Adverse events and efficacy of second-round CAR-T cell therapy in relapsed pediatric B-ALL.

OBJECTIVE: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment approach for pediatric patients suffering from relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, there was a paucity of data on the challenges associated with second-round CAR-T therapy in this population. METHODS: Medical records of nine pediatric patients who received second-round CAR-T therapy in a single center from June 2019 to May 2023 were analyzed. Throughout the course of the clinical trial, we evaluated adverse events including CRS, CRES, infections, hematologic toxicity, and organ injury, as well as CAR-T responses. RESULTS: Except for one patient who chose CART therapy due to testicular relapse, the remaining patients had indications for CAR-T therapy due to relapse with bone marrow alone or combined with other site. There were no difference between the transfusion dose of CART1 and CART2. No differences of incidence and grade of CRS was found between the first-round CAR-T therapy (CART1) and second-round CAR-T therapy (CART2). Additionally, we found that the incidence of CRES was higher for CART1(3/9,33.3%) than CART2(1/9,11.1%). Our findings revealed that there were no differences of IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α between CART1 and CART2, but the peak level of IL-17A was significantly higher in patients receiving CART1 compared to those receiving CART2 (p = .011). Early and late infection rates after CART1 were higher than CART2. Based on the dynamic changes of ANC, hemoglobin and platelet, ANC, and platelet were reduced obviously post CART. It seems that the incidences of severe thrombocytopenia and severe anemia were higher in the CART1 group compared to CART2. The MRD-negative CR rates for CART1 and CART2 are 100% and 44.4%, respectively (p = .029). All patients experienced events (relapse, chemotherapy, transplantation, or death) after receiving CART2, including one died, three discharged automatically, and the remaining five patients survived. CONCLUSION: Although the remission rate of CART2 is not as high as the CART1 due to the severity of the disease, its safety regarding CRS, CRES, infections, and organ injury is still excellent. Therefore, CART2 remains a viable option for treating pediatric relapsed B-ALL.

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF-κB/NLRP3 axis.

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. Nowadays, there are still no effective antiviral drugs for EV71 infection. High mobility group box 1 (HMGB1) is reported to be highly expressed in HFMD patients. However, the role and underlying mechanism of HMGB1 in EV71-associated HFMD are still unclear. HMGB1 expression was detected using RT-qPCR and western blot assays. Loss- and gain-function experiments were performed to evaluate the effects of HMGB1 on EV71-infected cells. The virus titer was examined by TCID50. CCK-8 and flow cytometry assays were applied to detect the cell viability and cell cycle. Oxidative stress was determined by relative commercial kits. HMGB1 level was elevated in the serum of EV71-infected patients with HFMD and EV71-induced RD cells. EV71 infection induced the transfer of HMGB1 from the nucleus into the cytoplasm. HMGB1 knockdown inhibited virus replication, viral protein (VP1) expression and promoted antiviral factor expression. In addition, the inhibition of HMGB1 improved cell viability, protected against S phase arrest, and inhibited EV71-induced cell injury and oxidative stress, whereas HMGB1 overexpression showed the opposite effects. In terms of mechanism, HMGB1 overexpression activated the TLR4/NF-κB/NLRP3 signaling pathway and promoted cell pyroptosis. The inhibition of TLR4 and NF-κB reversed the effects of HMGB1 overexpression on virus replication, oxidative stress, and pyroptosis. In conclusion, HMGB1 knockdown inhibits EV71 replication and attenuates pyroptosis through TLR4/NF-κB/NLRP3 axis.

The Predictive Value of a New Inflammatory-Nutritional Score for Quality of Life after Laparoscopic Distal Gastrectomy for Gastric Cancer.

We explored the predictive value of various inflammatory-nutritional indicators for postoperative quality of life (QoL) in gastric cancer (GC) patients undergoing laparoscopic distal gastrectomy (LDG) and developed a novel inflammatory-nutritional score (INS). In this study, 156 GC patients who underwent LDG were included. We used multiple linear regression to analyze the correlation between postoperative QoL and inflammatory-nutritional indicators. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct INS. Hemoglobin was positively correlated with physical functioning (ß =8.5; p = 0.003) and cognitive functioning (ß = 3.5; p = 0.038) 3 mo, after surgery. Prognostic nutritional index (PNI) was positively associated with global health status (ß =5.8; p = 0.043). Albumin-alkaline phosphatase ratio (AAPR) was negatively correlated with emotional functioning 12 mo, after surgery (ß = -5.7; p = 0.024). Neutrophil-lymphocyte ratio (NLR), Lymphocyte- monocyte ratio (LMR), AAPR, hemoglobin and PNI were selected using LASSO regression analysis to construct INS. The C-index values of the model in the training group and the validation group were 0.806 (95% CI, 0.719-0.893) and 0.758 (95% CI: 0.591-0.925), respectively. INS had particular predictive value for postoperative QoL in patients undergoing LDG and provided a reference for risk stratification and clinical practice.

The performance of VCS(volume, conductivity, light scatter) parameters in distinguishing latent tuberculosis and active tuberculosis by using machine learning algorithm.

BACKGROUND: Tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis (MTB) and is the ninth leading cause of death worldwide. It is still difficult to distinguish active TB from latent TB,but it is very important for individualized management and treatment to distinguish whether patients are active or latent tuberculosis infection. METHODS: A total of 220 subjects, including active TB patients (ATB, n = 97) and latent TB patients (LTB, n = 113), were recruited in this study .46 features about blood routine indicators and the VCS parameters (volume, conductivity, light scatter) of neutrophils(NE), monocytes(MO), and lymphocytes(LY) were collected and was constructed classification model by four machine learning algorithms(logistic regression(LR), random forest(RF), support vector machine(SVM) and k-nearest neighbor(KNN)). And the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) to estimate of the model's predictive performance for dentifying active and latent tuberculosis infection. RESULTS: After verification,among the four classifications, LR and RF had the best performance (AUROC = 1, AUPRC = 1), followed by SVM (AUROC = 0.967, AUPRC = 0.971), KNN (AUROC = 0.943, AUPRC = 0.959) in the training set. And LR had the best performance (AUROC = 0.977, AUPRC = 0.957), followed by SVM (AUROC = 0.962, AUPRC = 0.949), RF (AUROC = 0.903, AUPRC = 0.922),KNN(AUROC = 0.883, AUPRC = 0.901) in the testing set. CONCLUSIONS: The machine learning algorithm classifier based on leukocyte VCS parameters is of great value in identifying active and latent tuberculosis infection.

New scoring system combining computed tomography body composition analysis and inflammatory-nutritional indicators to predict postoperative complications in stage II-III colon cancer.

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.

Noninvasive Prediction of Ki-67 Expression in Hepatocellular Carcinoma Using Machine Learning-Based Ultrasomics: A Multicenter Study.

OBJECTIVES: To investigate the ability of ultrasomics to predict Ki-67 expression in hepatocellular carcinoma (HCC). METHODS: A total of 244 patients from three hospitals were retrospectively recruited (training dataset, n = 168; test dataset, n = 43; and validation dataset, n = 33). Lesion segmentation of the ultrasound images was performed manually by two radiologists. In total, 1409 ultrasomics features were extracted. Feature selection was conducted using the intra-class correlation coefficient, variance threshold, mutual information, and recursive feature elimination plus eXtreme Gradient Boosting. The support vector machine was combined with the learning curve and grid search parameter tuning to construct the clinical, ultrasomics, and combined models. The predictive performance of the models was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy. RESULTS: The ultrasomics model performed well on the training, test, and validation datasets. The AUC (95% confidence interval [CI]) for these datasets were 0.955 (0.912-0.981), 0.861 (0.721-0.947), and 0.665 (0.480-0.819), respectively. The combination of ultrasomics and clinical features significantly improved model performance on all three datasets. The AUC (95% CI), sensitivity, specificity, and accuracy were 0.986 (0.955-0.998), 0.973, 0.840, and 0.869 on the training dataset; 0.871 (0.734-0.954), 0.750, 0.829, and 0.814 on the test dataset; and 0.742 (0.560-0.878), 0.714, 0.808, and 0.788 on the validation dataset, respectively. CONCLUSIONS: Ultrasomics was proved to be a potential noninvasive method to predict Ki-67 expression in HCC.

Integrated Porous Cu Host Induced High-Stable Bidirectional Li Plating/Stripping Behavior for Practical Li Metal Batteries.

The double-sided electrodes with active materials are widely used for commercial lithium (Li) ion batteries with a higher energy density. Accordingly, developing an anode current collector that can accommodate the stable and homogeneous Li plating/stripping on both sides will be highly desired for practical Li metal batteries (LMBs). Herein, an integrated bidirectional porous Cu (IBP-Cu) film with a through-pore structure is fabricated as Li metal hosts using the powder sintering method. The resultant IBP-Cu current collector with tunable pore volume and size exhibits high mechanical flexibility and stability. The bidirectional and through-pore structure enables the IBP-Cu host to achieve homogeneous Li deposition and effectively suppresses the dendritic Li growth. Impressively, the as-fabricated Li/IBP-Cu anode exhibits a remarkable capacity of up to 7.0 mAh cm-2 for deep plating/stripping, outstanding rate performance, and ultralong cycling ability with high Coulombic efficiency of ≈100% for 1000 cycles. More practicably, a designed pouch cell coupled with one Li/IBP-Cu anode and two LiFePO4 cathodes exhibits a highly elevated energy density (≈187.5%) compared with a pouch cell with one anode and one cathode. Such design of a bidirectional porous Cu current collector with stable Li plating/stripping behaviors suggests its promising practical applications for next-generation Li metal batteries.

Genome-Wide Survey and Functional Verification of the NAC Transcription Factor Family in Wild Emmer Wheat.

The NAC transcription factor (TF) family is one of the largest TF families in plants, which has been widely reported in rice, maize and common wheat. However, the significance of the NAC TF family in wild emmer wheat (Triticum turgidum ssp. dicoccoides) is not yet well understood. In this study, a genome-wide investigation of NAC genes was conducted in the wild emmer genome and 249 NAC family members (TdNACs) were identified. The results showed that all of these genes contained NAM/NAC-conserved domains and most of them were predicted to be located on the nucleus. Phylogenetic analysis showed that these 249 TdNACs can be classified into seven clades, which are likely to be involved in the regulation of grain protein content, starch synthesis and response to biotic and abiotic stresses. Expression pattern analysis revealed that TdNACs were highly expressed in different wheat tissues such as grain, root, leaves and shoots. We found that TdNAC8470 was phylogenetically close to NAC genes that regulate either grain protein or starch accumulation. Overexpression of TdNAC8470 in rice showed increased grain starch concentration but decreased grain Fe, Zn and Mn contents compared with wild-type plants. Protein interaction analysis indicated that TdNAC8470 might interact with granule-bound starch synthase 1 (TdGBSS1) to regulate grain starch accumulation. Our work provides a comprehensive understanding of the NAC TFs family in wild emmer wheat and establishes the way for future functional analysis and genetic improvement of increasing grain starch content in wheat.

Predictive Value of CT Enterography Index for Postoperative Intra-abdominal Septic Complications in Patients With Crohn's Disease: Implications for Surgical Decision-Making.

BACKGROUND: Postoperative intra-abdominal septic complications in patients with Crohn's disease undergoing intestinal resection and anastomosis are frequent and difficult to manage. OBJECTIVE: This study sought to explore the value of preoperative CT enterography to predict intra-abdominal septic complications. DESIGN: This was a retrospective and prospective observational study. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: Patients with Crohn's disease undergoing primary intestinal resection were enrolled in our study. MAIN OUTCOME MEASURES: The CT enterography severity index was calculated and its ability to predict intra-abdominal septic complications evaluated by multivariate analyses. A prospective study was then performed to assess the reliability of this CT enterography index. RESULTS: The incidence of postoperative intra-abdominal septic complications in patients undergoing a 1-stage procedure was significantly higher than those undergoing a 2-stage procedure (3/103 vs 24/241; 2.9% vs 10.0%; p = 0.026). A multivariate analysis identified 5 CT enterography parameters, including mesenteric fibrofatty proliferation, intra-abdominal abscess or phlegmon, intestinal fistula, peritoneal effusion, and intestinal dilatation with stricture to be independent predictors of intra-abdominal septic complications (p < 0.001). A nomogram model based on these 5 parameters was constructed. A receiver operating characteristic analysis identified a CT enterography nomogram score cutoff of 175 as a predictor of intra-abdominal septic complications with a sensitivity of 83.3% and a specificity of 85.3%. In the prospective study, those patients with a CT enterography nomogram score >175 were assigned to the 2-stage group, which resulted in a similar intra-abdominal septic complication incidence in those undergoing intestinal resection with or without anastomosis (2/82 vs 2/34; p = 0.355). LIMITATIONS: This study was limited by its single-center scope. CONCLUSIONS: Preoperative CT enterography findings may predict postoperative outcomes and help determine surgical approach in Crohn's disease. Patients with worse intra-abdominal findings confirmed by CT enterography may benefit from stoma creation after intestinal resection. See Video Abstract at http://links.lww.com/DCR/B588. EL VALOR PREDICTIVO DEL NDICE ENTEROGRFICO POR TOMOGRAFA COMPUTADA PARA LAS COMPLICACIONES SPTICAS INTRAABDOMINALES POSTOPERATORIAS EN PACIENTES CON ENFERMEDAD DE CROHN IMPLICACIONES PARA LA TOMA DE DECISIONES QUIRRGICAS: ANTECEDENTES:Las complicaciones sépticas intra-abdominales postoperatorias en pacientes con enfermedad de Crohn sometidos a resección intestinal y anastomosis son frecuentes y difíciles de manejar.OBJETIVO:Este estudio buscó explorar el valor del índice enterográfico por tomografía computada en el pré-operatorio y así poder predecir futuras complicaciones sépticas intra-abdominales.DISEÑO:Estudio observacional retro-prospectivo.AJUSTE:Investigación realizada en un hospital de referencia terciaria.PACIENTES:Se incluyeron en nuestro estudio pacientes con enfermedad de Crohn sometidos a una resección intestinal primaria.PRINCIPALES MEDIDAS DE RESULTADO:Se calculó el índice de gravedad de la enterografía por tomografía axial computada y se evaluó su capacidad para predecir las complicaciones sépticas intra-abdominales mediante un análisis multivariado. Luego se realizó un estudio prospectivo para evaluar la confiabilidad del índice enterográfico por tomografía axial computada.RESULTADOS:La incidencia de complicaciones sépticas intra-abdominales postoperatorias en pacientes sometidos a un procedimiento de un solo tiempo fue significativamente mayor que aquellos sometidos a un procedimiento de dos tiempos (3/103 frente a 24/241; 2,9% frente a 10,0%; p = 0,026). El análisis multivariado identificó cinco parámetros enterográficos por tomografía axial computada, incluidos la proliferación fibrograsa mesentérica, el absceso o flegmón intra-abdominal, la fístula entérica, el derrame peritoneal y la dilatación intestinal debido a estenosis como predictores independientes de complicaciones sépticas intra-abdominales (p <0,001). Se construyó un modelo de Nomograma basado en estos cinco parámetros. Un análisis de las características operatorias del receptor identificó una puntuación de cohortes del nomograma de la enterografía por tomografía axial computada de 175 como predictor de complicaciones sépticas intra-abdominales con una sensibilidad del 83,3% y una especificidad del 85,3%. En el estudio prospectivo, los pacientes con puntuación de nomograma enterográfico por tomografía axial computada superior a 175 fueron asignados al grupo en dos tiempos, lo que resultó en una incidencia similar de complicaciones sépticas intra-abdominales en aquellos sometidos a resección intestinal con o sin anastomosis (2/82 vs. 2/34; p = 0,355).LIMITACIONES:Este estudio estuvo limitado por su alcance unicéntrico.CONCLUSIÓN:Los hallazgos enterográficos por tomografía axial computada pré-operatoria pueden predecir ciertos resultados postoperatorios y ayudar a determinar el abordaje quirúrgico en la enfermedad de Crohn. Los pacientes con peores hallazgos intra-abdominales confirmados por enterografía en la tomografía axial computada podrían beneficiarse de la creación de un estoma después de la resección intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B588. (Traducción-Dr Xavier Delgadillo).

Synthesis of Biaryls via Decarbonylative Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Aryl Anhydrides.

Transition metal-catalyzed cross-couplings have been widely employed in the synthesis of many important molecules in synthetic chemistry for the construction of diverse C-C bonds. Conventional cross-coupling reactions require active electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly enough. Herein, we disclose the first nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl anhydrides and arylboronic acids for the synthesis of biaryls in a decarbonylation manner. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process.

Dynamic prostatic and laser-ablated lesion volume change after transperineal laser ablation in canine: preliminary observation and its clinical significance.

AIM: The purpose of this study is to observe the volume change of prostate and laser-ablated lesions in the canine and to explore the mechanism and clinical significance through histopathology. MATERIALS AND METHODS: Transperineal laser ablation (TPLA) was performed under the guidance of transrectal ultrasound (TRUS) in eight canines. Two canines were sacrificed 1 day and 1 week after TPLA, respectively. The remaining six canines were sacrificed after finishing transrectal contrast-enhanced ultrasound (TR-CEUS) at three phases. RESULTS: The prostatic volumes immediately following TPLA and 1 week later were larger than before TPLA (20.1 ± 3.9 vs 17.1 ± 3.8 ml; 21.7 ± 3.6 vs 17.1 ± 3.8 ml, p < 0.05), but 1 month later, returned to the preoperative level (17.4 ± 3.2 ml). At three time points, the mean volumes of laser-ablated lesions at 3 W/600 J were 0.6 ± 0.2, 1.1 ± 0.4, and 1.7 ± 0.5 ml, respectively, while those of laser-ablated lesions at 3 W/1200 J were 1.2 ± 0.2, 1.6 ± 0.3, and 2.2 ± 0.5 ml, respectively. The mean volumes of laser-ablated lesions increased significantly over time after TPLA (p < 0.050). CONCLUSION: The prostate volume transient enlarges after TPLA, which prompts for clinical application that it should prolong appropriately the duration of urinary catheterization to avoid acute urinary retention. Many inflammatory cells were observed in the laser-ablated lesions and adjacent normal prostate parenchyma through histopathology. It is speculated that the inflammatory response is involved in the progression of tissue damage.

TiO2 and Co Nanoparticle-Decorated Carbon Polyhedra as Efficient Sulfur Host for High-Performance Lithium-Sulfur Batteries.

Metal organic frameworks (MOFs)-derived porous carbon is proposed as a promising candidate to develop novel, tailorable structures as polysulfides immobilizers for lithium-sulfur batteries because of their high-efficiency electron conductive networks, open ion channels, and abundant central ions that can store a large amount of sulfur and trap the easily soluble polysulfides. However, most central ions in MOFs-derived carbon framework are encapsulated in the carbon matrix so that their exposures as active sites to adsorb polysulfides are limited. To resolve this issue, highly dispersed TiO2 nanoparticles are anchored into the cobalt-containing carbon polyhedras that are converted from ZIF-67. Such a type of TiO2 and Co nanoparticles-decorated carbon polyhedras (CCo/TiO2 ) provide more exposed active sites and much stronger chemical trapping for polysulfides, hence improving the sulfur utilization and enhancing reaction kinetics of sulfur-containing cathode simultaneously. The sulfur-containing carbon polyhedras decorated with TiO2 nanoparticles (S@CCo/TiO2 ) show a significantly improved cycling stability and rate capability, and deliver a discharge capacity of 32.9% higher than that of TiO2 -free S@CCo cathode at 837.5 mA g-1 after 200 cycles.

Profile of Consecutive Fecal Calprotectin Levels in the Perioperative Period and Its Predictive Capacity for Early Endoscopic Recurrence in Crohn's Disease.

BACKGROUND: The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. OBJECTIVE: We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. DESIGN: This was a prospective observational study. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. RESULTS: The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 µg/g. LIMITATIONS: This is a single-center trial with a limited cohort of patients. CONCLUSIONS: The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.

Forging C-S Bonds through Nickel-Catalyzed Aryl Anhydrides with Thiophenols: Decarbonylation or Decarbonylation Accompanied by Decarboxylation.

A nickel-catalyzed decarbonylation or decarbonylation accompanied by decarboxylation cross-coupling reaction of aryl anhydrides with thiophenols as coupling partners was disclosed. This method is promoted by a commercially available, moisture-stable, and inexpensive nickel(II) precatalyst. The process can tolerate a variety of functional groups using ubiquitous aryl anhydrides as cross-coupling precursors to produce thioethers in moderate to excellent yields.

One-Pot Synthesis of N-Imidoyl-(1 H)-indoles via Palladium-Catalyzed Oxidative Insertion Domino Reaction with Isocyanide and Arylboronic Acid.

Efficient one-pot synthesis of N-imidoyl-(1 H)-indoles has been described, which is achieved by the palladium-catalyzed oxidative insertion of 2-(phenylethynyl)aniline, arylboronic acid, and isonitrile. This method provides a new way to synthesize N-imidoyl-(1 H)-indoles, which has a wide substrate scope, good functional group tolerance, and mild reaction condition.

A novel nomogram integrating body composition and inflammatory-nutritional markers for predicting postoperative complications in patients with adhesive small bowel obstruction.

Background: Postoperative complications in adhesive small bowel obstruction (ASBO) significantly escalate healthcare costs and prolong hospital stays. This study endeavors to construct a nomogram that synergizes computed tomography (CT) body composition data with inflammatory-nutritional markers to forecast postoperative complications in ASBO. Methods: The study's internal cohort consisted of 190 ASBO patients recruited from October 2017 to November 2021, subsequently partitioned into training (n = 133) and internal validation (n = 57) groups at a 7:3 ratio. An additional external cohort comprised 52 patients. Body composition assessments were conducted at the third lumbar vertebral level utilizing CT images. Baseline characteristics alongside systemic inflammatory responses were meticulously documented. Through univariable and multivariable regression analyses, risk factors pertinent to postoperative complications were identified, culminating in the creation of a predictive nomogram. The nomogram's precision was appraised using the concordance index (C-index) and the area under the receiver operating characteristic (ROC) curve. Results: Postoperative complications were observed in 65 (48.87%), 26 (45.61%), and 22 (42.31%) patients across the three cohorts, respectively. Multivariate analysis revealed that nutrition risk score (NRS), intestinal strangulation, skeletal muscle index (SMI), subcutaneous fat index (SFI), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) were independently predictive of postoperative complications. These preoperative indicators were integral to the nomogram's formulation. The model, amalgamating body composition and inflammatory-nutritional indices, demonstrated superior performance: the internal training set exhibited a 0.878 AUC (95% CI, 0.802-0.954), 0.755 accuracy, and 0.625 sensitivity; the internal validation set displayed a 0.831 AUC (95% CI, 0.675-0.986), 0.818 accuracy, and 0.812 sensitivity. In the external cohort, the model yielded an AUC of 0.886 (95% CI, 0.799-0.974), 0.808 accuracy, and 0.909 sensitivity. Calibration curves affirmed a strong concordance between predicted outcomes and actual events. Decision curve analysis substantiated that the model could confer benefits on patients with ASBO. Conclusion: A rigorously developed and validated nomogram that incorporates body composition and inflammatory-nutritional indices proves to be a valuable tool for anticipating postoperative complications in ASBO patients, thus facilitating enhanced clinical decision-making.

Assembly dynamics of eukaryotic plankton and bacterioplankton in the Yangtze River estuary: A hybrid community perspective.

Estuaries, acting as transitional habitats receiving species introductions from both freshwater and marine sources, undergo significant impacts from global climate changes. Planktonic microorganisms contribute significantly to estuarine biodiversity and ecological stability. These microorganisms primarily fall into three groups: eukaryotic plankton, particle-associated bacteria, and free-living bacteria. Understanding the structural characteristics and interactions within these subcommunities is crucial for comprehending estuarine dynamics. We collected samples from three distinct locations (< 0.1 PSU, 6.6 PSU, and 19 PSU) within the Yangtze River estuary. Samples underwent analysis for physicochemical indicators, while microbial communities were subjected to 16S/18S rRNA amplicon sequencing. Additionally, simulated mixing experiments were conducted using samples of varying salinities. Estuary samples, combined with simulated experiments, were employed to collectively examine the structural characteristics and assembly processes of estuarine microbes. Our research highlights the considerable impact of phylogenetic classification on prokaryotic behavior in these communities. We observed a transition in assembly processes from primarily stochastic for particle-associated bacteria to a predominant influence of homogeneous selection as salinity increased. Particle-associated bacterial communities exhibited a greater influence of stochastic processes compared to free-living bacteria, showcasing higher stability in diversity. The variations in composition and structure of estuarine microbial subcommunities were influenced by diverse environmental factors. Particle-associated bacteria displayed elevated network characterization values and established closer interactions with eukaryotic plankton. Structural equation modeling (SEM) analysis revealed that free-living bacteria displayed a heightened sensitivity to environmental factors and exerted a more significant influence on assembly processes and network characteristics. Simulated mixing in these environments resulted in the loss of species with similar microbial taxonomic relationships. The functioning of bacterioplankton is influenced by salinity and the processes governing their assembly, particularly in relation to different living states. These findings significantly contribute to our understanding of the intricate interplay between prokaryotic and eukaryotic plankton microorganisms in highly dynamic environments, laying a robust foundation for further exploration into the ecological mechanisms governing microbial dynamics in estuaries.

Deep learning model based on endoscopic images predicting treatment response in locally advanced rectal cancer undergo neoadjuvant chemoradiotherapy: a multicenter study.

PURPOSE: Neoadjuvant chemoradiotherapy has been the standard practice for patients with locally advanced rectal cancer. However, the treatment response varies greatly among individuals, how to select the optimal candidates for neoadjuvant chemoradiotherapy is crucial. This study aimed to develop an endoscopic image-based deep learning model for predicting the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. METHODS: In this multicenter observational study, pre-treatment endoscopic images of patients from two Chinese medical centers were retrospectively obtained and a deep learning-based tumor regression model was constructed. Treatment response was evaluated based on the tumor regression grade and was defined as good response and non-good response. The prediction performance of the deep learning model was evaluated in the internal and external test sets. The main outcome was the accuracy of the treatment prediction model, measured by the AUC and accuracy. RESULTS: This deep learning model achieved favorable prediction performance. In the internal test set, the AUC and accuracy were 0.867 (95% CI: 0.847-0.941) and 0.836 (95% CI: 0.818-0.896), respectively. The prediction performance was fully validated in the external test set, and the model had an AUC of 0.758 (95% CI: 0.724-0.834) and an accuracy of 0.807 (95% CI: 0.774-0.843). CONCLUSION: The deep learning model based on endoscopic images demonstrated exceptional predictive power for neoadjuvant treatment response, highlighting its potential for guiding personalized therapy.

KLRB1 defines an activated phenotype of CD4+ T cells and shows significant upregulation in patients with primary Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate the role of KLRB1 (CD161) in human CD4+ T cells and elucidate its significance in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood samples from 37 healthy controls and 44 pSS patients were collected. The publicly available single-cell RNA-Seq data from pSS patient PBMCs were utilized to analyse KLRB1 expression in T cells. KLRB1-expressing T lymphocyte subset proportions in pSS patients and healthy controls were determined by flow cytometry. CD25, Ki-67, cytokine secretion, and chemokine receptor expression in CD4+ KLRB1+ T cells were detected and compared with those in CD4+ KLRB1- T cells. Correlation analysis was conducted between KLRB1-related T-cell subsets and clinical indicators. ROC curves were generated to explore the diagnostic potential of KLRB1 for pSS. RESULTS: KLRB1 was significantly upregulated following T-cell activation, and Ki-67 and CD25 expression was significantly greater in CD4+ KLRB1+ T cells than in CD4+ KLRB1- T cells. KLRB1+ CD4+ T cells exhibited greater IL-17A, IL-21, IL-22, and IFN-γ secretion upon stimulation, and there were significantly greater proportions of CCR5+, CCR2+, CX3CR1+, CCR6+, and CXCR3+ cells among CD4+ KLRB1+ T cells than among CD4+ KLRB1- T cells. Compared with that in HCs, KLRB1 expression in CD4+ T cells was markedly elevated in pSS patients and significantly correlated with clinical disease indicators. CONCLUSION: KLRB1 is a characteristic molecule of the CD4+ T-cell activation phenotype. The increased expression of KLRB1 in the CD4+ T cells of pSS patients suggests its potential involvement in the pathogenesis of pSS and its utility as an auxiliary diagnostic marker for pSS.