Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

A preliminary study of modified inflatable mediastinoscopic and single-incision plus one-port laparoscopic esophagectomy.

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

Biomimetic Design of 3D Fe3O4/V-EVOH Fiber-Based Self-Floating Composite Aerogel to Enhance Solar Steam Generation Performance.

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

Understanding nonuse of mandatory e-scooter helmets.

OBJECTIVES: Head injuries resulting from e-scooter use have led to calls for helmet use to be promoted or mandatory. Helmet use is mandatory for e-scooters in Australia but observational studies have reported significant levels of nonuse, particularly by riders of shared e-scooters. The aim of this study is to understand whether nonuse in the mandatory context is a consistent behavior for an individual or is situationally-influenced, and what are the factors associated with nonuse. METHODS: An online survey was completed between 2022 and 2023 by 360 adult e-scooter riders in Canberra, Australia. Riders were asked whether they had worn a helmet on their last ride and how often they had not worn a helmet when riding in the last 30 days. The survey also asked about rider characteristics (demographics, frequency of e-scooter and bicycle use, perceived risk of e-scooter use, e-scooter ownership, and risky behaviors while riding), trip duration and perceptions of the helmet requirement (knowledge of and support for the law). RESULTS: Respondents were mostly male, young, highly educated, and full-time workers. Of the 29.1% of riders who reported riding without a helmet in the last 30 days, 24.4% had worn a helmet at least once during that period and 4.8% had consistently not worn a helmet. Younger age, shared e-scooter use and more frequent riding frequency (shared e-scooters only) were associated with helmet nonuse in the bivariate analyses but not in the logistic regression. Logistic regression showed that the independent predictors of helmet nonuse were the number of risky riding behaviors, lack of knowledge, and lack of support for the law. CONCLUSIONS: Most nonuse of helmets in a mandatory context seems to be situational, rather than consistent. Many of the factors associated with nonuse of helmets for e-scooters are similar to those reported for bicycles. Nonuse of helmets appears to be one of a number of risky behaviors performed by riders, rather than being primarily an outcome that is specific to factors associated with helmets (e.g., concerns about hygiene, discomfort or availability).

In Situ Photogenerated Radicals of Hydroxyl Substituted Pyrene-Based Triphenylamines with Enhanced Transport and Free Doping/Post-Oxidation for Efficient Perovskite Solar Cells.

The high-performance hole transporting material (HTM) is one of the most important components for the perovskite solar cells (PSCs) in promoting power conversion efficiency (PCE). However, the low conductivity of HTMs and their additional requirements for doping and post-oxidation greatly limits the device performance. In this work, three novel pyrene-based derivatives containing methoxy-substituted triphenylamines units (PyTPA, PyTPA-OH and PyTPA-2OH) are designed and synthesized, where different numbers of hydroxyl groups are connected at the 2- or 2,7-positions of the pyrene core. These hydroxyl groups at the 2- or 2,7-positions of pyrene play a significantly role to enhance the intermolecular interactions that are able to generate in situ radicals with the assistance of visible light irradiation, resulting in enhanced hole transferring ability, as well as an enhanced conductivity and suppressed recombination. These pyrene-core based HTMs exhibit excellent performance in PSCs, which possess a higher PCE than those control devices using the traditional spiro-OMeTAD as the HTM. The best performance can be found in the devices with PyTPA-2OH. It has an average PCE of 23.44% (PCEmax = 23.50%), which is the highest PCE among the reported PSCs with the pyrene-core based HTMs up to date. This research offers a novel avenue to design a dopant-free HTM by the combination of the pyrene core, methoxy triphenylamines, and hydroxy groups.

Microstructural and Textural Evolution of Cold-Drawn Mg-Gd Wires during Annealing Treatment.

In addition to cold drawing, the process of annealing is also essential in the preparation of Mg-4.7 wt%Gd (G4.7) alloy wires. The effect of annealing treatment on the recrystallized microstructure and texture of cold-drawn G4.7 wires was investigated. The results demonstrate that the uniformity and regularity of the recrystallized grains, as well as the annealing texture, impact the follow-up cold drawing performance. When the as-drawn G4.7 wires were annealed at 375 °C, the recrystallized grains were refined, accompanied by uniformity and regularity. Accordingly, the G4.7 wire had a good subsequent drawing deformability, with a maximum accumulative true strain (ATS) of 144%. Additionally, the evolution of the microstructure was consistent with the evolution of the texture. While annealing at a lower temperature (325 °C), the {0002} basal texture of the G4.7 wire was weak, forming the main texture component <101¯0>//DD (the drawing direction). With the increase in temperature, the basal texture was gradually strengthened and the texture component transformed from <101¯0>//DD to a recrystallized texture based on <112¯0>//DD. Even under high-temperature annealing, the G4.7 wire was still affected by the cold-drawn deformation texture and could not fully recover to the as-extruded texture, thus causing a decrease in the subsequent drawing performance.

Exercise and osteoimmunology in bone remodeling.

Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-ß, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.

Deciphering dynamic interactions between spermatozoa and the ovarian microenvironment through integrated multi-omics approaches in viviparous Sebastes schlegelii.

The ovarian microenvironment plays a crucial role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding of this process in black rockfish (Sebastes schlegelii) using integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at the early spermatozoa-storage stage (1 month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Before fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promotes spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism that influences the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization.

Genotype and phenotype features and prognostic factors of neonatal-onset pyridoxine-dependent epilepsy: A systematic review.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a rare autosomal recessive disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase. This study aimed to systematically explore genotypic and phenotypic features and prognostic factors of neonatal-onset PDE. A literature search covering PubMed, Elsevier, and Web of Science was conducted from January 2006 to August 2023. We identified 56 eligible studies involving 169 patients and 334 alleles. The c.1279 G>C variant was the most common variant of neonatal-onset PDE (25.7 %). All patients were treated with pyridoxine; forty patients received dietary intervention therapy. 63.9 % of the patients were completely seizure-free; however, 68.6 % of the patients had neurodevelopmental delays. Additionally, homozygous c.1279 G>C variants were significantly associated with ventriculomegaly, abnormal white matter signal, and cysts (P<0.05). In contrast, homozygous c.1364 T>C was associated with clonic seizure (P=0.031). Pyridoxine used immediately at seizure onset was an independent protective factor for developmental delay (P=0.035; odds ratio [OR]: 3.14). Besides, pyridoxine used early in the neonatal period was a protective factor for language delay (P=0.044; OR: 4.59). In contrast, neonatal respiratory distress (P=0.001; OR: 127.44) and abnormal brain magnetic resonance imaging (P=0.049; OR: 3.64) were risk factors. Prenatal movement abnormality (P=0.041; OR: 20.56) and abnormal white matter signal (P=0.012; OR: 24.30) were risk factors for motor delay. Myoclonic seizure (P=0.023; OR: 7.13) and status epilepticus (P=0.000; OR: 9.93) were risk factors for breakthrough seizures. In conclusion, our study indicated that pyridoxine should be started immediately when unexplained neonatal seizures occur and not later than the neonatal period to prevent poor neurodevelopmental outcomes.

Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

MDSC-targeting gold nanoparticles enhance PD-1 tumor immunotherapy by inhibiting NLRP3 inflammasomes.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in the immune escape mechanisms that limit the efficacy of immunotherapeutic strategies. In the tumor microenvironment, NLRP3 inflammasome-driven Interleukin-1ß (IL-1ß) production serves to dampen antitumor immune responses, promoting tumor growth, progression, and immunosuppression. In this study, we revealed that gold nanoparticles (Au NPs) with a size of 30 nm disrupted NLRP3 inflammasome, but not other inflammasomes, in bone marrow-derived macrophages through abrogating NLRP3-NEK7 interactions mediated by reactive oxygen species (ROS). Density functional theory (DFT) calculations provided insights into the mechanism underlying the exceptional ROS scavenging capabilities of Au NPs. Additionally, when coupled with H6, a small peptide targeting MDSCs, Au NPs demonstrated the capacity to effectively reduce IL-1ß levels and diminish the MDSCs population in tumor microenvironment, leading to enhanced T cell activation and increased immunotherapeutic efficacy in mouse tumor models that are sensitive and resistant to PD-1 inhibition. Our findings unraveled a novel approach wherein peptide-modified Au NPs relieved the suppressive impact of the tumor microenvironment by inhibiting MDSCs-mediated IL-1ß release, which is the first time reported the employing a nanostrategy at modulating MDSCs to reverse the immunosuppressive microenvironment and may hold promise as a potential therapeutic agent for cancer immunotherapy.

Portable self-powered electrochemical aptasensing platform for ratiometric detection of mycotoxins based on multichannel photofuel cell.

Self-powered electrochemical sensors based on photofuel cells have attracted considerable research interest because their unique advantage of not requiring an external electric source, but their application in portable and multiplexed targets assay is limited by the inherent mechanism. In this work, a portable self-powered sensor constructed with multichannel photofuel cells was developed for the ratiometric detection of mycotoxins, namely ochratoxin A (OTA) and patulin (PAT). The spatially resolved CdS/Bi2S3-modified photoanodes and a shared Prussian Blue cathode were integrated on an etched indium-tin oxide slide to fabricate the multichannel photofuel cell. The aptamers of OTA and PAT were covalently bonded to individual photoanode regions to build sensitive interfaces, and the specific recognition of analytes impaired the output performance of constructed PFC. Accordingly, ratiometric sensing of OTA and PAT was achieved by utilizing the output performance of a control PFC as a reference signal. This approach effectively eliminates the impact of light intensity on the accuracy of the detection. Under the optimal conditions, the proposed sensing chip exhibited linear ranges of 2.0-1000 nM and 5.0-500 nM for OTA and PAT, respectively. The detection limits (3 S/N) were determined to be 0.25 nM for OTA and 0.27 nM for PAT. The developed ratiometric sensing method demonstrated good selectivity and stability in the simultaneous detection of OTA and PAT. It was successfully utilized for the analysis of OTA and PAT real samples. This work provides a new perspective for construction of portable and ratiometric self-powered sensing platform.

Ureteral reimplantation for the management of pelvic lipomatosis.

Introduction: Pelvic lipomatosis is a rare benign disease characterized by urethral elongation, bladder deformity, and/or hydronephrosis. Conservative management is not effective, and urinary diversion is the most effective treatment option but is usually unacceptable for relatively young patients. Ureteral reimplantation seemed to be an appropriate modality under these conditions. We present one case in which pelvic lipomatosis was managed with ureteral reimplantation. Patient presentation: A 45-year-old, previously healthy man presented with right flank pain. Pelvic CT and CT urography showed excessive pelvic fat, bilateral hydronephrosis, tortuous ureters, and a pear-shaped bladder, all of which indicated a diagnosis of pelvic lipomatosis. We performed laparoscopic bilateral urinary tract infection on this patient. At follow-up, bilateral hydronephrosis and flank pain were greatly relieved. Conclusion: Pelvic lipomatosis can be managed safely and effectively by urinary tract infection, but longer follow-up periods are needed to evaluate the long-term efficacy of this approach.

Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

Expression of concern: Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform.

Expression of concern for 'Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform' by Xunan Jing et al., Nanoscale, 2019, 11, 15508-15518, https://doi.org/10.1039/C9NR04768A.

Assessment of HMGB1 and NLRP3 in Determining Efficacy and Prognosis in Hemodialysis Patients with Chronic Renal Failure.

Background: In chronic renal failure (CRF), evaluating treatment efficacy and predicting prognosis is crucial. High Mobility Group Protein B1 (HMGB1) and Nod-like Receptor Protein 3 (NLRP3) were chosen as key markers in chronic renal failure to elucidate their roles in treatment response and prognosis, offering potential insights for enhancing patient care strategies. Objective: This study aims to analyze the clinical impact of HMGB1 and NLRP3 in patients with CRF undergoing hemodialysis. We investigated the relationship between HMGB1 and NLRP3 levels, the efficacy of hemodialysis treatment, and the prognosis for one-year survival. Methods: An observational study was conducted. The study included 62 CRF patients (Group A) admitted to our hospital from May 2020 to August 2022, and 40 healthy individuals undergoing routine medical check-ups during the same period (Group B). We compared the levels of HMGB1 and NLRP3 in the peripheral blood of Group A and Group B. Furthermore, we assessed changes in HMGB1 and NLRP3 before and after hemodialysis in CRF patients to evaluate treatment efficacy and prognostic indicators for one-year survival. Results: Group A exhibited significantly lower HMGB1 expression and higher NLRP3 expression compared to Group B. ROC curve analysis demonstrated that the areas under the curve (AUCs) for HMGB1 and NLRP3 in predicting effective hemodialysis for CRF were 0.884 (95% CI: 0.800-0.968) and 0.721 (95% CI: 0.594-0.848), respectively. The AUCs for HMGB1 and NLRP3 in predicting death from CRF were 0.885 (95% CI: 0.804-0.967) and 0.935 (95% CI: 0.875-0.995), respectively. Conclusions: Both HMGB1 and NLRP3 levels serve as valuable indicators for assessing the efficacy and prognosis of CRF patients undergoing hemodialysis.

Comparison of the Effects of Ureteroscopy with Holmium Laser Lithotripsy and Extracorporeal Shock Wave Lithotripsy in the Treatment of Ureteral Calculi.

Objective: This study aims to compare the efficacy of ureteroscopy with holmium laser lithotripsy and extracorporeal shock wave lithotripsy (ESWL) in treating ureteral calculus (UC). Methods: We enrolled 86 patients with UC treated in our urology department from November 2020 to November 2022. Group A (n=43) underwent ureteroscopic holmium laser lithotripsy, while Group B (n=43) received ESWL. We recorded treatment duration, post-treatment hematuria duration, and post-treatment stone clearance rates. Renal function and stress response were assessed before and 3 days after treatment. Post-treatment complications were documented, and patient quality of life was evaluated using the SF-36 health questionnaire. Results: Group A exhibited significantly shorter treatment and post-treatment hematuria durations compared to Group B (P < .05). In stones >1 cm, group A demonstrated a higher clearance rate (P < .05). Post-treatment, Group A showed improved renal function and lower stress response (P < .05). The incidence of post-treatment complications did not differ significantly between groups (P > .05), but SF-36 scores were higher in Group A (P < .05). Conclusions: Ureteroscopy with holmium laser lithotripsy proves effective in UC treatment, contributing to a shortened recovery period and enhanced patient quality of life.

Exploration of Diagnostic Deubiquitinating Enzymes in Endometriosis and Its Immune Infiltration.

The mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis. Calibration curves, ROC, DCA, and clinical impact curves verified the clinical usefulness of the nomogram model. In addition, the ssGSEA method was conducted to estimate 23 types of immune cells. A specific DUB gene signature was constructed with Lasso regression, univariate logistic regression, and SVM analysis. RT-qPCR validated the expression of biomarkers. A total of 85 endometriosis-related DUBs were identified in the eutopic endometrium. Among them, 20 DUBs were found to be correlated with the severity of endometriosis. A diagnostic risk model based on five DUB-related genes (USP21, USP48, ZRANB1, COPS5, and EIF3F) was developed using lasso-cox regression analysis. The nomogram model exhibited a strong predictive ability to diagnose endometriosis. KEGG analysis revealed that ubiquitin-mediated proteolysis was activated in patients suffering from severe symptoms. Analysis of immune cell infiltration revealed a positive correlation between USP21 and multiple immune cells in the eutopic endometrium. However, EIF3F showed an opposite relationship. Dysregulation of DUBs was related to the immune microenvironment in endometriosis. Results from RT-qPCR confirmed the expression of DEGs in clinical samples. In summary, the diagnostic model for endometriosis constructed using five differentially expressed DUB genes demonstrates strong diagnostic capability, suggesting that these genes could serve as potential candidate biomarkers and therapeutic targets.

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1ß, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.