clinical settings after further external validation.

HIST1H2BK predicts neoadjuvant-chemotherapy response and mediates 5-fluorouracil resistance of gastric cancer cells.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is routinely used to treat patients with advanced gastric cancer (AGC). However, the identification of reliable markers to determine which AGC patients would benefit from NACT remains challenging. METHODS: A systematic screening of plasma proteins between NACT-sensitive and NACT-resistant AGC patients was performed by a mass spectrometer (n = 6). The effect of the most differential plasma protein was validated in two independent cohorts with AGC patients undergoing NACT (ELISA cohort: n = 155; Validated cohort: n = 203). The expression of this candidate was examined in a cohort of AGC tissues using immunohistochemistry (n = 34). The mechanism of this candidate on 5-Fluorouracil (5-FU) resistance was explored by cell-biology experiments in vitro and vivo. RESULTS: A series of differential plasma proteins between NACT-sensitive and NACT-resistant AGC patients was identified. Among them, plasma HIST1H2BK was validated as a significant biomarker for predicting NACT response and prognosis. Moreover, HIST1H2BK was over-expression in NACT-resistant tissues compared to NACT-sensitive tissues in AGC. Mechanistically, HIST1H2BK inhibited 5-FU-induced apoptosis by upregulating A2M transcription and then activating LRP/PI3K/Akt pathway, thereby promoting 5-FU resistance in GC cells. Intriguingly, HIST1H2BK-overexpressing 5-FU-resistant GC cells propagated resistance to 5-FU-sensitive GC cells through the secretion of HIST1H2BK. CONCLUSION: This study highlights significant differences in plasma protein profiles between NACT-resistant and NACT-sensitive AGC patients. Plasma HIST1H2BK emerged as an effective biomarker for achieving more accurate NACT in AGC. The mechanism of intracellular and secreted HIST1H2BK on 5-FU resistance provided a novel insight into chemoresistance in AGC.

LINC01133 contributes to the malignant phenotypes of non-small cell lung cancer by targeting miR-30b-5p/FOXA1 pathway.

This study aimed to explore the mechanism of action of LINC01133 in non-small cell lung cancer. LINC01133 expression in NSCLC patient tissues and cells was detected by qRT-PCR. After transfecting siRNA-LINC01133 in NSCLC cells, the proliferation and invasive migration ability of the cells were assessed via CCK-8 and Transwell assay, respectively. The sublocalization of LINC01133 in NSCLC cells was analyzed by bioinformatics prediction and nucleoplasm separation assay and RNA-FISH assay. Analysis of the binding relationship between LINC01133, FOXA1 and miR-30b-5p was all through bioinformatics website analysis, dual-luciferase reporter and RNA Pulldown assay. Functional rescue experiments confirmed the character of miR-30b-5p and FOXA1 in LINC01133 regulating the NSCLC cells biological behavior. LINC01133 high expressions were found in NSCLC tissues and cells. siRNA-LINC01133 treatment inhibited NSCLC cells malignant behavior. Mechanistically: LINC01133 promoted FOXA1 expression through adsorption binding of miR-30b-5p. Knocking down miR-30b-5p expression or up-regulating FOXA1 expression was able to reverse siRNA-LINC01133 inhibitory effect of tumor cell malignant behavior. LINC01133 promoted FOX1 expression by competitively binding miR-30b-5p, which attenuated the targeting inhibitory effect of miR-30b-5p on FOXA1 and ultimately promoted proliferation and invasive migration of NSCLC cells.

LINC00472 suppresses non-small cell lung cancer progression via regulating miR-23a-3p/CCL22 axis.

Long non-coding RNA (lncRNA) LINC00472 has a close connection with the development of tumors. The aim was to explore the role of LINC00472 on NSCLC cell biological function in vivo and its potential mechanisms. The mRNA levels of LncRNA 00472 and microRNA-23a-3p, were determined by RT-qPCR. Cell Counting Kit-8, cell scratches and western blot assays were used to analyze the proliferation, migration and level of apoptosis-associated proteins. Luciferase reporter assay validates the binding between LINC00472/CCL22 and miR-23a-3p. LINC00472 and CCL22 were lowly expressed in NSCLC tissues and cells, while miR-23a-3p expression was upregulated. LINC00472 overexpression significantly depressed NSCLC cell cellular behavior, whereas promoting cell death. MiR-23a-3p could reverse these above-mentioned biological behavior changes caused by LINC00472 overexpression. Additionally, LINC00472 increased CCL22 expression through sponging miR-23a-3p. Knocking down CCL22 antagonized the inhibitory effect of LINC00472 on NSCLC cell survival. LINC00472 may reduce the cellular growth, and accelerate death of NSCLC through increasing CCL22 expression by targeting miR-23a-3p.

Revealing the Molecular Mechanism of Sageretia theezans in the Treatment of Hemorrhoids based on Network Pharmacology.

OBJECTIVE: Sageretia theezans is one of the classic medicines in ancient times, which is commonly used to treat scabies, lacquer sores, acute and chronic pharyngitis, Tonsillitis, Cholecystitis, secondary infection of hemorrhoids, and other symptoms. However, the potential molecular mechanism of Sageretia theezans is still unclear. In this study, we explored the active compounds of Sageretia theezans in the treatment of hemorrhoids (HD), predicted the potential targets of drugs, and verified their functions through network pharmacology and in vivo and in vitro experiments. METHODS: First, we identified the active compounds and key targets of Sageretia theezans in treating HD through network pharmacology. The key signaling pathways related to the role of Sageretia theezans were analyzed. HUVEC Human umbilical vein endothelial cells were used to study the function of Sageretia theezans and its target in vitro. In addition, we also used the SD rat hemorrhoid model to explore the efficacy of Sageretia theezans in HD in vivo. RESULT: A total of 159 drug targets were obtained from the TCMSP, ETCM, and PubChem databases. Constructing a drug component target network; differential analysis using sequencing data identified 1046 differentially expressed genes. Intersecting drug targets and differentially expressed genes obtained four intersection targets (GOT1, SLC25A10, SUCLG1, CLEC4E). Perform single gene GSEA functional enrichment analysis on intersection targets, select KEGG and GO of the top 10 for display, and merge the results. In order to investigate the interaction between intersecting genes and differentially expressed genes, we conducted a PPI protein interaction analysis on 1046 differentially expressed genes. Finally, a network of Chinese medicine active molecule intersection genes was proposed, and the genes and their corresponding active molecules (Successful acid, Taraxerone, Taraxerol) were Macromolecular docking, respectively. The results showed that these four genes could be successfully docked with the responsive active molecules and had high binding affinity. In vivo, the low-dose treatment group of Sageretia theezans, the medium-dose treatment group of Sageretia theezans, and the high-dose treatment group of Bromelia can inhibit the proliferation of HUVECs cells. In vitro, the middle dose of Sageretia theezans has the best therapeutic effect on hemorrhoids, and the treatment of Sageretia theezans on hemorrhoids is correlated with the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E. CONCLUSION: To sum up, Sageretia theezans can alleviate the symptoms of hemorrhoids and is related to the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E.

microRNA-3037 targeting CYP6CY2 confers imidacloprid resistance to Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.

Maternal Hypermethylated Genes Contribute to Intrauterine Growth Retardation of Piglets in Rongchang Pigs.

The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.

Speckle-Tracking Echocardiography in Right Ventricular Function of Clinically Well Patients with Heart Transplantation.

Heart transplantation (HT) is the mainstream therapy for end-stage heart disease. However, the cardiac graft function can be affected by several factors. It is important to monitor HT patients for signs of graft dysfunction. Transthoracic echocardiography is a simple, first-line, and non-invasive method for the assessment of cardiac function. The emerging speckle-tracking echocardiography (STE) could quickly and easily provide additive information over traditional echocardiography. STE longitudinal deformation parameters are markers of early impairment of ventricular function. Although once called the "forgotten ventricle", right ventricular (RV) assessment has gained attention in recent years. This review highlights the potentially favorable role of STE in assessing RV systolic function in clinically well HT patients.

LECT2 mediates antibacterial immune response induced by Nocardia seriolae infection in the northern snakehead.

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84% identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish.

Multi-omics unveils tryptophan metabolic pathway as a key pathway influencing residual feed intake in Duroc swine.

The genetic trait of residual feed intake (RFI) holds considerable importance in the swine industry. Recent research indicates that the gut microbiota of pigs plays a pivotal role in the manifestation of the RFI trait. Nevertheless, the metabolic pathways involved in the functioning of these microorganisms remain elusive. Thus, based on the ranking of the RFI trait in Duroc pigs, the present study selected the top 10 and bottom 10 pigs as the experimental subjects. The distribution and metabolite differences of cecal microbiota were analyzed using 16S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. The low RFI cecal group was named LRC, and the high RFI cecal group was named HRC. The results indicate that the LRC group had lower RFI, feed conversion ratio (FCR), average daily feed intake (ADFI) (p < 0.001), and thinner backfat (p < 0.05) compared with the HRC group. We simultaneously recorded the foraging behavior as well, the LRC group had a significant increase in total time spent at the feeder per day (TPD) (p < 0.05) and a significant increase in average feed intake per mins (AFI) and the number of visits to the feeder per day (NVD) compared to the HRC group (p < 0.001). Clostridium_XVIII, Bulleidia, and Intestinimonas were significantly enriched in the LRC group (p < 0.01), while Sutterella, Fusobacterium, and Bacteroides were significantly increased in the HRC group (p < 0.01). In the metabolome, we detected 390 (248 metabolites up and 142 down in the LRC compared with HRC), and 200 (97 metabolites up and 103 down in the LRC compared with HRC) differential metabolites in positive and negative ionization modes. The comprehensive analysis found that in the LRC group, Escherichia and Eubacterium in the gut may increase serotonin content, respectively. Bacteroides may deplete serotonin. We suggest that the RFI may be partly achieved through tryptophan metabolism in gut microbes. In individuals with low RFI, gut microbes may enhance feed efficiency by enhancing host synthesis and metabolism of tryptophan-related metabolites.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.

Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.

Wnt/ß-catenin signaling inhibits oxidative stress-induced ferroptosis to improve interstitial cystitis/bladder pain syndrome by reducing NF-κB.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder syndrome of unknown etiology. Reactive oxygen species (ROS) plays a major role in ferroptosis and bladder dysfunction of IC/BPS, while the role of ferroptosis in IC/BPS progression is still unclear. This study aims to investigate the role and mechanism of ROS-induced ferroptosis in IC/BPS using cell and rat model. METHODS: We collected IC/BPS patient bladder tissue samples and established a LPS-induced IC/BPS rat model (LRM). The level of oxidative stress and ferroptosis in IC/BPS patients and LRM rats was analyzed. Function and regulatory mechanism of ferroptosis in IC/BPS were explored by in vitro and in vivo experiments. RESULTS: The patients with IC/BPS showed mast cells and inflammatory cells infiltration in bladder epithelial tissues. Expression of NRF2 was up-regulated, and GPX4 was decreased in IC/BPS patients compared with normal tissues. IC model cells underwent oxidative stress, which induced ferroptosis. These above results were validated in LRM rat models, and inhibition of ferroptosis ameliorated bladder dysfunction in LRM rats. Wnt/ß-catenin signaling was deactivated in IC/BPS patients and animals, and activation of Wnt/ß-catenin signaling reduced cellular free radical production, thereby inhibited ferroptosis in IC model cells. Mechanistically, the Wnt/ß-catenin signaling pathway inhibited oxidative stress-induced ferroptosis by down-regulating NF-κB, thus contributing to recover IC/BPS both in vitro and in vivo. CONCLUSIONS: We demonstrate for the first time that oxidative stress-induced ferroptosis plays an important role in the pathology of IC/BPS. Mechanistically, the Wnt/ß-catenin signaling suppressed oxidative stress-induced ferroptosis by down-regulating NF-κB to improve bladder injury in IC/BPS.

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Long-wavelength traveling waves of vasomotion modulate the perfusion of cortex.

Brain arterioles are active, multicellular complexes whose diameters oscillate at ∼ 0.1 Hz. We assess the physiological impact and spatiotemporal dynamics of vaso-oscillations in the awake mouse. First, vaso-oscillations in penetrating arterioles, which source blood from pial arterioles to the capillary bed, profoundly impact perfusion throughout neocortex. The modulation in flux during resting-state activity exceeds that of stimulus-induced activity. Second, the change in perfusion through arterioles relative to the change in their diameter is weak. This implies that the capillary bed dominates the hydrodynamic resistance of brain vasculature. Lastly, the phase of vaso-oscillations evolves slowly along arterioles, with a wavelength that exceeds the span of the cortical mantle and sufficient variability to establish functional cortical areas as parcels of uniform phase. The phase-gradient supports traveling waves in either direction along both pial and penetrating arterioles. This implies that waves along penetrating arterioles can mix, but not directionally transport, interstitial fluids.

A review of surgical and reconstructive techniques for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is an inflammatory follicular dermatological condition that typically affects the intertriginous and anogenital regions of the apocrine gland-bearing skin. The management of this chronic and recurring disease necessitates a combination of lifestyle changes, medication, and surgical approaches to achieve the best possible outcomes. While medical treatments are recommended for this multimodal disease, surgical therapy, which is the gold standard of treatment for HS, has proven to be the most effective treatment because it provides long-lasting local disease control, reduces the recurrence of lesions, and ensures complete healing of lesions. In the last decade, there has been exponential growth in research into various surgical techniques and reconstructive care, enabling patients to have more surgical options. There is a wide range of surgical management procedures available, such as incision and drainage, deroofing, excisional surgery, carbon dioxide laser therapy, and skin tissue-sparing excision with electrosurgical peeling. Among these surgical procedures, wide surgical excision is the best option since it can eradicate all the affected lesions. Meanwhile, the preferred approach to reconstruction at various anatomical locations remains debatable. Here, we review a variety of surgical treatments and reconstructive techniques for HS, particularly various flap techniques for the axillary, gluteal, and inframammary regions.