Identification of macrophage-related genes in bladder cancer patients using single-cell sequencing and construction of a prognostic model.

Single-cell sequencing is an emerging technology that can effectively identify cell types in tumors. In the tumor microenvironment of bladder cancer, macrophages play a crucial role in invasion and immune escape. This study aimed to assess the expression of macrophage-related genes (MRGs) in the tumor microenvironment of bladder cancer patients and construct a prognostic model based on MRGs using bioinformatics methods. METHODS: Single-cell sequencing data from bladder cancer patients was downloaded from the GEO. After quality control and cell type identification, macrophages in the samples were extracted for re-clustering. Feature genes were then identified, and MRGs were assessed. Genetic data from TCGA database bladder cancer patients was also downloaded and organized. The intersection of MRGs and the TCGA gene set was determined. Clinical information was connected with this intersection, and the data was divided into training and validation sets. The training set was used for model construction and the validation set for model verification. A prognostic model based on MRGs was built using the LASSO algorithm and Cox regression. Patients were divided into high-risk and low-risk groups based on their prognostic features, and survival information in the training and validation sets was observed. The predictive ability of the model was assessed using a ROC curve, followed by a calibration plot to predict 1-, 3-, and 5-year survival rates. RESULTS: Four cell types were identified, and after extracting macrophages, three cell subgroups were clustered, resulting in 1,078 feature genes. The top 100 feature genes from each macrophage subgroup were extracted and intersected with TCGA expressed genes to construct the model. A risk prediction model composed of CD74, METRN, PTPRR, and CDC42EP5 was obtained. The survival and ROC curves showed that this model had good predictive ability. A calibration curve also demonstrated good prognostic ability for patients. CONCLUSION: This study, based on single-cell data, TCGA data, and clinical information, constructed an MRG-based prognostic model for bladder cancer using multi-omics methods. This model has good accuracy and reliability in predicting the survival and prognosis of patients with bladder cancer, providing a reference for understanding the interaction between MRGs and bladder cancer.

Effect of endoscopic sphincterotomy and endoscopic papillary balloon dilation endoscopic retrograde cholangiopancreatographies on the sphincter of Oddi.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP), with its clinical ad-vantages of less trauma and faster recovery, has become the primary treatment for choledocholithiasis. AIM: To investigate the effects of different ERCP procedures on the sphincter of Oddi. METHODS: The clinical data of 91 patients who underwent ERCP at Yixing Hospital of Traditional Chinese Medicine between February 2018 and February 2021 were analyzed retrospectively. The patients were divided into endoscopic sphincterotomy (EST, n = 24) and endoscopic papillary balloon dilation (EPBD, n = 67) groups. The duration of operation, pancreatic development, pancreatic sphincterotomy, intubation difficulties, stone recurrence, and incidence of reflux cholangitis and cholecystitis were statistically analyzed in patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction in the EST and EPBD groups. RESULTS: Differences in hypertension, diabetes, increased bilirubin, small diameter of the common bile duct, or ampullary diverticulum between the two groups were not significant. Statistically significant differences were observed between the two groups concerning sex and age (< 60 years). Patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction were higher in the EST group than in the EPBD group. The number of cases of pancreatic development, pancreatic duct sphincterotomy, and difficult intubation were higher in the EST group than in the EPBD group. The number of Oddi's sphincter manometries, ERCP surgical outcomes, and guidewires entering the pancreatic duct several times in EST group were lower than those in the EPBD group. The numbers of stone recurrences, reflux cholangitis, and cholecystitis were higher in the EST group than in the EPBD group. CONCLUSION: In summary, common bile duct stones, pancreatitis history, and multiple guided wire introductions into the pancreatic duct are independent risk factors for EST and EPBD. Based on this evidence, this study can provide actionable insights for clinicians and researchers.

Selective active resonance tuning for multi-mode nonlinear photonic cavities.

Resonant enhancement of nonlinear photonic processes is critical for the scalability of applications such as long-distance entanglement generation. To implement nonlinear resonant enhancement, multiple resonator modes must be individually tuned onto a precise set of process wavelengths, which requires multiple linearly-independent tuning methods. Using coupled auxiliary resonators to indirectly tune modes in a multi-resonant nonlinear cavity is particularly attractive because it allows the extension of a single physical tuning mechanism, such as thermal tuning, to provide the required independent controls. Here we model and simulate the performance and tradeoffs of a coupled-resonator tuning scheme which uses auxiliary resonators to tune specific modes of a multi-resonant nonlinear process. Our analysis determines the tuning bandwidth for steady-state mode field intensity can significantly exceed the inter-cavity coupling rate g if the total quality factor of the auxiliary resonator is higher than the multi-mode main resonator. Consequently, over-coupling a nonlinear resonator mode to improve the maximum efficiency of a frequency conversion process will simultaneously expand the auxiliary resonator tuning bandwidth for that mode, indicating a natural compatibility with this tuning scheme. We apply the model to an existing small-diameter triply-resonant ring resonator design and find that a tuning bandwidth of 136 GHz ≈ 1.1 nm can be attained for a mode in the telecom band while limiting excess scattering losses to a quality factor of 106. Such range would span the distribution of inhomogeneously broadened quantum emitter ensembles as well as resonator fabrication variations, indicating the potential for the auxiliary resonators to enable not only low-loss telecom conversion but also the generation of indistinguishable photons in a quantum network.

Characteristics of painful temporomandibular disorders and their influence on jaw functional limitation and oral health-related quality of life.

BACKGROUND: There is limited knowledge about the impact of painful temporomandibular disorders (TMDs) and pain characteristics on jaw functional limitation and oral health-related quality of life (OHRQoL) in TMD patients. OBJECTIVES: The influence of painful TMDs and pain characteristics on jaw functional limitation and OHRQoL was investigated. Inter-relationships between limitation in jaw function and various OHRQoL domains, along with facial pain attributes predicting impaired jaw function and diminished OHRQoL were also examined. METHODS: TMD patients were recruited from a university-based hospital. A comprehensive questionnaire comprising demographic variables, the DC/TMD Symptom Questionnaire, Graded Chronic Pain Scale, Jaw Functional Limitation Scale-8 (JFLS-8) and Oral Health Impact Profile-TMD (OHIP-TMD) was administered. Participants underwent a protocolized physical examination, and TMD diagnoses were determined utilising the DC/TMD algorithms. Participants were subsequently stratified into intra-articular/pain-related/combined TMD groups, as well as no TMD pain, acute/chronic pain and low/high-intensity pain groups. Data were assessed using non-parametric and hierarchical linear regression analyses (α = .05). RESULTS: The final sample consisted of 280 participants (mean age 31.2 (SD 11.8) years; 79.3% women). Significant differences in pain characteristics, JFLS-8, and global OHIP scores were observed across the various TMD subtypes, pain chronicity and pain intensity categories. Pain intensity and pain-related interference exhibited moderate correlations with JFLS-8 and global OHIP scores (rs = 0.53-0.60). Moderate associations were also noted between JFLS-8 and global OHIP, as well as most OHIP domains (rs = 0.42-0.64). Both jaw functional limitation and OHRQoL were predicted by sex, pain intensity and pain-related interference. CONCLUSIONS: Sex, pain intensity and pain-related interference are key determinants for both impaired jaw function and diminished OHRQoL, with pain-related interference exerting a more pronounced effect.

3-chloro-1,2-propanediol induces oxidative stress and promotes testicular damage and infertility in rats through CYP2C9.

3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.

BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo.

BACKGROUND: Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored. METHODS: The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts' tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate's efflux were analyzed through the vanadate-sensitive ATPase assay, [125I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence. RESULTS: We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What's more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity. CONCLUSIONS: This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers.

MiR-17∼92 is involved in NF-κB activation via targeting the ubiquitin-editing proteins to mediate RIP1 complex polyubiquitinations in ABC-DLBCL.

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor. Importantly, miR-17∼92 promoted NF-κB activation through directly targeting multiple ubiquitin-editing regulators to lead to increase the K63-linked polyubiquitination and decrease the K48-linked polyubiquitination of RIP1 complex in ABC-DLBCL. We further found that miR-17∼92 selectively activated IκB-α and NF-κB p65 but not NF-κB p52/p100, and high miR-17∼92 expression was also associated with poorer outcome in ABC-DLBCL patients. Overall, our results showed that miR-17∼92 selectively activated the canonical NF-κB signaling via targeting ubiquitin-editing regulators to lead to constitutively NF-κB activation and poorer outcome in ABC-DLBCL. These findings uncovered an innovative function of miR-17∼92 and previously unappreciated regulatory mechanism of NF-κB activation in ABC-DLBCL. Targeting miR-17∼92 may thus provide a novel bio-therapeutic strategy for ABC-DLBCL patients.

Is Upper Extremity or Lower Extremity Function More Important for Patient Satisfaction? An Analysis of 24-Month Outcomes from the QOD Cervical Spondylotic Myelopathy Cohort.

STUDY DESIGN: Retrospective analysis of a prospective, multicenter registry. OBJECTIVE: To assess whether upper or lower limb mJOA improvement more strongly associates with patient satisfaction after surgery for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: The modified Japanese Orthopaedic Association (mJOA) is commonly used to assess functional status in patients with CSM. Patients present with upper and/or lower extremity dysfunction, and it is unclear whether improvement in one and/or both symptoms drives postoperative patient satisfaction. METHODS: This study utilizes the prospective Quality Outcomes Database (QOD) CSM data set. Clinical outcomes included mJOA and North American Spine Society (NASS) satisfaction. The upper limb mJOA score was defined as upper motor plus sensory mJOA, and the lower limb mJOA as lower motor plus sensory mJOA. Ordered logistic regression was used to determine whether upper or lower limb mJOA was more closely associated with NASS satisfaction, adjusting for other covariates. RESULTS: Overall, 1141 patients were enrolled in the QOD CSM cohort. In all, 780 had both preoperative and 24-month mJOA scores, met inclusion criteria, and were included for analysis. The baseline mJOA was 12.1±2.7, and postoperatively, 85.6% would undergo surgery again (NASS 1 or 2, satisfied). Patients exhibited mean improvement in both upper (baseline:3.9±1.4 vs. 24 mo:5.0±1.1, P<0.001) and lower limb mJOA (baseline:3.9±1.4 vs. 24 mon:4.5±1.5, P<0.001); however, the 24-month change in the upper limb mJOA was greater (upper:1.1±1.6 vs. lower:0.6±1.6, P<0.001). Across 24-month NASS satisfaction, the baseline upper and lower limb mJOA scores were similar (pupper=0.28, plower=0.092). However, as satisfaction decreased, the 24-month change in upper and lower limb mJOA decreased as well (pupper<0.001, plower<0.001). Patients with NASS scores of 4 (lowest satisfaction) did not demonstrate significant differences from baseline in upper or lower limb mJOA (P>0.05). In ordered logistic regression, NASS satisfaction was independently associated with upper limb mJOA improvement (OR=0.81; 95% CI: 0.68-0.97; P=0.019) but not lower limb mJOA improvement (OR=0.84; 95% CI: 0.70-1.0; P=0.054). CONCLUSIONS: As the magnitude of upper and lower mJOA improvement decreased postoperatively, so too did patient satisfaction with surgical intervention. Upper limb mJOA improvement was a significant independent predictor of patient satisfaction, whereas lower limb mJOA improvement was not. These findings may aid preoperative counseling, stratified by patients' upper and lower extremity treatment expectations. LEVEL OF EVIDENCE: Level-III.

Impact of educational background on preoperative disease severity and postoperative outcomes among patients with lumbar spondylolisthesis: a Quality Outcomes Database study.

OBJECTIVE: Deficiency in patient education has been correlated with increased disease-related morbidity and decreased access to care. However, the associations between educational level, preoperative disease severity, and postoperative outcomes in patients with lumbar spondylolisthesis have yet to be explored. METHODS: The spondylolisthesis dataset of the Quality Outcomes Database (QOD)-a cohort with prospectively collected data by the SpineCORe study team of the 12 highest enrolling sites with an 81% follow-up at 5 years -was utilized and stratified for educational level. Patients were classified into three categories (high school or less, graduate, or postgraduate). Patient-reported outcome measures (PROMs) documented at baseline and follow-up included Oswestry Disability Index (ODI) score, EQ-5D in quality-adjusted life years, and numeric rating scale (NRS) scores for back and leg pain. Disease severity was measured with PROMs. Postoperatively, patients also completed the North American Spine Society assessment to measure their satisfaction with surgery. Multivariable regression analysis was used to compare education level with disease severity and postoperative outcomes. RESULTS: A total of 608 patients underwent analysis, with 260 individuals (42.8%) at an educational level of high school or less. On univariate analysis, baseline disease severity was worse among patients with lower levels of education. On multivariable regression analysis, patients with postgraduate level of education had significantly lower ODI scores (ß = -3.75, 95% CI -7.31 to -0.2, p = 0.039) compared to graduates, while the other PROMs were not associated with significant differences at baseline. Five years postoperatively, patients from various educational backgrounds exhibited similar rates of minimal clinically important differences in PROMs. Nevertheless, patients with the lowest educational level had higher ODI scores (27.1, p < 0.01), lower EQ-5D scores (0.701, p < 0.01), and higher NRS leg pain (3.0, p < 0.01) and back pain (4.0, p < 0.01) scores compared to those with graduate or postgraduate levels of education. The odds for postoperative satisfaction were also comparable between cohorts at 5 years (reference, graduate level; high school or less, OR 0.87, 95% CI 0.46-1.64, p = 0.659; postgraduate, OR 1.6, 95% CI 0.7-3.65, p = 0.262). CONCLUSIONS: Lower patient education level was associated with a greater baseline disease severity in patients with lumbar spondylolisthesis. Surgery demonstrated similar benefits irrespective of educational background; however, individuals with lower educational level reported lower outcomes overall. This emphasizes the need for enhanced health literacy to mitigate disparities for reported outcomes.

Motive and Opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements-an LLMPP study.

Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit": HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of, and mechanisms driving, IG vs non-IG MYC rearrangements have not been elucidated. Here we used custom targeted capture and/or whole genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, while BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because one IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

Staged Versus Same-Day Surgery in Circumferential Minimally Invasive Deformity Correction.

BACKGROUND AND OBJECTIVES: We sought to compare long-term clinical and radiographic outcomes in patients who underwent staged vs same-day circumferential minimally invasive surgery (cMIS) for adult spinal deformity (ASD). METHODS: We reviewed staged and same-day cMIS ASD cases in a prospective multi-institution database to compare preoperative and 2-year clinical and radiographic parameters between cohorts. RESULTS: A total of 85 patients with a 2-year follow-up were identified (27 staged, 58 same-day). Staged patients had more extensive surgeries and greater hospital length of stay (all P < .001). There were no significant differences in preoperative or 2-year postoperative clinical metrics between cohorts. Patients in the staged cohort also had greater preoperative coronal deformity and thus experienced greater reduction in coronal deformity at 2 years (all P < .01). CONCLUSION: Patients undergoing staged or same-day cMIS correction had similar outcomes at 2 years postoperatively. Staged cMIS ASD correction may be more appropriate in patients with greater deformity, higher frailty, and who require longer, more extensive surgeries.

Comparison of ultrasound guidance with landmark guidance for symptomatic benefits in knee, hip and hand osteoarthritis: Systematic review and meta-analysis of randomised controlled trials.

Introduction: More than half of the patients with moderate and severe osteoarthritis (OA) report unsatisfactory pain relief, requiring consideration of intra-articular (IA) injections as the second-line management. Ultrasound-guided IA injection has proven evidence of higher accuracy in administering IA injectates into the joints than landmark-guided or blind IA injections. However, questions remain about translating higher accuracy rates of ultrasound-guided injection into better clinical improvements. Therefore, we examined the symptomatic benefits (pain, function and patient satisfaction) of ultrasound-guided injection in knee, hip and hand OA compared with blind injections by synthesising a systematic review and meta-analysis of randomised controlled trials (RCT). Methods: PubMed, Medline and Embase databases were searched for eligible studies from their inception to August 28, 2023. Results: Out of 295 records, our meta-analysis included four RCTs (338 patients with knee OA), demonstrating significant improvement in procedural pain [-0.89 (95% CI -1.25, -0.53)], pain at follow-up [-0.51 (95% CI -0.98, -0.04)] and function [1.30 (95% CI 0.86, 1.73)], favouring ultrasound guidance. One single study showed higher patient satisfaction with ultrasound guidance. Conclusion: Ultrasound-guided IA injection provided superior clinical outcomes compared with landmark-guided IA injection.

Ultra-High Proportion of Grain Boundaries in Zinc Metal Anode Spontaneously Inhibiting Dendrites Growth.

Aqueous Zn-ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries. Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra-high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface. The ultra-high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15 µm Fs-Zn||MnO2 pouch cell achieves an energy density of 249.4 Wh kg-1 and operates for over 60 cycles at a depth-of-discharge of 23 %. The recognition of the favorable influence exerted by UP-GBs paves a new way for other metal batteries.

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis.

Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45+ CTCs) that resisted T cell attack. A higher percentage of CD45+ CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45+ tumor cells orchestrated an immunosuppressive milieu and CD45+ CTCs exhibited remarkably stronger metastatic potential than CD45- CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

RNA Interference-Mediated Suppression of Ecdysone Signaling Inhibits Choriogenesis in Two Coleoptera Species.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the effect of chemical components on eggshell deserve further exploration. In two representative coleopterans, a coccinellid Henosepilachna vigintioctopunctata and a chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and reduced CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two coleopteran species. Moreover, our findings suggest the deposition of a CLS on the chorions.

Drp1 controls complex II assembly and skeletal muscle metabolism by Sdhaf2 action on mitochondria.

The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.

Thoracoscopic resection of paraesophageal ectopic mediastinal parathyroid adenoma in the superior posterior mediastinum: a case report.

BACKGROUND: The ectopic superior parathyroid in the tracheoesophageal groove and paraesophageal region is rare. Hyperparathyroidism results when these glands become hyperfunctioning. That may necessitate surgical intervention in the form of parathyroidectomy, which requires a transsternal or transthoracic approach due to a deeply seated mediastinal parathyroid gland. Minimally invasive strategies have emerged recently as an alternative approach with less morbidity. CASE PRESENTATION: We present a case of the paraesophageal ectopic parathyroid gland in the superior posterior mediastinum, which was successfully treated with thoracoscopic resection. CONCLUSION: The current imaging tools improve the thoracoscopic management of mediastinal parathyroid glands. Video-assisted thoracoscopic surgery (VATS) can provide access and exposure to ectopic parathyroid adenoma with low morbidity and financial burden.

Comparing posterior cervical foraminotomy with anterior cervical discectomy and fusion in radiculopathic patients: an analysis from the Quality Outcomes Database.

OBJECTIVE: The objective of this study was to compare clinical and patient-reported outcomes (PROs) between posterior foraminotomy and anterior cervical discectomy and fusion (ACDF) in patients presenting with cervical radiculopathy. METHODS: The Quality Outcomes Database was queried for patients who had undergone ACDF or posterior foraminotomy for radiculopathy. To create two highly homogeneous groups, optimal individual matching was performed at a 5:1 ratio between the two groups on 29 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, underlying pathologies, and levels treated). Outcomes of interest were length of stay, reoperations, patient-reported satisfaction, increase in EQ-5D score, and decrease in Neck Disability Index (NDI) scores for arm and neck pain as long as 1 year after surgery. Noninferiority analysis of achieving patient satisfaction and minimal clinically important difference (MCID) in PROs was performed with an accepted risk difference of 5%. RESULTS: A total of 7805 eligible patients were identified: 216 of these underwent posterior foraminotomy and were matched to 1080 patients who underwent ACDF. The patients who underwent ACDF had more underlying pathologies, lower EQ-5D scores, and higher NDI and neck pain scores at baseline. Posterior foraminotomy was associated with shorter hospitalization (0.5 vs 0.9 days, p < 0.001). Reoperations within 12 months were significantly more common among the posterior foraminotomy group (4.2% vs 1.9%, p = 0.04). The two groups performed similarly in PROs, with posterior foraminotomy being noninferior to ACDF in achieving MCID in EQ-5D and neck pain scores but also having lower rates of maximal satisfaction at 12 months (North American Spine Society score of 1 achieved by 65.2% posterior foraminotomy patients vs 74.6% of ACDF patients, p = 0.02). CONCLUSIONS: The two procedures were found to be offered to different populations, with ACDF being selected for patients with more complicated pathologies and symptoms. After individual matching, posterior foraminotomy was associated with a higher reoperation risk within 1 year after surgery compared to ACDF (4.2% vs 1.9%). In terms of 12-month PROs, posterior foraminotomy was noninferior to ACDF in improving quality of life and neck pain. The two procedures also performed similarly in improving NDI scores and arm pain, but ACDF patients had higher maximal satisfaction rates.

Crucial roles of specialized chitinases in elytral and hindwing cuticles construction in Leptinotarsa decemlineata.

BACKGROUND: The Colorado potato beetle (CPB), Leptinotarsa decemlineata, is a major potato (Solanum tuberosum) pest, infesting over 16 million km2 and causing substantial economic losses. The insect cuticle forms an apical extracellular matrix (ECM) envelope covering exposed organs to direct morphogenesis and confer structural protection. While select chitinase (Cht) genes have proven essential for larval development, their potential activities directing ECM remodeling underlying adult wing maturation remain undefined. RESULTS: We investigated the expression patterns and performed an oral RNA interference (RNAi) screen targeting 19 LdChts in late-instar L. decemlineata larvae. Subsequently, we assessed their effects on adult eclosion and wing characteristics. Knockdown of LdCht5, LdCht7, LdCht10, LdIDGF2, and LdIDGF4, as well as others from Group IV (LdCht15, LdCht12, LdCht17, and LdCht13) and Groups VII-X (LdCht2, LdCht11, LdCht1, and LdCht3), resulting in shrunken, misshapen elytra with reduced areal density, as well as transverse wrinkling and impaired wing-tip folding in hindwings. Scanning electron micrographs revealed eroded elytral ridges alongside thinned, ruptured hindwing veins, indicative of mechanical fragility post-LdCht suppression. Spectroscopic analysis uncovered biomolecular alterations underlying the elytral anomalies, including decreases in peaks representing chitin, proteins, and lipids. This loss of essential ECM components provides evidence for the fragility, wrinkling, and shrinkage observed in the RNAi groups. CONCLUSION: Our findings elucidate the crucial role of chitinases in the turnover of chitinous cuticles on beetle wings, offering insights into RNAi-based control strategies against this invasive pest. © 2024 Society of Chemical Industry.

Small-molecule agents for cancer immunotherapy.

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.