Silver-Catalyzed Decarboxylative Nitrooxylation of Aliphatic Carboxylic Acids.

Here, we present a silver-catalyzed decarboxylative nitrooxylation via a radical-based approach. The substrate scope of this reaction prototype extends to nonactivated primary and secondary carboxylic acids. This protocol provides a practical method for the synthesis of an unprecedented family of organic nitrates and exhibits wide functional group compatibility. Preliminary mechanistic studies reveal that a high-valent silver(II) nitrate complex is a versatile NO3 resource pool, allowing for facile C-O bond formation.

Electrochemical Decarboxylative Cross-Coupling with Nucleophiles.

Decarboxylative cross-coupling reactions are powerful tools for carbon-heteroatom bonds formation, but typically require pre-activated carboxylic acids as substrates or heteroelectrophiles as functional groups. Herein, we present an electrochemical decarboxylative cross-coupling of carboxylic acids with structurally diverse fluorine, alcohol, H2O, acid, and amine as nucleophiles. This strategy takes advantage of the ready availability of these building blocks from commercial libraries, as well as the mild and oxidant-free conditions provided by electrochemical system. This reaction demonstrates good functional-group tolerance and its utility in late-stage functionalization.

AKI-Pro score for predicting progression to severe acute kidney injury or death in patients with early acute kidney injury after cardiac surgery.

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.

Natural products for the treatment of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. PURPOSE: There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. STUDY DESIGN AND METHODS: PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. RESULTS: The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. CONCLUSION: Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.

Effect of addition of γ-poly glutamic acid on bacterial nanocellulose production under agitated culture conditions.

BACKGROUND: Bacterial nanocellulose (BNC), a natural polymer material, gained significant popularity among researchers and industry. It has great potential in areas, such as textile manufacturing, fiber-based paper, and packaging products, food industry, biomedical materials, and advanced functional bionanocomposites. The main current fermentation methods for BNC involved static culture, as the agitated culture methods had lower raw material conversion rates and resulted in non-uniform product formation. Currently, studies have shown that the production of BNC can be enhanced by incorporating specific additives into the culture medium. These additives included organic acids or polysaccharides. γ-Polyglutamic acid (γ-PGA), known for its high polymerization, excellent biodegradability, and environmental friendliness, has found extensive application in various industries including daily chemicals, medicine, food, and agriculture. RESULTS: In this particular study, 0.15 g/L of γ-PGA was incorporated as a medium additive to cultivate BNC under agitated culture conditions of 120 rpm and 30 â„ƒ. The BNC production increased remarkably by 209% in the medium with 0.15 g/L γ-PGA and initial pH of 5.0 compared to that in the standard medium, and BNC production increased by 7.3% in the medium with 0.06 g/L γ-PGA. The addition of γ-PGA as a medium additive resulted in significant improvements in BNC production. Similarly, at initial pH levels of 4.0 and 6.0, the BNC production also increased by 39.3% and 102.3%, respectively. To assess the characteristics of the BNC products, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis were used. The average diameter of BNC fibers, which was prepared from the medium adding 0.15 g/L γ-PGA, was twice thicker than that of BNC fibers prepared from the control culture medium. That might be because that polyglutamic acid relieved the BNC synthesis from the shear stress from the agitation. CONCLUSIONS: This experiment held great significance as it explored the use of a novel medium additive, γ-PGA, to improve the production and the glucose conversion rate in BNC fermentation. And the BNC fibers became thicker, with better thermal stability, higher crystallinity, and higher degree of polymerization (DPv). These findings lay a solid foundation for future large-scale fermentation production of BNC using bioreactors.

PCAO2: an ontology for integration of prostate cancer associated genotypic, phenotypic and lifestyle data.

Disease ontologies facilitate the semantic organization and representation of domain-specific knowledge. In the case of prostate cancer (PCa), large volumes of research results and clinical data have been accumulated and needed to be standardized for sharing and translational researches. A formal representation of PCa-associated knowledge will be essential to the diverse data standardization, data sharing and the future knowledge graph extraction, deep phenotyping and explainable artificial intelligence developing. In this study, we constructed an updated PCa ontology (PCAO2) based on the ontology development life cycle. An online information retrieval system was designed to ensure the usability of the ontology. The PCAO2 with a subclass-based taxonomic hierarchy covers the major biomedical concepts for PCa-associated genotypic, phenotypic and lifestyle data. The current version of the PCAO2 contains 633 concepts organized under three biomedical viewpoints, namely, epidemiology, diagnosis and treatment. These concepts are enriched by the addition of definition, synonym, relationship and reference. For the precision diagnosis and treatment, the PCa-associated genes and lifestyles are integrated in the viewpoint of epidemiological aspects of PCa. PCAO2 provides a standardized and systematized semantic framework for studying large amounts of heterogeneous PCa data and knowledge, which can be further, edited and enriched by the scientific community. The PCAO2 is freely available at https://bioportal.bioontology.org/ontologies/PCAO, http://pcaontology.net/ and http://pcaontology.net/mobile/.

Interferometric polarization compensation based on one single polarization-maintaining fiber.

In an interferometry system based on one single polarization-maintaining fiber (PMF), defects like the laser's ellipticity, the alignment error between the PMF and the laser source, and the PMF's internal stress will cause the emitted light from the PMF to be incompletely linearly polarized, resulting in nonlinear errors that cannot be ignored. This paper proposes a novel method that can realize polarization compensation for heterodyne interferometry, reduce the ellipticity of the emitted light, and thereby reduce the nonlinear error of the system. When using a PMF with an Extinction Ratio (ER) of 22 dB, the experimental results show that this method can reduce the polarization and increase the ER to 33.95 dB. After polarization compensation, the nonlinear error is reduced from 7.22 nm to 2.02 nm. The proportion of the nonlinear error reduction reaches to 71.99%, which greatly improves the accuracy of the system.

Comparing efficacies of different exercises on androgen deprivation therapy adverse effects in prostate cancer patients: a network meta-analysis.

INTRODUCTION: Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS: Literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL). 19 studies (1184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS: NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI [0.38; 11.46]) and resistance exercise (RE) (MD = 5.62, 95% CI [2.70; 8.55]) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI [-17.67; -4.11]) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI [78.75; 157.25]) and chest strength (MD = 13.30 [4.07; 22.53]). RE ranked first for strength improvements of leg and chest. CONCLUSION: ART showed better efficacy for the QoL, and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.

RARPKB: a knowledge-guide decision support platform for personalized robot-assisted surgery in prostate cancer.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has emerged as a pivotal surgical intervention for the treatment of prostate cancer (PCa). However, the complexity of clinical cases, heterogeneity of PCa, and limitations in physician expertise pose challenges to rational decision-making in RARP. To address these challenges, the authors aimed to organize the knowledge of previously complex cohorts and establish an online platform named the RARP knowledge base (RARPKB) to provide reference evidence for personalized treatment plans. MATERIALS AND METHODS: PubMed searches over the past two decades were conducted to identify publications describing RARP. The authors collected, classified, and structured surgical details, patient information, surgical data, and various statistical results from the literature. A knowledge-guided decision-support tool was established using MySQL, DataTable, ECharts, and JavaScript. ChatGPT-4 and two assessment scales were used to validate and compare the platform. RESULTS: The platform comprised 583 studies, 1589 cohorts, 1 911 968 patients, and 11 986 records, resulting in 54 834 data entries. The knowledge-guided decision support tool provide personalized surgical plan recommendations and potential complications on the basis of patients' baseline and surgical information. Compared with ChatGPT-4, RARPKB outperformed in authenticity (100% vs. 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), matching of patients (100% vs. 0%), and personalized recommendations for complications (100% vs. 20%). Postuse, the average System Usability Scale score was 88.88±15.03, and the Net Promoter Score of RARPKB was 85. The knowledge base is available at: http://rarpkb.bioinf.org.cn . CONCLUSIONS: The authors introduced the pioneering RARPKB, the first knowledge base for robot-assisted surgery, with an emphasis on PCa. RARPKB can assist in personalized and complex surgical planning for PCa to improve its efficacy. RARPKB provides a reference for the future applications of artificial intelligence in clinical practice.

Dimethyl sulfate and diisopropyl sulfate as practical and versatile O-sulfation reagents.

O-Sulfation is a vital post-translational modification in bioactive molecules, yet there are significant challenges with their synthesis. Dialkyl sulfates, such as dimethyl sulfate and diisopropyl sulfate are commonly used as alkylation agents in alkaline conditions, and result in the formation of sulfate byproducts. We report herein a general and robust approach to O-sulfation by harnessing the tunable reactivity of dimethyl sulfate or diisopropyl sulfate under tetrabutylammonium bisulfate activation. The versatility of this O-sulfation protocol is interrogated with a diverse range of alcohols, phenols and N-OH compounds, including carbohydrates, amino acids and natural products. The enhanced electrophilicity of the sulfur atom in dialkyl sulfates, facilitated by the interaction with bisulfate anion (HSO4-), accounts for this pioneering chemical reactivity. We envision that our method will be useful for application in the comprehension of biological functions and discovery of drugs.

High-intensity interval training versus moderate-intensity continuous training for localized prostate cancer under active surveillance: a systematic review and network meta-analysis.

BACKGROUND: High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been increasingly adopted for localized prostate cancer (PCa) under active surveillance (AS). However, it is unclear which training modality is the most favorable in terms of cardiorespiratory fitness and biochemical progression. METHODS: We searched PubMed, Cochrane and Embase for relevant RCTs. PRISMA guideline was adopted to ensure optimal conduct of this study. Serum prostate specific antigen (PSA) and peak VO2 were selected as primary outcomes and PSA doubling time (PSADT) and testosterone were selected as secondary outcomes. Only articles written in English were included. Cochrane risk-of-bias tool was used for risk of bias evaluation. RESULTS: A total of 501 studies were selected. Six RCTs with 222 patients were included for data extraction and analysis. High-intensity interval training (HIIT) group demonstrated significantly lower PSA compared with usual care (UC) (MD = -1.4; 95%CI = -2.77 to -0.03) and moderate-intensity continuous training (MICT) group (MD = -1.67; 95%CI = -3.30 to -0.05). Both HIIT and MICT showed significantly improved peak VO2 compared with UC. No significant difference was observed in PSADT and testosterone among different training modalities and UC. Regarding peak VO2, MICT had the highest surface under cumulative ranking curve (SUCRA) scores (98.1%). For serum PSA, HIIT had the highest probability (97.8%) to be the training with the highest efficacy. The potential source of bias mainly came from poorly performed allocation concealment and blinding strategies. CONCLUSIONS: The present study indicated that HIIT and MICT showed considerable cardiorespiratory benefits for localized PCa. HIIT was preferred over MICT in biochemical progression control in terms of decreasing serum PSA levels. However, MICT was favored over HIIT regarding cardiorespiratory benefits. The findings of this study may facilitate future lifestyle intervention, particularly in the form of physical training, for individuals diagnosed with localized PCa under AS.

Recent Advances in Implantable Neural Interfaces for Multimodal Electrical Neuromodulation.

Electrical neuromodulation plays a pivotal role in enhancing patient outcomes among individuals suffering from neurological disorders. Implantable neural interfaces are vital components of the electrical neuromodulation system to ensure desirable performance; However, conventional devices are limited to a single function and are constructed with bulky and rigid materials, which often leads to mechanical incompatibility with soft tissue and an inability to adapt to the dynamic and complex 3D structures of biological systems. In addition, current implantable neural interfaces utilized in clinical settings primarily rely on wire-based techniques, which are associated with complications such as increased risk of infection, limited positioning options, and movement restrictions. Here, the state-of-art applications of electrical neuromodulation are presented. Material schemes and device structures that can be employed to develop robust and multifunctional neural interfaces, including flexibility, stretchability, biodegradability, self-healing, self-rolling, or morphing are discussed. Furthermore, multimodal wireless neuromodulation techniques, including optoelectronics, mechano-electrics, magnetoelectrics, inductive coupling, and electrochemically based self-powered devices are reviewed. In the end, future perspectives are given.

Performance of ChatGPT on Chinese national medical licensing examinations: a five-year examination evaluation study for physicians, pharmacists and nurses.

BACKGROUND: Large language models like ChatGPT have revolutionized the field of natural language processing with their capability to comprehend and generate textual content, showing great potential to play a role in medical education. This study aimed to quantitatively evaluate and comprehensively analysis the performance of ChatGPT on three types of national medical examinations in China, including National Medical Licensing Examination (NMLE), National Pharmacist Licensing Examination (NPLE), and National Nurse Licensing Examination (NNLE). METHODS: We collected questions from Chinese NMLE, NPLE and NNLE from year 2017 to 2021. In NMLE and NPLE, each exam consists of 4 units, while in NNLE, each exam consists of 2 units. The questions with figures, tables or chemical structure were manually identified and excluded by clinician. We applied direct instruction strategy via multiple prompts to force ChatGPT to generate the clear answer with the capability to distinguish between single-choice and multiple-choice questions. RESULTS: ChatGPT failed to pass the accuracy threshold of 0.6 in any of the three types of examinations over the five years. Specifically, in the NMLE, the highest recorded accuracy was 0.5467, which was attained in both 2018 and 2021. In the NPLE, the highest accuracy was 0.5599 in 2017. In the NNLE, the most impressive result was shown in 2017, with an accuracy of 0.5897, which is also the highest accuracy in our entire evaluation. ChatGPT's performance showed no significant difference in different units, but significant difference in different question types. ChatGPT performed well in a range of subject areas, including clinical epidemiology, human parasitology, and dermatology, as well as in various medical topics such as molecules, health management and prevention, diagnosis and screening. CONCLUSIONS: These results indicate ChatGPT failed the NMLE, NPLE and NNLE in China, spanning from year 2017 to 2021. but show great potential of large language models in medical education. In the future high-quality medical data will be required to improve the performance.

Well-Dispersed Bi nanoparticles for promoting the lithium storage performance of Si Anode: Effect of the bridging Bi nanoparticles.

Silicon (Si) is considered a promising anode material for lithium-ion batteries (LIBs) due to its high theoretical specific capacity of up to 4200 mAh/g. However, the poor cycling and rate performances of Si induced by the low intrinsic electronic conductivity and large volume expansion during the lithiation/delithiation process limit its practical application. Herein, a novel silicon/bismuth@nitrogen-doped carbon (Si/Bi@NC) composite with nanovoids was synthesized and investigated as an advanced anode material for LIBs. In such a structure, ultrafine bismuth nanoparticles coupled with an N-doped carbon layer were introduced to modify the surface of Si nanoparticles. Subsequently, the lithiated LixBi has excellent high ionic conductivity and acts as a fast transport bridge for lithium ions. The introduced carbon coating layer and nanovoids can buffer the volume expansion of Si during the lithiation/delithiation process, thus maintaining structural stability during the cycling process. As a result, the Si/Bi@NC composite exhibits excellent electrochemical performance, providing a relatively high capacity of 955.8 mAh/g at 0.5 A/g after 450 cycles and excellent rate performance with a high capacity of 477.8 mAh/g even at 10.0 A/g. Furthermore, the assembled full cell with LiFePO4 as cathode and pre-lithium Si/Bi@NC as anode can provide a high capacity of 138.8 mAh/g at 1C after 90 cycles, exhibiting outstanding cycling performance.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Involvement of CXC chemokines (CXCL1-CXCL17) in gastric cancer: Prognosis and therapeutic molecules.

Gastric cancer (GC) is the fifth-most prevalent and second-most deadly cancer worldwide. Due to the late onset of symptoms, GC is frequently treated at a mature stage. In order to improve the diagnostic and clinical decision-making processes, it is necessary to establish more specific and sensitive indicators valuable in the early detection of the disease whenever a cancer is asymptomatic. In this work, we gathered information about CXC chemokines and GC by using scientific search engines including Google Scholar, PubMed, SciFinder, and Web of Science. Researchers believe that GC chemokines, small proteins, class CXC chemokines, and chemokine receptors promote GC inflammation, initiation, and progression by facilitating angiogenesis, tumor transformation, invasion, survival, metastatic spread, host response safeguards, and inter-cell interaction. With our absolute best professionalism, the role of CXC chemokines and their respective receptors in GC diagnosis and prognosis has not been fully explained. This review article updates the general characteristics of CXC chemokines, their unique receptors, their function in the pathological process of GC, and their potential application as possible indicators for GC. Although there have only recently been a few studies focusing on the therapeutic efficacy of CXC chemokine inhibitors in GC, growing experimental evidence points to the inhibition of CXC chemokines as a promising targeted therapy. Therefore, further translational studies are warranted to determine whether specific antagonists or antibodies designed to target CXC chemokines alone or in combination with chemotherapy are useful for diagnosing advanced GC.

Characteristics of deceleration capacity and deceleration runs in vasovagal syncope.

PURPOSE: Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks. METHODS: A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls. RESULTS: Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7 ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40 bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167-0.989; P = 0.048), daytime DC ≥ 7.37 ms (OR 3.040, 95% CI 1.220-7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138-0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS. CONCLUSION: Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.

Molecular insights into substrate promiscuity of CotA laccase catalyzing lignin-phenol derivatives.

CotA laccases are multicopper oxidases known for promiscuously oxidizing a broad range of substrates. However, studying substrate promiscuity is limited by the complexity of electron transfer (ET) between substrates and laccases. Here, a systematic analysis of factors affecting ET including electron donor acceptor coupling (ΗDA), driving force (ΔG) and reorganization energy (λ) was done. Catalysis rates of syringic acid (SA), syringaldehyde (SAD) and acetosyringone (AS) (kcat(SAD) > kcat(SA) > kcat(AS)) are not entirely dependent on the ability to form phenol radicals indicated by ΔG and λ calculated by Density Functional Theory (SA < SAD ≈ AS). In determined CotA/SA and CotA/SAD structures, SA and SAD bound at 3.9 and 3.7 Å away from T1 Cu coordinating His419 ensuring a similar ΗDA. Abilities of substrate to form phenol radicals could mainly account for difference between kcat(SAD) and kcat(SA). Furthermore, substrate pocket is solvent exposed at the para site of substrate's phenol hydroxyl, which would destabilize binding of AS in the same orientation and position resulting in low kcat. Our results indicated shallow partially covered binding site with propensity of amino acids distribution might help CotA discriminate lignin-phenol derivatives. These findings give new insights for developing specific catalysts for industrial application.

From molecular mechanisms of prostate cancer to translational applications: based on multi-omics fusion analysis and intelligent medicine.

Prostate cancer is the most common cancer in men worldwide and has a high mortality rate. The complex and heterogeneous development of prostate cancer has become a core obstacle in the treatment of prostate cancer. Simultaneously, the issues of overtreatment in early-stage diagnosis, oligometastasis and dormant tumor recognition, as well as personalized drug utilization, are also specific concerns that require attention in the clinical management of prostate cancer. Some typical genetic mutations have been proved to be associated with prostate cancer's initiation and progression. However, single-omic studies usually are not able to explain the causal relationship between molecular alterations and clinical phenotypes. Exploration from a systems genetics perspective is also lacking in this field, that is, the impact of gene network, the environmental factors, and even lifestyle behaviors on disease progression. At the meantime, current trend emphasizes the utilization of artificial intelligence (AI) and machine learning techniques to process extensive multidimensional data, including multi-omics. These technologies unveil the potential patterns, correlations, and insights related to diseases, thereby aiding the interpretable clinical decision making and applications, namely intelligent medicine. Therefore, there is a pressing need to integrate multidimensional data for identification of molecular subtypes, prediction of cancer progression and aggressiveness, along with perosonalized treatment performing. In this review, we systematically elaborated the landscape from molecular mechanism discovery of prostate cancer to clinical translational applications. We discussed the molecular profiles and clinical manifestations of prostate cancer heterogeneity, the identification of different states of prostate cancer, as well as corresponding precision medicine practices. Taking multi-omics fusion, systems genetics, and intelligence medicine as the main perspectives, the current research results and knowledge-driven research path of prostate cancer were summarized.

Electrophysiological Characteristics and Ablation Outcomes in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Catheter ablation of premature ventricular contractions (PVCs) that trigger polymorphic ventricular tachycardia (PVT) or ventricular fibrillation has been reported as a novel therapy to reduce the syncope events in patients with catecholaminergic PVT, whereas the long-term ablation outcome and its value in improving exercise-induced ventricular arrhythmias remain unclear. METHODS AND RESULTS: Fourteen consecutive selected patients with catecholaminergic PVT (mean±SD age, 16±6 years; 43% male patients) treated with maximum ß-blockers with no possibility of adding flecainide were prospectively enrolled for catheter ablation. The primary end point was syncope recurrence, and the secondary end point was the reduction of the ventricular arrhythmia score during exercise testing. Twenty-six PVT/ventricular fibrillation-triggering PVCs were identified for ablation. The trigger beats arose from the left ventricle in 50% of the cases and from both ventricles in 36% of the cases. Purkinje potentials were observed at 27% of the targets. After a mean follow-up of 49 months after ablation, 8 (57%) patients were free from syncope recurrence. Ablation of trigger beat significantly reduced the syncope frequency (mean±SD, 4.3±1.6 to 0.5±0.8 events per year; P<0.001) and improved the ventricular arrhythmia scores at the 3-month (5 [range, 3-6] to 1.5 [range, 0-5]; P=0.002) and 12-month (5 [range, 3-6] to 2 [range, 0-5]; P=0.014) follow-ups. The induction of nontriggering PVCs postablation was closely associated with syncope recurrence (hazard ratio, 6.8 [95% CI, 1.3-35.5]; P=0.026). CONCLUSIONS: Catheter ablation of PVT/ventricular fibrillation-triggering PVCs in patients with catecholaminergic PVT who cannot receive flecainide treatment seems to be a safe and feasible adjunctive treatment that may reduce the syncope burden and improve exercise-related ventricular arrhythmias. Induction of nontriggering PVCs after ablation is associated with a higher risk of syncope recurrence.