Difference of carrier dynamics in a semiconductor saturable absorber mirror with and without B+ ion-implantation.

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

Simultaneous type III congenital esophageal atresia and patent ductus arteriosus in a low-weight patient: A case report.

BACKGROUND: We report a low-birth-weight child (1.8 kg) with neonatal type III congenital esophageal atresia (CEA) combined with symptomatic patent ductus arteriosus (PDA). After comprehensive evaluation, esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications, and arterial catheter ligation was performed at the same time. Concurrent surgery for CEA combined with PDA has not been clearly reported in the literature. CASE SUMMARY: We report a 6-day-old female child with type III CEA and PDA. The patient presented with foam at the mouth after birth, cough and shortness of breath after feeding. At another hospital, she was considered to have neonatal pneumonia, neonatal jaundice and congenital heart disease and transferred to our hospital. After iodine oil radiography of the esophagus and echocardiography we confirmed diagnosis of CEA and PDA. The diameter of the PDA was 8 mm, with obvious left to right shunting. We performed right rear extrapleural orificium fistula ligation and esophageal anastomosis, and ligation of PDA via left axilla straight incision after 5 d of hospitalization. The operations were successful, and the incision healed after 12 d, and the patient was discharged. We re-examined the patient 1 mo after surgery. She did not vomit when she ate rice flour. Esophageal angiography showed no stricture of the anastomotic stoma. The patient weighed 3.2 kg. CONCLUSION: For CEA patients with multiple risk factors, comprehensive, timely and accurate diagnosis and evaluation, and early treatment may improve prognosis.

Personalized Federated Learning Algorithm with Adaptive Clustering for Non-IID IoT Data Incorporating Multi-Task Learning and Neural Network Model Characteristics.

The proliferation of IoT devices has led to an unprecedented integration of machine learning techniques, raising concerns about data privacy. To address these concerns, federated learning has been introduced. However, practical implementations face challenges, including communication costs, data and device heterogeneity, and privacy security. This paper proposes an innovative approach within the context of federated learning, introducing a personalized joint learning algorithm for Non-IID IoT data. This algorithm incorporates multi-task learning principles and leverages neural network model characteristics. To overcome data heterogeneity, we present a novel clustering algorithm designed specifically for federated learning. Unlike conventional methods that require a predetermined number of clusters, our approach utilizes automatic clustering, eliminating the need for fixed cluster specifications. Extensive experimentation demonstrates the exceptional performance of the proposed algorithm, particularly in scenarios with specific client distributions. By significantly improving the accuracy of trained models, our approach not only addresses data heterogeneity but also strengthens privacy preservation in federated learning. In conclusion, we offer a robust solution to the practical challenges of federated learning in IoT environments. By combining personalized joint learning, automatic clustering, and neural network model characteristics, we facilitate more effective and privacy-conscious machine learning in Non-IID IoT data settings.

Effective and Selective Ru(II)-Arene Complexes Containing 4,4'-Substituted 2,2' Bipyridine Ligands Targeting Human Urinary Bladder Cancer Cells.

Cisplatin-based chemotherapy is a common regimen for bladder cancer, a life-threatening cancer with more than 500,000 new cases worldwide annually. Like many other metallodrugs, cisplatin causes severe side effects for its general toxicity. Organoruthenium is known for its structural stability, good anticancer activity, and possible low general toxicity. Here, we have prepared and characterized a series of water-soluble ruthenium-arene complexes with N,N'-chelating ligands: [Ru(II)-η6-arene-(4,4'-(X)2-2,2'-bipyridine)Cl]Cl (arene = p-cymene, X = C4H9 (1), COOH (2), COOCH3 (3), COOC2H5 (4); arene = benzene, X = C4H9 (5), COOCH3 (6), COOC2H5 (7)). These complexes are carefully characterized using single-crystal X-ray diffraction, UV-vis, IR, 1H NMR, and MALDI-TOF MS spectroscopy. Their DFT-calculated structural and thermodynamic properties are consistent with the experimental observations. Biophysicochemical studies of complex interaction with CTDNA and BSA supported by molecular docking simulations reveal suitable properties of 1-7 as anticancer agents. Cytotoxicities of 1-7 are evaluated on healthy human MCF-10a-breast epithelial and African green monkey Vero cells, and carcinoma human HepG-2-hepatic, T24-bladder, and EAhy-926-endothelial cells. All complexes exhibit much higher cytotoxicity for T24 than cisplatin. Particularly, 1 and 2 are also highly selective toward T24. Fluorescence imaging and flow cytometry demonstrate that 1 and 2 penetrate T24 cell membrane and induce early apoptosis at their respective IC50 concentrations, which ultimately lead to cell death. Statistical analysis suggests that the order of importance for T24 cell antiproliferation is protein binding, Log p, Ru-Cl bond length, while DNA binding is the least important. This study is the first to report the anti-bladder cancer efficacy of Ru-arene-2,2'-bipyridine complexes, and may provide insights for rational design of organoruthenium drugs in the enduring search for new chemotherapeutic agents.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer.

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

Exploring the mechanism of action of lysine 5,6-aminomutase using EPR and ENDOR spectroscopies.

Radical enzymes orchestrate challenging chemical transformations by devising strategies to tame the highly reactive radical intermediates. Electron paramagnetic resonance (EPR) spectroscopy is the most suitable technique to study various aspects of the radical enzymes. Lysine 5,6-aminomutase (5,6-LAM) is one such radical enzyme and employs coenzyme B12 and pyridoxal 5'-phosphate (PLP) to catalyze the 1,2-amino shift reaction through a radical mechanism. 5,6-LAM accepts either d-lysine or l-ß-lysine as the substrate. EPR and electron nuclear double resonance (ENDOR) spectroscopies have played major roles in deciphering the mechanism of action of 5,6-LAM, while density functional theoretical (DFT) computation and synthetic isotopologues have played supporting roles. This comprehensive toolkit has revealed that 5,6-LAM undergoes large-scale conformational movement to bring PLP and coenzyme B12 close together, which allows the reaction to progress. The conformational change also closes the active site, which protects the radical intermediates and enables their transformation to product without unwanted side reactions. The substrate-related radical (S•), which is spin-coupled with Co2+ generated from homolysis of the CoC bond in coenzyme B12, was unequivocally characterized when a substrate analog, 4-thia-l-lysine, and isotopologues of it were reacted with 5,6-LAM. Studies with substrate analogs revealed a unique "odd-even" correlation with opening of the closed state. Moreover, mutagenesis studies identified the contributions that conserved residues in 5,6-LAM make toward binding of the substrate. Further studies with a cofactor analog, PLP-N-oxide, have shed light on various aspects of the mechanism of action of 5,6-LAM.

The Nitrogen Atom of Vitamin B6 Is Essential for the Catalysis of Radical Aminomutases.

Radical aminomutases are pyridoxal 5'-phosphate (PLP, a B6 vitamer)-dependent enzymes that require the generation of a 5'-deoxyadenosyl radical to initiate the catalytic cycle, to perform a 1,2 amino group shift reaction. The role of the nitrogen atom of PLP in radical aminomutases has not been investigated extensively yet. We report an alternative synthetic procedure to provide easy access to 1-deazaPLP (dAPLP), an isosteric analog of PLP which acts as a probe for studying the role of the nitrogen atom. Our results revealed that lysine 5,6-aminomutase (5,6-LAM), a radical aminomutase, reconstituted with dAPLP cannot turn over a substrate, demonstrating that the nitrogen atom is essential for radical aminomutases. In contrast, biochemical and spectroscopic studies on the S238A variant reconstituted with PLP revealed a minuscule loss of activity. This apparent anomaly can be explained by a water-mediated rescue of activity in S238A, as if mimicking the active site of lysine 2,3-aminomutase. This study leads to a better comprehension of how enzymes harness the optimum capability of PLP to realize catalysis.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Comparison of Magnesium and Titanium Doping on Material Properties and pH Sensing Performance on Sb2O3 Membranes in Electrolyte-Insulator-Semiconductor Structure.

In this research, electrolyte-insulator-semiconductor (EIS) capacitors with Sb2O3 sensing membranes were fabricated. The results indicate that Mg doping and Ti-doped Sb2O3 membranes with appropriate annealing had improved material quality and sensing performance. Multiple material characterizations and sensing measurements of Mg-doped and Ti doping on Sb2O3 sensing membranes were conducted, including of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). These detailed studies indicate that silicate and defects in the membrane could be suppressed by doping and annealing. Moreover, compactness enhancement, crystallization and grainization, which reinforced the surface sites on the membrane and boosted the sensing factor, could be achieved by doping and annealing. Among all of the samples, Mg doped membrane with annealing at 400 °C had the most preferable material properties and sensing behaviors. Mg-doped Sb2O3-based with appropriate annealing are promising for future industrial ionsensing devices and for possible integration with Sb2O3-based semiconductor devices.

Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy.

BACKGROUND: Cancer-testis genes can serve as prognostic biomarkers and valuable targets for immunotherapy in multiple tumors because of their restricted expression in testis and cancer. However, their expression pattern in hepatocellular carcinoma is still not well understood. The purpose is to comprehensively characterize the cancer-testis gene expression in hepatocellular carcinoma as well as identify prognostic markers and potential targets for immunotherapy. METHODS: Cancer-testis database and publicly available data sets reporting new cancer-testis genes were integrated, and then restricted them in a testis and hepatocellular carcinoma expression pattern. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of cancer-testis genes. Clustering analysis and coexpression analysis were performed to illustrate cancer-testis gene expression patterns in hepatocellular carcinoma. The association of gene expression of each cancer-testis gene to the corresponding methylation status was detected. Finally, we explored the associations between cancer-testis genes and CD8+ T-cell infiltration in hepatocellular carcinoma by TISIDB, and then validated it in an independent hepatocellular carcinoma cohort with 72 patients. RESULTS: A total of 59 testis-specific genes were identified highly expressed in hepatocellular carcinoma. Pathway enrichment analysis revealed that cancer-testis genes in hepatocellular carcinoma significantly involves in the process of cell cycle regulation. Most of the cancer-testis genes were coexpressed, and cluster analysis suggested that cancer-testis gene expressed in hepatocellular carcinoma is independent of sex, hepatitis status, and histology type. We also found that demethylation might be a regulatory mechanism of cancer-testis gene expression in hepatocellular carcinoma. Survival analysis indicated that cancer-testis genes could predict the prognosis of patients with hepatocellular carcinoma. Furthermore, BUB1B was identified contributing to the resistance of CD8+ T-cell infiltration in hepatocellular carcinoma and was an independent prognostic factor both for overall survival and disease-free survival. CONCLUSIONS: Our analysis enables better understanding of cancer-testis genes in hepatocellular carcinoma and provides potential targets for hepatocellular carcinoma treatment. Experimental and clinical studies are needed for further validations.

Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive pathological pattern of prostate cancer (PCa). We investigated the association of IDC-P in prostate biopsy (PBx) with several pathological features after radical prostatectomy (RP) and its prognostic value in high-risk PCa. A total of 418 patients with high-risk PCa after RP were included in this study. IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification. Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features. Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P. IDC-P was identified in PBx in 36/418 (8.6%) patients. Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP, including Gleason score 8-10 (P < 0.001), seminal vesicular invasion (P < 0.001), and pathological T (pT) 3a (P = 0.043). Patients with IDC-P in PBx manifested poorer biochemical-free survival (BFS) than those without IDC-P (37.47 months vs not reached, P < 0.001). The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools. We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa. In addition, IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.

Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.

This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml-1, had worse prognoses if EPE was detected. In patients with PSA <50 ng ml-1, EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: a real-world retrospective study.

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

Magnetic field effects on coenzyme B12- and B6-dependent lysine 5,6-aminomutase: switching of the J-resonance through a kinetically competent radical-pair intermediate.

The environmental magnetic field is beneficial to migratory bird navigation through the radical-pair mechanism. One of the continuing challenges in understanding how magnetic fields may perturb biological processes is that only a very few field-sensitive examples have been explored despite the prevalence of radical pairs in enzymatic reactions. We show that the reaction of adenosylcobalamin- and pyridoxal-5'-phosphate-dependent lysine 5,6-aminomutase proceeds via radical-pair intermediates and is magnetic field dependent. The 5'-deoxyadenosyl radical from adenosylcobalamin abstracts a C5(H) from the substrate to yield a {cob(ii)alamin - substrate} radical pair wherein the large spin-spin interaction (2J = 8000 gauss) locks the radical pair in a triplet state, as evidenced by electron paramagnetic resonance spectroscopy. Application of an external magnetic field in the range of 6500 to 8500 gauss triggers intersystem crossing to the singlet {cob(ii)alamin - substrate} radical-pair state. Spin-conserved H back-transfer from deoxyadenosine to the substrate radical yields a singlet {cob(ii)alamin-5'-deoxyadenosyl} radical pair. Spin-selective recombination to adenosylcobalamin decreased the enzyme catalytic efficiency kcat/Km by 16% at 7600 gauss. As a mechanistic probe, observation of magnetic field effects successfully demonstrates the presence of a kinetically significant radical pair in this enzyme. The study of a pronounced high-field level-crossing characteristic through an immobilized radical pair with a constant exchange interaction deepens our understanding of how a magnetic field may interact with an enzyme.

Development and validation of a convenient formula evaluating the value and applicability of medical literature in clinical practice.

OBJECTIVE: Evidence-based medicine offers explicit methods to evaluate the evidence grades of literature. However, evidence grades do not meet all the practical needs of physicians. This study is aimed to develop a convenient method for evaluating the clinical value of medical literature from the perspective of the clinician. METHODS: A literature applicability equation was formulated through the Delphi method and the analytic hierarchy process. A consistency check was used to ascertain the efficacy of the formula. Three senior clinicians assessed 30 articles based on their clinical experiences and subjective opinions, while one independent researcher performed independent assessments of the applicability of 30 articles using the evaluation formula. RESULTS: The literature applicability equation was Y = 3.93X1 + 11.78X2 + 14.83X3 + 44.53X4 + 24.93X5, where Y = literature applicability, X1 = years since publication, X2 = target question covered or not, X3 = sample size, X4 = study type, and X5 = journal quality. Consistency index (CI) values for the first-level indicator ("literature applicability") and the second-level indicators ("pertinence and timeliness" and "quality of results") were 0.0325, 0.0012, and 0.0001, respectively. The weights used to calculate the matrix indicators had satisfactory accordance (random coincidence coefficient = 0.056). A consistency check for the efficacy of the formula revealed kappa = 0.749 and P < .001. Conclusion : The developed and validated literature applicability evaluation formula may be a useful and convenient tool for identifying clinically valuable medical literature.