In Vivo Evaluation of 68Ga-Labeled NOTA-EGFRvIII Aptamer in EGFRvIII-Positive Glioblastoma Xenografted Model.

EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the 68Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET). EGFRvIII aptamer was selected using the SELEX technology, and flow cytometry and fluorescence microscopy verified the high binding affinity to EGFRvIII positive U87MG vIII 4.12 glioma cells but not to EGFRvIII negative U87MG cells. The EGFRvIII aptamer was conjugated with a chelator (1,4,7-triazanonane-1,4,7-triyl)triacetic acid (NOTA) for 68Ga-labeling. The 68Ga-NOTA-EGFRvIII aptamer was prepared using the preconcentration-based labeling method with a high radiolabeling yield at room temperature. Ex vivo biodistribution analyses confirmed the significantly higher tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in EGFRvIII-expressing xenograft tumors than that in EGFRvIII negative tumors, confirming the specific tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in vivo. PET imaging studies revealed a high retention rate of the 68Ga-NOTA-EGFRvIII aptamer in U87MG vIII 4.12 tumors but only low uptake levels in U87-MG tumors, suggesting that the 68Ga-NOTA-EGFRvIII aptamer may be used as a PET imaging agent for EGFRvIII-expressing glioblastoma.

Comparison emergence of sedation, using dexmedetomidine and remimazolam, in spinal anaesthesia - double blinded randomized controlled trial.

Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.

The effect of preoperative botulinum toxin a injection on traction force during hernia repair: a prospective, single-blind study, intra-patient comparison using contralateral side as a control.

PURPOSE: Ventral hernias are a common complication of laparotomy, posing challenges particularly when primary fascial closure is unattainable. Although chemical component separation using preoperative botulinum toxin A (BTX) injections has emerged as a promising adjunct, objective evidence of its efficacy remains limited. This study aimed to objectively assess the effect of preoperative BTX on traction force during ventral hernia repair. METHODS: A prospective, single-blind study was conducted on patients with midline incisional hernias following liver transplantation. BTX was administered unilaterally, and the traction force required to medially advance the anterior rectus sheath was measured intraoperatively. Pre- and post-injection CT scans were analyzed for changes in hernia size and LAW muscle measurements. Statistical analyses were performed to evaluate traction force differences between BTX-injected and uninjected sides. RESULTS: Ten patients underwent hernia repair with primary fascial closure achieved in all cases. Comparison of pre- and post-injection CT scans showed no significant changes in hernia size. LAW muscle length increased by 1.8 cm, while thickness decreased by 0.2 cm. Intraoperative traction force measurements revealed a significant reduction on the BTX-injected side compared to the uninjected side (p < 0.0001). The traction force ratio on the BTX-injected to the uninjected side averaged 57%, indicating the efficacy of BTX in reducing tension. CONCLUSION: Preoperative BTX significantly reduces traction force during ventral hernia repair, highlighting its potential as an adjunctive therapy in complex cases. While challenges remain in patient selection and outcome assessment, BTX offers a promising avenue for enhancing abdominal wall reconstruction outcomes and reducing surgical complications.

Polyhexamethylene guanidine phosphate induces pyroptosis via reactive oxygen species-regulated mitochondrial dysfunction in bronchial epithelial cells.

Pyroptosis is a form of programmed cell death characterized by gasdermin (GSDM)-mediated pore formation in the cell membrane, resulting in the release of pro-inflammatory cytokines and cellular lysis. Increasing evidence has shown that pyroptosis is responsible for the progression of various pulmonary disorders. The inhalation of polyhexamethylene guanidine (PHMG) causes severe lung inflammation and pulmonary toxicity; however, the underlying mechanisms are unknown. Therefore, in this study, we investigate the role of pyroptosis in PHMG-induced pulmonary toxicity. We exposed bronchial epithelial cells, BEAS-2B, to PHMG phosphate (PHMG-p) and evaluated cell death type, reactive oxygen species (ROS) levels, and relative expression levels of pyroptosis-related proteins. Our data revealed that PHMG-p reduced viability and induced morphological alterations in BEAS-2B cells. Exposure to PHMG-p induced excessive accumulation of mitochondrial ROS (mtROS) in BEAS-2B cells. PHMG-p activated caspase-dependent apoptosis as well as NLRP3/caspase-1/GSDMD-mediated- and caspase-3/GSDME-mediated pyroptosis through mitochondrial oxidative stress in BEAS-2B cells. Notably, PHMG-p reduced mitochondrial respiratory function and induced the translocation of Bax and cleaved GSDM into the mitochondria, leading to mitochondrial dysfunction. Our results enhanced our understanding of PHMG-p-induced lung toxicity by demonstrating that PHMG-p induces pyroptosis via mtROS-induced mitochondrial dysfunction in bronchial epithelial cells.

Machine learning model based on radiomics features for AO/OTA classification of pelvic fractures on pelvic radiographs.

Depending on the degree of fracture, pelvic fracture can be accompanied by vascular damage, and in severe cases, it may progress to hemorrhagic shock. Pelvic radiography can quickly diagnose pelvic fractures, and the Association for Osteosynthesis Foundation and Orthopedic Trauma Association (AO/OTA) classification system is useful for evaluating pelvic fracture instability. This study aimed to develop a radiomics-based machine-learning algorithm to quickly diagnose fractures on pelvic X-ray and classify their instability. data used were pelvic anteroposterior radiographs of 990 adults over 18 years of age diagnosed with pelvic fractures, and 200 normal subjects. A total of 93 features were extracted based on radiomics:18 first-order, 24 GLCM, 16 GLRLM, 16 GLSZM, 5 NGTDM, and 14 GLDM features. To improve the performance of machine learning, the feature selection methods RFE, SFS, LASSO, and Ridge were used, and the machine learning models used LR, SVM, RF, XGB, MLP, KNN, and LGBM. Performance measurement was evaluated by area under the curve (AUC) by analyzing the receiver operating characteristic curve. The machine learning model was trained based on the selected features using four feature-selection methods. When the RFE feature selection method was used, the average AUC was higher than that of the other methods. Among them, the combination with the machine learning model SVM showed the best performance, with an average AUC of 0.75±0.06. By obtaining a feature-importance graph for the combination of RFE and SVM, it is possible to identify features with high importance. The AO/OTA classification of normal pelvic rings and pelvic fractures on pelvic AP radiographs using a radiomics-based machine learning model showed the highest AUC when using the SVM classification combination. Further research on the radiomic features of each part of the pelvic bone constituting the pelvic ring is needed.

Deep-learning-based pelvic automatic segmentation in pelvic fractures.

With the recent increase in traffic accidents, pelvic fractures are increasing, second only to skull fractures, in terms of mortality and risk of complications. Research is actively being conducted on the treatment of intra-abdominal bleeding, the primary cause of death related to pelvic fractures. Considerable preliminary research has also been performed on segmenting tumors and organs. However, studies on clinically useful algorithms for bone and pelvic segmentation, based on developed models, are limited. In this study, we explored the potential of deep-learning models presented in previous studies to accurately segment pelvic regions in X-ray images. Data were collected from X-ray images of 940 patients aged 18 or older at Gachon University Gil Hospital from January 2015 to December 2022. To segment the pelvis, Attention U-Net, Swin U-Net, and U-Net were trained, thereby comparing and analyzing the results using five-fold cross-validation. The Swin U-Net model displayed relatively high performance compared to Attention U-Net and U-Net models, achieving an average sensitivity, specificity, accuracy, and dice similarity coefficient of 96.77%, of 98.50%, 98.03%, and 96.32%, respectively.

Selective Enhancement of Viewing Angle Characteristics and Light Extraction Efficiency of Blue Thermally Activated Delayed Fluorescence Organic Light-Emitting Diodes through an Easily Tailorable Si3N4 Nanofiber Structure.

We selectively improved the viewing angle characteristics and light extraction efficiency of blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) by tailoring a nanofiber-shaped Si3N4 layer, which was used as an internal scattering layer. The diameter of the polymer nanofibers changed according to the mass ratio of polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) in the polymer solution for electrospinning. The Si3N4 nanofiber (SNF) structure was fabricated by etching an Si3N4 film using the PAN/PMMA nanofiber as a mask, making it easier to adjust parameters, such as the diameter, open ratio, and height, even though the SNF structure was randomly shaped. The SNF structures exhibited lower transmittance and higher haze with increasing diameter, showing little correlation with their height. However, all the structures demonstrated a total transmittance of over 80%. Finally, by applying the SNF structures to the blue TADF OLEDs, the external quantum efficiency was increased by 15.6%. In addition, the current and power efficiencies were enhanced by 23.0% and 25.6%, respectively. The internal light-extracting SNF structure also exhibited a synergistic effect with the external light-extracting structure. Furthermore, when the viewing angle changed from 0° to 60°, the peak wavelength and CIE coordinate shift decreased from 20 to 6 nm and from 0.0561 to 0.0243, respectively. These trends were explained by the application of Snell's law to the light path and were ultimately validated through finite-difference time-domain simulations.

Molecular characterization and antibiotic resistance of Staphylococcus aureus strains isolated from patients with diarrhea in Korea between the years 2007 and 2022.

To investigate the molecular characteristics and antibiotic resistance of Staphylococcus aureus isolates from patients with diarrhea in Korea, 327 S. aureus strains were collected between 2007 and 2022. The presence of staphylococcal enterotoxin (SE) and toxic shock syndrome toxin-1 (TSST-1) genes in S. aureus isolates was determined by PCR. The highest expression of the TSST-1 gene was found in the GIMNO type (43.1% of GIMNO type). GIMNO type (Type I) refers to each staphylococcal enterotoxin (SE) gene gene (initials of genes): G = seg; I = sei; M = selm; N = seln; O = selo. Moreover, Type I isolates showed a significantly higher resistance to most antibiotics. A total of 195 GIMNO-type S. aureus strains were analyzed using multilocus sequence typing (MLST), and 18 unique sequence types (STs) were identified. The most frequent sequence type was ST72 (36.9%), followed by ST5 (22.1%) and ST30 (16.9%). Interestingly, ST72 strains showed a higher prevalence of MRSA than the other STs. In conclusion, our results were the first reported for S. aureus strains in Korea, which significantly expanded S. aureus genotype information for the surveillance of pathogenic S. aureus and may provide important epidemiological information to resolve several infectious diseases caused by S. aureus. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01478-9.

SAN: Mitigating spatial covariance heterogeneity in cortical thickness data collected from multiple scanners or sites.

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called spatial autocorrelation normalization (SAN) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package.

Evaluating Pain Management from Peripheral Nerve Block for Geriatric Patients following Bipolar Hemiarthroplasty for Displaced Femoral-Neck Fracture.

INTRODUCTION: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness in postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). METHODS: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: the patient-controlled analgesia (PCA) group (n = 132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n = 99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 h postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin, length of hospital stay, and total morphine usage after surgery. RESULTS: Postoperative resting VAS at 6 h and 48 h was significantly lower in the PNB+PCA group compared with the PCA group (p = 0.075, p = 0.0318, respectively). However, there was no significant difference in either resting VAS at 24 h or active VAS. Complications of pneumonia and delirium until 1 month postoperative were significantly lower in the PNB + PCA group than the PCA group (p = 0.0022, p = 0.0055, respectively). CONCLUSION: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

Human ST3Gal II and ST6GalNAc IV genes increase human serum-mediated cytotoxicity to xenogeneic cells.

Carbohydrate-antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self-defense and immunity. Xeno-reactive antibodies included in natural human sera play a protecting role in an acute phase-rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation-pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV-transfected PK15 cells, as compared to the control. In the hST6Gal I-carrying cells, the cytotoxicity to human serum was rather decreased. Moreover, flow cytometry analysis revealed that an alteration of pig glycosylation-pattern by hST3Gal II or hST6GalNAc IV influences on a binding of human IgM or IgG, respectively, in pig kidney cells, regardless of Gal antigen alteration. Finally, we found that hST6GalNAc IV contributed to increase of terminal disialylated tetrasaccharide structure, disialyl T antigen, as evidenced by increase of the MAL II lectin binding capacity in the hST6GalNAc IV-transfected PK15 cells, compared with control. Therefore, our results suggest that carbohydrate antigens, such as disialyl T antigen, newly synthesized by the ST3Gal II- and ST6GalNAc IV are potentially believed to be new xeno-reactive elements.

Hollow Microcavity Electrode for Enhancing Light Extraction.

Luminous efficiency is a pivotal factor for assessing the performance of optoelectronic devices, wherein light loss caused by diverse factors is harvested and converted into the radiative mode. In this study, we demonstrate a nanoscale vacuum photonic crystal layer (nVPCL) for light extraction enhancement. A corrugated semi-transparent electrode incorporating a periodic hollow-structure array was designed through a simulation that utilizes finite-difference time-domain computational analysis. The corrugated profile, stemming from the periodic hollow structure, was fabricated using laser interference lithography, which allows the precise engineering of various geometrical parameters by controlling the process conditions. The semi-transparent electrode consisted of a 15 nm thick Ag film, which acted as the exit mirror and induced microcavity resonance. When applied to a conventional green organic light-emitting diode (OLED) structure, the optimized nVPCL-integrated device demonstrated a 21.5% enhancement in external quantum efficiency compared to the reference device. Further, the full width at half maximum exhibited a 27.5% reduction compared to that of the reference device, demonstrating improved color purity. This study presents a novel approach by applying a hybrid thin film electrode design to optoelectronic devices to enhance optical efficiency and color purity.

Comparison of effects of telmisartan versus valsartan on post-induction hypotension during noncardiac surgery: a prospective observational study.

BACKGROUND: Telmisartan is considered more potent than valsartan. Hemodynamic response during anesthesia induction may be influenced by anti-hypertension (HTN) medication. The present study compared the effect of anti-HTN medications on post-induction hypotension during noncardiac surgeries. METHODS: This observational study standardized the anesthetic regimen across patients, with hypotension defined as mean blood pressure (BP) of less than 65 mmHg. The hemodynamic changes within 5 min before and after endotracheal intubation, and within 10 min before and after surgical incision were measured. Transthoracic echocardiographic evaluation of the left ventricle (LV) during anesthesia induction was performed. The primary endpoint was the decline in mean BP after anesthetic administration in telmisartan and valsartan groups. Multivariate logistic regression analysis was used to identify predictors of post-induction hypotension. RESULTS: Data from 157 patients undergoing noncardiac surgery were analyzed. No significant differences were found in mean BP decline between the two groups during anesthesia induction. Hemodynamic changes and LV ejection fraction (EF) during anesthesia induction were similar between the groups. Age and preoperative initial mean BP in operation room (OR) were associated with post-induction hypotension in both groups. CONCLUSIONS: The angiotensin receptor blocker (ARB) type did not influence post-induction hypotension during anesthesia induction. Age and preoperative initial mean BP in OR were associated with post-induction hypotension in patients taking ARBs.

Risk factors for early septic failure after two-stage exchange total knee arthroplasty for treatment of periprosthetic joint infection.

BACKGROUND: The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose of this study was to determine the surgical outcomes and the risk factors for early septic failure after two-stage revision TKA for chronic PJI. METHODS: We identified a total of 246 adult patients who met the Musculoskeletal Infection Society (MSIS) diagnostic criteria for chronic PJI at two academic tertiary hospitals from March 2012 to December 2018. Finally, 151 patients who consecutively received two-stage exchange revision TKA for chronic PJI and who had a minimum 3-year follow-up were enrolled and retrospectively reviewed. Successful surgical treatment was evaluated for two-stage revision TKA and risk factors for early septic failure were identified. RESULTS: Early septic failures occurred within 3 years after reimplantation in 48 patients (31.8%). After accounting for potentially confounding variables, we found that male patient [odds ratio (OR): 2.753, 95% confidence interval (CI) 1.099-6.893, p = 0.031], fungus or mycobacterial infection (OR: 5.224, 95% CI 1.481-18.433, p = 0.01), and positive culture at reimplantation (OR: 4.407, 95% CI 1.255-15.480, p = 0.021) were independently associated with early septic failure after two-stage exchange revision TKA. CONCLUSION: Male patients, fungus or mycobacterial infection, and positive culture at reimplantation were independently associated with an increased risk of early septic failure after two-stage exchange revision TKA despite normal C-reactive protein values prior to reimplantation. Further prospective and high-quality studies are needed to determine the risk factors of two-stage exchange revision TKA for chronic PJI. LEVEL OF EVIDENCE: level IV; retrospective comparison; treatment study.

Chemical Hypoxia Induces Pyroptosis in Neuronal Cells by Caspase-Dependent Gasdermin Activation.

Hypoxia-induced neuronal death is a major cause of neurodegenerative diseases. Pyroptosis is a type of inflammatory programmed cell death mediated by elevated intracellular levels of reactive oxygen species (ROS). Therefore, we hypothesized that hypoxia-induced ROS may trigger pyroptosis via caspase-dependent gasdermin (GSDM) activation in neuronal cells. To test this, we exposed SH-SY5Y neuronal cells to cobalt chloride (CoCl2) to trigger hypoxia and then evaluated the cellular and molecular responses to hypoxic conditions. Our data revealed that CoCl2 induced cell growth inhibition and the expression of hypoxia-inducible factor-1α in SH-SY5Y cells. Exposure to CoCl2 elicits excessive accumulation of cytosolic and mitochondrial ROS in SH-SY5Y cells. CoCl2-induced hypoxia not only activated the intrinsic (caspases-3, -7, and -9) apoptotic pathway but also induced caspase-3/GSDME-dependent and NLRP3/caspase-1/GSDMD-mediated pyroptosis in SH-SY5Y cells. Importantly, inhibition of caspase-3 and -1 using selective inhibitors ameliorated pyroptotic cell death and downregulated GSDM protein expression. Additionally, treatment with a ROS scavenger significantly suppressed caspase- and pyroptosis-related proteins in CoCl2-treated SH-SY5Y cells. Our findings indicate that hypoxia-mediated ROS production plays an important role in the activation of both apoptosis and pyroptosis in SH-SY5Y neuronal cells, thus providing a potential therapeutic strategy for hypoxia-related neurological diseases.

Preclinical evaluation of an 18F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis.

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE-/-) mice. The aortas ApoE-/- mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE-/- mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE-/- mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE-/- mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE-/- mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo.

Efficient and Inexpensive Synthesis of 15N-Labeled 2-Azido-1,3-dimethylimidazolinium Salts Using Na15NO2 Instead of Na15NNN.

15N-Labeled azides are important probes for infrared and magnetic resonance spectroscopy and imaging. They can be synthesized by reaction of primary amines with a 15N-labeled diazo-transfer reagent. We present the synthesis of 15N-labeled 2-azido-1,3-dimethylimidazolinium salts 1 as a 15N-labeled diazo-transfer reagent. Nitrosation of 1,3-dimethylimidazolinium-2-yl hydrazine (2) with Na15NO2 under acidic conditions gave 1 as a 1:1 mixture of α- and γ-15N-labeled azides, α- and γ-1, rather than γ-1 alone. The isotopomeric mixture thus obtained was then subjected to the diazo-transfer reaction with primary amines 3 to afford azides 4 as a 1:1 mixture of ß-15N-labeled azides ß-4 and unlabeled ones 4'. The efficient and inexpensive synthesis of 1 as a 1:1 mixture of α- and γ-1 using Na15NO2 instead of Na15NNN facilitates their wide use as a 15N-labeled diazo-transfer reagent for preparing 15N-labeled azides as molecular probes.

A novel Mycobacterium Tuberculosis antigen, MTB48 enhances inflammatory response in LPS-induced RAW264.7 macrophage immune cells.

Mtb (Mycobacterium tuberculosis) is a pathogenic bacterium that causes tuberculosis infection (TB). Mtb-secreted proteins have recently been investigated as virulence factors, as well as therapeutic and vaccine possibilities. The early-secreted antigen target MTB48 is one of these proteins that has been explored as a cocktail antigen in the serodiagnosis of active tuberculosis. However, there exists no information about the function or control of MTB48's inflammatory activity in macrophages at the site of inflammation. As a result, the goal of this research was to figure out what processes are involved in MTB48's function. MTB48 stimulated inflammation in LPS induced macrophages at both the protein and mRNA levels, which was interesting. MTB48 aided LPS induced IB phosphorylation and NF-κB translocation. MTB48 also led to the phosphorylation of MAPK signaling protein. These findings imply that MTB48 can enhance inflammatory activity via NF-κB and MAPK signaling by upregulating COX-2, iNOS, NO and PGE2. Many tuberculosis antigens have been tested for the development of rapid serological diagnosis. The results of this study suggest that MTB48 is a very high conservative antigen and is a major factor causing inflammatory reactions, suggesting that it can help control and diagnose tuberculosis.

Neoadjuvant Chemotherapy Prior to Radical Cystectomy for Muscle-Invasive Bladder Cancer With Variant Histology: A Systematic Review and Meta-Analysis of Survival Outcomes and Pathological Features.

PURPOSE: To conduct systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy (NAC) on survival and histopathological outcomes of variant histology (VH) of urothelial carcinoma (UC) of bladder. METHODS: This systematic review was registered in PROSPERO (CRD42023389115). Literature search was conducted in PubMed/Medline, Embase, and Cochrane Library for studies published up to January 2023. Population, intervention, comparator, outcome, and study design were as follows: bladder cancer patients with VH (population), neoadjuvant chemotherapy (intervention), radical cystectomy only (comparators), oncological survival and pathologic response (outcomes), and retrospective or prospective (study design). RESULTS: Finally, a total of 17 studies were included in the present study (quantitative analysis, n = 17; qualitative analysis, n = 12). Pooled HR was 0.49 (95% CI: 0.31-0.76; P = .002) for OS. Pooled HR was 0.61 (95% CI: 0.38-0.98; P = .04) for CSS. Pooled HR was 0.44 (95% CI: 0.21-0.93; P = .03) in PFS. Pooled OR was 6.61 (95% CI: 4.50-9.73; P < .00001) in complete pathologic response. Pooled OR was 9.59 (95% CI: 3.56-25.85; P < .00001) in any pathologic response. Evidence quality assessments for each 5 comparisons using the GRADE approach were that Certainty was moderate in 1, low in 1, and very low in 3. CONCLUSIONS: Administration of NAC before surgery in bladder cancer patients with VH might confer better survival outcomes and higher pathologic down staging rate than no administration of NAC before surgery.