Variable angle of insulated shotcrete under different loading rates and temperature and humidity cycles- shear test and analysis.

The new thermal insulating shotcrete is of great significance for the management of thermal damage in deep mines, and its own strength has a greater impact on the roadway insulation and safe production, so it is very necessary to study the shear strength of the new thermal insulating shotcrete under the influence of the deep hot and humid environment and the stress of mining. For the heat-insulating shotcrete, firstly, we carried out the concrete variable angle shear test under different loading rates, which concluded that the shear rate and peak shear stress showed a trend of increasing and then decreasing; as the angle increases, the different rates have a greater impact on the peak shear stress of the specimen. Secondly, the concrete variable angle shear test was carried out under the temperature and humidity cycle, which revealed that the shear strength of thermal insulated shotcrete increased firstly and then decreased with the increase of temperature at the same number of cycles. Finally, the empirical equations between the cohesive force c, the angle of internal friction ϕ and the number of warm and wet cycles n and the temperature of warm and wet cycles T are fitted with the MATLAB software respectively, and the research results provide technical references for the management of geothermal temperature in deep well projects.

Efficacy of the COVID-19 vaccination in patients with asymptomatic or mild illness during the Omicron epidemic in Guangzhou: a multi-centre retrospective cohort study.

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.

Structural basis for partial agonism in 5-HT3A receptors.

Hyperactivity of serotonin 3 receptors (5-HT3R) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HT3AR in complex with partial agonists (SMP-100 and ALB-148471) captured in pre-activated and open-like conformational states. Molecular dynamics simulations were used to assess the stability of drug-binding poses and interactions with the receptor over time. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists and antagonists of the 5-HT3AR.

Elevating Second Near-Infrared Photothermal Conversion Efficiency of Hollow Gold Nanorod for a Precise Theranostic of Orthotopic Bladder Cancer.

The second near-infrared (NIR-II) window laser-activated agents have attracted broad interest in an orthotopic cancer theranostic. However, developing NIR-II photothermal agents (PTAs) with advanced photothermal conversion efficiency (PTCE) and tumor-specific response elevation remains a crucial challenge. Herein, a hollow gold nanorod (AuHNR) with a strong localized surface plasmon resonance (LSPR) peak in the NIR-II window was coated with MnO2 and chitosan to obtain AuHNR@MnO2@CS (termed AuMC) by a one-step method. Upon exposure to the tumor microenvironment (TME), the overexpressed GSH triggered degradation of the MnO2 layer to release Mn2+ and resulted in the PTCE elevation owing to exposure of the AuHNR. Consequently, photoacoustic and magnetic resonance imaging for accurate diagnosis, Mn2+-mediated chemodynamic therapy, and AuHNR elevating PT therapy for precise treatment could be achieved. Both in vitro and in vivo experiments confirmed the good performance of the AuMC on an orthotopic bladder cancer precise theranostic. This study provided NIR-II activated, TME-response PT conversion efficiency enhanced PTAs and offered a tumor-selective theranostic agent for orthotopic bladder cancer in clinical application.

DNA Assembly of Plasmonic Nanostructures Enables In Vivo SERS-Based MicroRNA Detection and Tumor Photoacoustic Imaging.

Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo. These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.

Phylogenic evolution of beat perception and synchronization: a comparative neuroscience perspective.

The study of music has long been of interest to researchers from various disciplines. Scholars have put forth numerous hypotheses regarding the evolution of music. With the rise of cross-species research on music cognition, researchers hope to gain a deeper understanding of the phylogenic evolution, behavioral manifestation, and physiological limitations of the biological ability behind music, known as musicality. This paper presents the progress of beat perception and synchronization (BPS) research in cross-species settings and offers varying views on the relevant hypothesis of BPS. The BPS ability observed in rats and other mammals as well as recent neurobiological findings presents a significant challenge to the vocal learning and rhythm synchronization hypothesis if taken literally. An integrative neural-circuit model of BPS is proposed to accommodate the findings. In future research, it is recommended that greater consideration be given to the social attributes of musicality and to the behavioral and physiological changes that occur across different species in response to music characteristics.

Hollow microneedle microfluidic paper-based chip for biomolecules rapid sampling and detection in interstitial fluid.

The interstitial fluid (ISF) contains rich bioinformation for disease diagnosis and healthcare monitoring. However, the efficient sampling and detection of the biomolecules in ISF is still challenging. Herein, we develop a facile but versatile ISF analysis platform by combining controllable hollow microneedles (HMNs) and elaborate microfluidic paper-based analytical devices (µPADs). The HMNs and µPADs was fixed in a bottom PDMS layer. A top PDMS layer containing a cylindrical cavity to produce negative pressure for sampling was packaged on the bottom PDMS layer. The HMNs enable efficient and swift sampling of sufficient ISF to the µPADs through one-touch finger operation without extra manipulations. The µPADs realized to simultaneously detect glucose and lactic acid in the detection area to produce chromogenic agents and analyzed by the self-programed RGB application (APP) in smartphones. The HMN microfluidic paper-based chip provides a point-of-care platform for accurate detection of biomolecules in ISF, holding great promise in the development of wearable device.

NEAT1/MALAT1/XIST/PKD--Hsa-Mir-101-3p--DLGAP5 Axis as a Novel Diagnostic and Prognostic Biomarker Associated With Immune Cell Infiltration in Bladder Cancer.

Background: The clinical value of the biomarkers of bladder cancer (BC) is limited due to their low sensitivity or specificity. As a biomarker, DLG associated protein 5 (DLGAP5) is a potential cell cycle regulator in cancer cell carcinogenesis. However, its functional part in BC remains unclear. Therefore, this study aims to identify DLGAP5 expression in BC and its potential diagnostic and prognostic values. Eventually, it predicts the possible RNA regulatory pathways of BC. Methods: Data on DLGAP5 expression levels in BC and normal bladder tissues were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC), Kaplan-Meier survival curves, and the univariate and multivariate Cox regression analysis determined the diagnostic and prognostic values of DLGAP5 in BC patients. Finally, the StarBase predicted the target RNAs and constructed networks using Cytoscape. Results: DLGAP5 expression was significantly upregulated in BC tissue, verified by the TCGA (p < 0.001), GSE3167, GSE7476, and GSE65635 datasets (p < 0.01). BC patients with increased DLGAP5 had poor overall survival (OS) (p = 0.01), disease specific survival (DSS) (p = 0.006) and progress free interval (DFI) (p = 0.007). The area under the ROC curve (AUC) was 0.913. The multivariate Cox analysis identified that lymphovascular invasion (p = 0.007) and DLGAP5 (p = 0.002) were independent prognostic factors. Conclusion: Increased DLGAP5 expression was closely associated with a poor prognosis in BC patients. In this case, DLGAP5 might be a diagnostic and prognostic biomarker for BC. DLGAP5 expression might be regulated by NEAT1/MALAT1/XIST/PKD--Hsa-mir-101-3p pathways.

Preoperative antibiotic therapy exceeding 7 days can minimize infectious complications after percutaneous nephrolithotomy in patients with positive urine culture.

PURPOSE: To explore an appropriate duration of antibiotic therapy before percutaneous nephrolithotomy (PCNL) in patients with positive urine culture. METHODS: From March 2016 to May 2018, consecutive patients with positive urine culture undergoing PCNL were prospectively registered. Initial preoperative antibiotics were given empirically. If needed, antibiotics were upgraded or adjusted to susceptible antibiotic after obtaining antibiotic-sensitivity test. Postoperative systemic inflammatory response syndrome (SIRS) was the primary outcome. RESULTS: Among the 220 participants, the incidence of positive stone culture and SIRS were 85.5% and 36.8%. Escherichia coli (53.6%, 44.5%) and Proteus mirabilis (8.2%, 10.0%) were the top two bacteria in urine and stones. In univariable analysis, patients with postoperative SIRS had a higher rate of stone culture positivity (97.5% VS 78.4%, P < 0.001) and a shorter duration of preoperative antibiotics therapy (3.4 ± 2.7 days versus 4.2 ± 2.8 days, P = 0.037). The landscape of SIRS showed a declining trend as the elongation of preoperative antibiotics (P = 0.039). In a day-by-day comparison, SIRS was less prevalent in patients treated by pre-PCNL antibiotics ≥ 7 days than in those with antibiotics ≤ 6 days (21.7% VS 40.8%, P = 0.017). Multivariable logistic regression confirmed positive stone culture (P = 0.001, OR 11.115) as an independent risk factor and pre-PCNL antibiotics ≥ 7 days (P = 0.048, OR 0.449) as an independent protective factor for SIRS. Preoperative antibiotic ≥ 7 days decreased SIRS from 45.4 to 27.8% and from 9.1 to 0% in patients with a positive and negative stone culture, respectively. CONCLUSION: Exceeding seven days should be appropriate duration of antibiotic therapy before PCNL in patients with positive urine cultures.

Characteristics of Double-J Stent Encrustations and Factors Associated with their Development.

PURPOSE: To evaluate the chemical composition of double-J stent encrustation and to assess risk factors associated with their development. MATERIALS AND METHODS: Patients who had double-J stents removed between July 2016 and June 2017 were recruited for this study prospectively. The clinical features of the patients were recorded and the composition of encrustation material was analyzed by infrared spectroscopy. RESULTS: Encrustments from a total of 372 double-J stents were collected. The mean age of patients was 50.4±13.1 years and deposits possible to analyze were obtained from 228 males (61.3%) and 144 females (38.7%). Calcium oxalate monohydrate was the most common constituent of stone and encrustments. The encrustation rate of vesical coils was significantly higher than that of renal coils (P<0.001). There was no significant difference in chemical composition between stone and encrustation regarding renal (P=0.086) and vesical coils (P=0.072). The only predictive risk factor for the development of encrustation on double-J stents was indwelling time. This phenomenon was observed in both renal (P<0.001) and vesical coils (P=0.021). Interestingly, patient with chronic kidney disease (CKD) was associated with less risk of encrustation on both renal (P<0.001) and vesical coils (P=0.001). CONCLUSION: The chemical composition of double-J stent encrustation was the same as the urinary stone. The prevention strategy for stone composition is also suitable for the prevention of encrustation of double-J stent. The only predictive factor for double-J stent encrustation was the indwelling time. CKD patient was shown to be less at risk for the development of encrustation.

Enhanced Antibiotic Treatment Based on Positive Urine Dipstick Infection Test Before Percutaneous Nephrolithotomy Did Not Prevent Postoperative Infection in Patients with Negative Urine Culture.

Introduction: Urinary tract infection (UTI) should be treated before percutaneous nephrolithotomy (PCNL). However, the most appropriate treatment strategy in patients with negative urine culture but positive urine dipstick infection test (positive urinary leukocyte or nitrite reaction) remains unclear. Materials and Methods: From August 2016 to February 2018, 806 consecutive patients who had undergone the first-stage PCNL with negative urine culture were included. Preoperative urinalysis, antibiotic treatment, intraoperative stone culture, and postoperative systemic inflammatory response syndrome (SIRS) were prospectively recorded. The primary outcome was SIRS. The impact of preoperative antibiotics on preoperative UTI, stone culture, and postoperative SIRS was studied. Results: Among the 806 participants, the rate of positive urine dipstick infection test and SIRS were 26.8% and 7.2%, respectively. In univariable analysis, positive urinary nitrite (p < 0.001), positive urinary leukocytes (p < 0.001), positive urine dipstick infection test (p < 0.001), longer duration of pre-PCNL antibiotics (p = 0.001), higher level of pre-PCNL antibiotics (p = 0.010), infection stones (p = 0.001), and positive stone culture (p < 0.001) were risk factors for SIRS. However, multivariable analysis showed that positive stone culture (p = 0.004) and prolonged preoperative treatment with antibiotics (p = 0.021) were independent risk factors for SIRS. Although preoperative antibiotics reduced the incidence of positive urine leukocyte (p < 0.001) or nitrite reactions (p < 0.001), prolonged or upgraded preoperative antibiotics did not affect the incidence of positive stone culture. Whether stone culture was positive (p = 0.023) or negative (p = 0.025), prolonged preoperative treatment with antibiotics was associated with a higher incidence of SIRS. Conclusions: Enhanced preoperative antibiotic treatment based on positive urine dipstick infection tests was insufficient to reduce the incidence of positive stone culture but increased the risk of SIRS after PCNL in patients with negative urine cultures.

Ultrasensitive visual detection of Hg2+ ions via the Tyndall effect of gold nanoparticles.

This work reports a new methodology for naked-eye nanosensing of Hg2+ where the Tyndall effect of gold nanoparticles (GNPs) acts as a light scattering signalling readout. Its utility is demonstrated with ultrasensitive detection of the target with a limit down to 0.13 nM (∼5461-fold sensitivity improvement over conventional GNP-based methods with surface plasmon resonance signalling).

The characteristic and relationship of Escherichia coli isolated from urine and stones in patients with calcium oxalate stones.

Previous clinical studies have shown that Escherichia coli (E. coli) predominated in urine and stone culture from calcium oxalate (CaOx) stone disease. The characteristic and relationship between E. coli isolated from urine cultures (EUC) and stone cultures (ESC) are compared. 83 E. coli (33 EUC and 50 ESC, respectively) from 66 CaOx stone patients were recruited in the study. E. coli in urine and stones from those patients were assessed by antimicrobial susceptibility test, genotyping and phylogenetic grouping. Furthermore, whole genome sequencing and comparative genomic analysis in paired ESC and EUC isolated strains from eight patients were carried out. The E. coli strains from ESC and EUC were not only multidrug resistant (MDR), but also had the similar pattern of resistant genes. The dominant phylogenetic group was B2, which was found in 54.0% of the ESC samples and 69.7% of the EUC samples, respectively. The virulence genes of E. coli, which isolated from stones and urine in the same patients, were highly homologous and largely consistent. Meanwhile, these E. coli strains were located in the same clade originated from a common ancestor. ESC and EUC isolated from patients with CaOx stones had a high prevalence of phylogenetic groups B2. Bacterial strains isolated from urine and stones in the same patient had consistent antimicrobial susceptibility profiles, genotyping, phylogenetic groups, virulence and resistance genes, also with high sequence co-linearity and close relationships.

Is multiple tract percutaneous nephrolithotomy a safe approach for staghorn calculi?

PURPOSE: To explore the safety of multiple tract percutaneous nephrolithotomy (PNL) in terms of complication and draw a nomogram to predict the possibility of significant renal function decline (SRFD). MATERIALS AND METHODS: Patients with complex renal calculi appropriate for PNL at our institution between August 2016 and February 2018 were included in the study. The outcome of single and multiple tract PNL was analyzed retrospectively. A nomogram was created to predict the probability of SRFD. RESULTS: 793 (88.4%) patients were treated with single tract PNL (Group 1) and 104 patients (11.6%) treated with multiple tract PNL (Group 2). Group 2 had a significantly greater hemoglobin reduction (16.0 ± 12.5 vs. 11.4 ± 11.8 g/L, p < 0.001), higher rate of postoperative fever (19.2% vs. 11.9%, p = 0.034) and longer duration of the operation (110.6 ± 39.6 vs. 97.8 ± 34.5 min, p < 0.001). A nomogram for predicting the probability of SRFD was constructed based on identified risk factors: patients' age, positive urine culture (UC +), hemoglobin reduction and embolization. The area of receiver operating characteristic (ROC) curve was 70%. Bootstrapping technique utilized to make the calibration plot showed a high reliability of the nomogram. CONCLUSIONS: Multiple tract PNL had a higher risk of hemoglobin reduction and postoperative fever than single tract PNL. Multiple tracts had no effect on SRFD, but old age, UC + , hemoglobin reduction and embolization were risk factors for SRFD. A nomogram with the aim of predicting the probability of SRFD based on these parameters demonstrated good uniformity in internal validation.

Transforming glucose into fluorescent graphene quantum dots via microwave radiation for sensitive detection of Al3+ ions based on aggregation-induced enhanced emission.

This paper initially describes a nanosensor for fluorescence detection of Al3+ ions by using graphene quantum dots (GQDs) that are synthesized via microwave-assisted single-step ring-closure condensation of glucose molecules. The one-pot synthesis strategy based on the microwave radiation could be finished in several minutes and no post-modification of the GQDs was required. In particular, the GQD nanoprobes showed a sensitive and specific fluorescence enhancement response to Al3+. The involved mechanism might be the Al3+-mediated aggregation of the GQDs leading to aggregation-induced enhanced emission (AIEE). Under optimal conditions, this new fluorescent nanosensor was able to quantitatively detect Al3+ in a linear concentration range of 0.4-500 µM. The limit of detection was estimated to be ∼59.8 nM according to the 3σ rule, which made it be among the most sensitive systems currently available for sensing the target ion. Moreover, satisfactory recovery results (ranging from 96.8 to 109.7%) of analyzing a set of real water examples additionally validated its accuracy for practical applications. Considering its simplicity, high sensitivity and specificity, low cost, and good reliability, the developed fluorescent nanosensing system for Al3+ holds great promise for broad uses in water safety, environmental monitoring, and waste management.

CSTI-300 (SMP-100); a Novel 5-HT3 Receptor Partial Agonist with Potential to Treat Patients with Irritable Bowel Syndrome or Carcinoid Syndrome.

The 5-hydroxytryptamine (5-HT) (serotonin) 5-HT3 receptor represents a clinical target for antagonists to deliver symptomatic relief to patients with diarrhea-predominant irritable bowel syndrome (IBS-d) or carcinoid syndrome. Unfortunately, this pharmacological strategy can present side effects (e.g., severe constipation). The present study investigates the potential of a novel 5-HT3 receptor partial agonist, CSTI-300, to treat patients with IBS-d and other conditions associated with discomfort from colonic distension, with a predicted reduced side-effect profile. The in vitro and in vivo preclinical pharmacology of the drug CSTI-300 was investigated to explore the potential to treat patients with IBS-d. CSTI-300 displayed selective high affinity for the human and rat 5-HT3 receptor (Ki approximately 2.0 nM) and acted as a partial agonist (approximately 30%-50% intrinsic efficacy) in vitro. In an in vivo model of IBS-d, the rat colon distension model, CSTI-300 displayed dose-dependent efficacy. In addition, oral administration of CSTI-300 to dogs that achieved plasma levels of the drug exceeding the Ki value for the 5-HT3 receptor failed to either evoke emesis or alter the state of feces. Pharmacokinetics for CSTI-300 in rat and dog identified high levels of oral availability with t 1/2 range of 1.6-4.4 hours. The preclinical pharmacology of the lead candidate drug, CSTI-300, supports the potential of this novel drug to offer symptomatic relief to patients with irritable bowel syndrome and carcinoid syndrome with a rationale for a reduced "on-target" side-effect profile relative to 5-HT3 receptor antagonists, such as alosetron. SIGNIFICANCE STATEMENT: There is a lack of effective current treatment for diarrhea-predominant irritable bowel syndrome and carcinoid syndrome, and in both conditions, overactivity of the 5-hydroxytryptamine (5-HT) 5-HT3 receptor is thought to be implicated in the pathophysiology. Because 5-HT3 receptor blockade with antagonists results in significant side effects, we present evidence that treatment with a suitable 5-HT3 receptor partial agonist will alleviate some symptoms associated with these conditions yet, without fully inhibiting the receptor, predict a less pronounced side-effect profile associated with this therapeutic strategy.

Enhanced functional DNA biosensor for distance-based read-by-eye quantification of various analytes based on starch-hydrolysis-adjusted wettability change in paper devices.

Low-cost, equipment-free and quantitative detection of a wide range of analytes of interest at home and in the field holds the potential to revolutionize disease diagnosis, environmental pollution monitoring, and food safety analysis. Herein, we describe a functional DNA biosensor for the first time that integrates analyte-directed assembly of enzyme-coated microbead probes for robust yet efficient signal amplification with a simple quantitative detection motif of distance measurement on portable paper devices based on starch-hydrolysis-adjusted wettability change of paper. Its utility is well demonstrated with highly sensitive and specific detection of model analytes ranging from adenosine (an important small biomolecule; 1.6 µM detection limit) to interferon-γ (a protein marker; 0.3 nM detection limit) and Pb2+ (a highly toxic metal ion; 0.5 nM detection limit) by simply using an inexpensive, ubiquitous ruler. The developed general method with the distance-measuring readout should be easily tailored for the portable, read-by-eye, quantitative detection of many other types of analytical targets by taking advantage of their specific functional DNA partners like aptamers and DNAzymes.

Highly Sensitive Colorimetric Detection of a Variety of Analytes via the Tyndall Effect.

This work initially reports the use of a quite familiar optical phenomenon of colloidal solutions, namely, the Tyndall Effect (TE) as signal readout for highly sensitive colorimetric chemical and biological analysis. Taking gold nanoparticles (GNPs) as a model colloid, the TE-inspired assay (TEA) is developed based on the conversion of a specific recognition event (e.g., the aptamer-analyte binding) into the aggregation of GNPs, leading to a significant TE enhancement. In the TEA, a cheap laser pointer pen is used as a hand-held light source, while a smartphone serves as a portable quantitative reader. The results show that the TE signaling strategy achieves a ∼1000-fold sensitivity improvement compared with the most common surface plasmon resonance signaling method using GNPs. The utility of the TEA is well demonstrated with the inexpensive, rapid, and portable detection of trace levels of analytes ranging from an important small-molecule drug (cocaine, ∼1.5 pM detection limit) to a protein biomarker (interferon-γ, ∼2.2 fM detection limit) and a toxic metal ion (Ag+, ∼1.4 nM detection limit). In addition, as the TE enhancement simply stems from the aggregation of either bare (unmodified) or modified GNPs, the TEA is universally applicable to almost all of the existing GNP-based liquid-phase colorimetric assays. The TEA method developed herein lights a new way for equipment-free point-of-care analysis in various fields including medical diagnosis, food safety evaluation, and environmental monitoring, especially in the resource-poor areas of the world.

Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction.

A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C-N/C-C bond cleavage and two C-N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed.