Publications by authors named "Li Di"

795 Publications

A machine learning-based approach for Low-Density Lipoprotein Cholesterol calculation using age, and lipid parameters.

Clin Chim Acta 2022 Aug 12. Epub 2022 Aug 12.

Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Low-density lipoprotein cholesterol (LDL-C) is a critical biomarker for cardiovascular disease. However, no consensus exists on the best method for estimating LDL-C in Chinese laboratories. This study aimed to develop a machine learning (ML) method for LDL-C estimation.

Methods: An extensive data set of 111448 samples were randomized into five equal subsets. ML-based equations were developed using age, sex, and lipid parameters based on five-fold cross-validation. The trained ML equations were externally validated in three different data sets. The performance of the ML equations was compared with the Friedewald, Martin/Hopkins, and Sampson equations.

Results: The selected ML equations showed less bias with direct LDL-C than other LDL-C equations in the Chinese population, including those with triglycerides (TG) ≥400 mg / dL and LDL-C < 40 mg / dL. The performance of the ML equations was less susceptible to age. External validation showed the generalization of the ML equations.

Conclusions: This study highlights the potential of integrating sex, age, and lipid parameters into the ML equations to obtain a more robust and reliable LDL-C calculation.
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http://dx.doi.org/10.1016/j.cca.2022.08.007DOI Listing
August 2022

Ten-year follow-up of lung cancer patients with resected adenocarcinoma in situ or minimally invasive adenocarcinoma: Wedge resection is curative.

J Thorac Cardiovasc Surg 2022 Jul 5. Epub 2022 Jul 5.

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Objective: This study aimed to reveal the long-term outcomes of patients with lung cancer with adenocarcinoma in situ or minimally invasive adenocarcinoma after resection, in the context of the different surgical resection types.

Methods: Patients with lung adenocarcinoma who underwent resection between December 2007 and December 2012 were reviewed. Patients with pathological adenocarcinoma in situ or minimally invasive adenocarcinoma were enrolled. Postoperative survival and risk of developing second primary lung cancer were analyzed.

Results: After reevaluating the histological findings of 1696 patients with lung adenocarcinoma, we enrolled 53 with adenocarcinoma in situ and 72 with minimally invasive adenocarcinoma for analyses. Of all 125 patients with adenocarcinoma in situ/minimally invasive adenocarcinoma, 86 (68.8%) were female, 114 (91.2%) were nonsmokers, and most of them (78, 62.4%) underwent wedge resection. The median follow-up period after surgery was 111 months. The 10-year recurrence-free survivals of adenocarcinoma in situ and minimally invasive adenocarcinoma were all 100%, and the 10-year overall survivals of adenocarcinoma in situ and minimally invasive adenocarcinoma were 98.1% and 97.2%, respectively. There was no difference in 10-year recurrence-free survival between patients who underwent lobectomy and wedge resection. EGFR mutations were detected in 63.1% (41/65) of patients who underwent mutational analysis. The risks of developing second primary lung cancer for adenocarcinoma in situ and minimally invasive adenocarcinoma 10 years after resection were 8.4% and 4.3% (P = .298), respectively, and were not correlated with EGFR mutation status (P = .525).

Conclusions: Pathological adenocarcinoma in situ and minimally invasive adenocarcinoma have no recurrence during 10-year follow-up after resection, regardless of surgical procedure types. Surgery is curative for these patients, and wedge resection is the preferred surgical procedure for nodules in the proper location.
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http://dx.doi.org/10.1016/j.jtcvs.2022.06.017DOI Listing
July 2022

Comprehensive analysis of mutational profile and prognostic significance of complex glandular pattern in lung adenocarcinoma.

Transl Lung Cancer Res 2022 Jul;11(7):1337-1347

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Complex glandular pattern (CGP) was included as high-grade pattern in the new grading system proposed by The International Association for the Study of Lung Cancer. We aimed to investigate the mutational profile and validate the prognostic significance and proper cut-off value to distinguish the aggressive behavior of CGP.

Methods: CGP was defined as nests of tumor cells with sieve-like perforation, fused glands with irregular borders or back-to-back glands without intervening stroma. Patients were categorized into four groups according to the percentage of CGP component (0%, 1-19%, 20-49%, 50-100%). Cox's proportional hazards model was applied to analyze recurrence free survival (RFS) and overall survival (OS).

Results: A total of 950 patients with resected lung adenocarcinoma was enrolled. The most frequent driver mutation in this cohort was and was detected in 624 (65.7%) patients. mutation was more frequently observed in patients with <20% CGP than in patients with ≥20% CGP (73.6% 60.2%), while mutation and rearrangement was significantly associated with ≥20% CGP. Patients with 20% or greater CGP exhibited significant worse RFS (P<0.001) and OS (P<0.001) than their counterparts. Moreover, the multivariate Cox regression analysis confirmed that CGP (≥20%) was a risk factor for a worse RFS (P=0.001) and OS (P<0.001) independent of staging and gene mutation. Smaller portion of CGP (<20%) were comparable in RFS and OS to those without CGP (0%). There was also no significant difference in RFS and OS between the 20-49% and ≥50% group.

Conclusions: Our study provided mutational profile of patients with different CGP, validated CGP as a negative prognostic factor and provided extra evidences for the optimal cut-off value of CGP percentage.
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http://dx.doi.org/10.21037/tlcr-22-127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359943PMC
July 2022

Transmembrane Protein ANTXR1 Regulates -Globin Expression by Targeting the Wnt/-Catenin Signaling Pathway.

J Immunol Res 2022 30;2022:8440422. Epub 2022 Jul 30.

School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China.

Reactivation of fetal hemoglobin (HbF, 22) alleviates clinical symptoms in patients with -thalassemia and sickle cell disease, although the regulatory mechanisms of -globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated -globin levels. However, the exact mechanism by which ANTXR1 regulates -globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34, and HUDEP-2 cells decreased and increased -globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, 22) in K562, cord blood CD34, and adult peripheral blood CD34 cells through interaction with LRP6 to promote the nuclear entry of -catenin and activate the Wnt/-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on -globin and Wnt/-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of -catenin in the Wnt pathway, but LiCl inhibits GSK3-. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing -globin. Our findings may provide a new intervention target for the treatment of -hemoglobinopathies.
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http://dx.doi.org/10.1155/2022/8440422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356848PMC
August 2022

Highly Integrated Multiplexing and Buffering Electronics for Large Aperture Ultrasonic Arrays.

BME Front 2022 30;2022. Epub 2022 Jun 30.

Molecular Imaging Program at Stanford University, Stanford, CA, USA.

Large aperture ultrasonic arrays can be implemented by tiling together multiple pretested modules of high-density acoustic arrays with closely integrated multiplexing and buffering electronics to form a larger aperture with high yield. These modular arrays can be used to implement large 1.75D array apertures capable of focusing in elevation for uniform slice thickness along the axial direction which can improve image contrast. An important goal for large array tiling is obtaining high yield and sensitivity while reducing extraneous image artifacts. We have been developing tileable acoustic-electric modules for the implementation of large array apertures utilizing Application Specific Integrated Circuits (ASICs) implemented using 0.35 m high voltage (50 V) CMOS. Multiple generations of ASICs have been designed and tested. The ASICs were integrated with high-density transducer arrays for acoustic testing and imaging. The modules were further interfaced to a Verasonics Vantage imaging system and were used to image industry standard ultrasound phantoms. The first-generation modules comprise ASICs with both multiplexing and buffering electronics on-chip and have demonstrated a switching artifact which was visible in the images. A second-generation ASIC design incorporates low switching injection circuits which effectively mitigate the artifacts observed with the first-generation devices. Here, we present the architecture of the two ASIC designs and module types as well imaging results that demonstrate reduction in switching artifacts for the second-generation devices.
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http://dx.doi.org/10.34133/2022/9870386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348545PMC
June 2022

Synergetic effect of photocatalysis and peroxymonosulfate activated by MFeO (M = Co, Mn, or Zn) for enhanced photocatalytic activity under visible light irradiation.

RSC Adv 2022 Jul 21;12(32):20946-20955. Epub 2022 Jul 21.

Instrument Analysis Center, Xi'an University of Architecture and Technology Xi'an 710055 China.

Nanosized MFeO (M = Co, Mn, or Zn) photocatalysts were synthesized a simple sol-gel method. MFeO photocatalysts exhibited lower photocatalytic activity for the degradation of levofloxacin hydrochloride under visible light irradiation. For enhancement of photocatalytic activity, MFeO was used to activate peroxymonosulfate and degrade levofloxacin hydrochloride under visible light irradiation. The influences of peroxymonosulfate dosage, levofloxacin hydrochloride concentration, pH value, and temperature on peroxymonosulfate activation to degrade levofloxacin hydrochloride were investigated in detail. The mechanism of activation of peroxymonosulfate by MFeO was proposed and proved by radical quenching experiments, electron spin resonance analysis, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and transient photocurrent responses. The combined activation effects of photogenerated e/h and transition metals on peroxymonosulfate to produce sulfate radical clearly enhanced the degradation efficiency.
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http://dx.doi.org/10.1039/d2ra03558hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301941PMC
July 2022

Application of optical coherence tomography in decision-making of post-thrombectomy adjunctive treatments.

J Neurointerv Surg 2022 Jul 26. Epub 2022 Jul 26.

Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

An adult patient with acute basilar artery occlusion underwent mechanical thrombectomy. After complete reperfusion, a 70% residual stenosis of the proximal basilar artery was observed. Intravascular optical coherence tomography (OCT) identified lipid plaques with an intact fibrous cap and thrombus in the culprit lesion, indicating plaque erosion was the mechanism of in situ thrombosis. Adjunctive antiplatelet therapy rather than rescue interventions was pursued for its beneficial effects in acute coronary syndrome caused by plaque erosion. The patient had a 90-day modified Rankin Scale score of 0. OCT enables precise evaluation of vessel characteristics following thrombectomy, so may improve outcomes through subsequent tailored treatments.
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http://dx.doi.org/10.1136/jnis-2022-019195DOI Listing
July 2022

Discovery of Isoindoline Amide Derivatives as Potent and Orally Bioavailable ADAMTS-4/5 Inhibitors for the Treatment of Osteoarthritis.

ACS Pharmacol Transl Sci 2022 Jul 22;5(7):458-467. Epub 2022 Jun 22.

Shanghai Hengrui Pharmaceutical Co. Ltd., 279 Wenjing Road, Shanghai 200245, China.

Osteoarthritis (OA) treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function. Starting from the reported ADAMTS-5 inhibitor GLPG1972, we applied a scaffold hopping strategy to generate a novel isoindoline amide scaffold. Representative compound showed high potency in ADATMS-4/5 inhibition, as well as good selectivity over a panel of other metalloproteases. In addition, compound exhibited excellent druglike properties and showed better pharmacokinetic (PK) profiles than GLPG1972 cross-species. Compound demonstrated dose-dependent efficacy in two rat osteoarthritis models.
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http://dx.doi.org/10.1021/acsptsci.2c00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274773PMC
July 2022

Pyrimidine-conjugated fluoroquinolones as new potential broad-spectrum antibacterial agents.

Bioorg Med Chem Lett 2022 Jul 11;73:128885. Epub 2022 Jul 11.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address:

Pyrimidine-conjugated fluoroquinolones were constructed to cope with the dreadful resistance. Most of the target pyrimidine derivatives effectively suppressed the growth of the tested strains, especially, 4-aminopyrimidinyl compound 1c showed a broad antibacterial spectrum and low cytotoxicity and exhibited superior antibacterial potency against Enterococcus faecalis with a low MIC of 0.25 μg/mL to norfloxacin and ciprofloxacin. The active compound 1c with fast bactericidal potency could inhibit the formation of biofilms and showed much lower trend for the development of drug-resistance than norfloxacin and ciprofloxacin. Further exploration revealed that compound 1c could prompt ROS accumulations in bacterial cells and interact with DNA to form a DNA-1c complex, thus facilitating bacterial death. ADME analysis indicated that compound 1c possessed favorable drug-likeness and promising pharmacokinetic properties. These results demonstrated that pyrimidine-conjugated fluoroquinolones held hope as potential antibacterial candidates and deserve further study.
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http://dx.doi.org/10.1016/j.bmcl.2022.128885DOI Listing
July 2022

Raised circulating soluble growth differentiation factor 15 is negatively associated with testosterone level in hypogonadic men with type 2 diabetes.

Diabetes Metab Res Rev 2022 Jul 8:e3564. Epub 2022 Jul 8.

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Aims: Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor-15 (GDF-15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF-15 levels and hypogonadism in Chinese male patients with T2DM.

Materials And Methods: A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF-15 and total testosterone concentrations were quantified by an enzyme-linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF-15 levels and hypogonadism in these patients.

Results: When compared with T2DM patients without hypogonadism circulating GDF-15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p < 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p < 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF-15 and testosterone deficiency were -1.795 (-2.929, -0.661). Serum GDF-15 levels were also associated positively with testosterone deficiency in each logistic regression model (p < 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p < 0.01).

Conclusions: In hypogonadal men with T2DM, an elevated serum GDF-15 level is associated negatively with serum testosterone concentration. GDF-15 may be a novel cytokine related to T2DM men with hypogonadism.
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http://dx.doi.org/10.1002/dmrr.3564DOI Listing
July 2022

[Spatial Variation and Potential Sources of Microplastics in Rivers in Tongzhou District, Beijing].

Huan Jing Ke Xue 2022 Jul;43(7):3656-3663

State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.

Microplastics are emerging contaminants, which can also absorb other contaminants, threatening the health of river ecosystems. However, research on the pollution of microplastics in rivers in northern China is still lacking. In this study, based on the sampling and analysis of water samples in 19 sites in six rivers in Tongzhou district, Beijing, the composition, spatial variation, and potential sources of microplastics were explored. The results showed that all sites were contaminated by microplastics, and the abundance of microplastics in the Xiaozhong River was the highest among all sites (3.50×10 n·m), which was 4.04 times that in the Yunchaojian River. The proportion of microplastics with particle sizes smaller than 2000 μm was 90.49%, and microplastics with particle sizes larger than 4000 μm were only found in two out of 19 sampling sites. The microplastics were fiber, film, fragment, and granule shaped. The proportion of fiber microplastics was the highest (90.23%) among all shapes. Most (84.29%) of the microplastics were transparent and blue. Rayon was the most common microplastic in each site, and its proportion in each site was over 66.67%. The proportions of other types of microplastics differed largely among different sites. Spatially, the abundance and types of microplastics in the upper reaches were higher than those in the lower reaches. According to spatial variations in shapes, types, colors, and abundance of microplastics, the potential sources of microplastics were identified. The potential sources of fiber microplastics were washing clothing and using fishing gear and dust-proof nets.
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http://dx.doi.org/10.13227/j.hjkx.202110130DOI Listing
July 2022

Neural mechanisms of aberrant self-referential processing in patients with generalized anxiety disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2022 Jul 1;119:110595. Epub 2022 Jul 1.

Department of Radiology, First Affiliated Hospital to Army Medical University, Chongqing, China; MOE Key Lab for Neuroinformation; High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

Massive theoretical studies in clinical psychology have implicated the self in understanding internalizing disorders (i.e., anxiety and mood disorders), in which self-related tasks were frequently used to investigate internalizing psychopathology. As one of the most frequently seen internalizing disorder in primary care, patients with generalized anxiety disorder (GAD) are characterized by inappropriate self-related processing such as negative self-referential thinking. However, relevant neural mechanisms remain unknown. In this study, participants underwent a self-related task which they were presented with several positive and negative trait words and were required to judge the extent to which these traits matched themselves when compared to their average peers. Aberrant brain activation and functional connectivity of GAD were detected during processing positive and negative traits. Compared to healthy controls (HCs), patients with GAD exhibited abnormal self-processing which manifested as lower biased self-rating scores particularly for negative traits and weaker brain activity in the left dorsomedial prefrontal cortex, inferior frontal gyrus, superior temporal sulcus (STS), and bilateral lingual gyrus when processing trait words. Abnormal functional connections between these hypoactive regions and regions associated with reward, emotion, and theory of mind were observed in subsequent psychophysiological interaction analysis. An attenuation of connectivity between the left insula and left STS was associated with greater severity of anxiety symptom in GAD patients. These findings provide insight into the abnormal neurocognitive mechanisms of biased self-related processing in GAD patients, which involves distorted self-schema accompanied by abnormal activation and functional connections of regions implicated in self-related and social cognition processing.
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http://dx.doi.org/10.1016/j.pnpbp.2022.110595DOI Listing
July 2022

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Drug Metab Dispos 2022 Jul 2. Epub 2022 Jul 2.

Pharmacokinetics Dynamics and Metabolism, Pfizer Inc, United States

Excess dietary fructose consumption promotes metabolic dysfunction thereby increasing the risk of obesity, type 2 diabetes, non-alcoholic steatohepatitis (NASH), and related comorbidities. PF-06835919, a first-in-class ketohexokinase (KHK) inhibitor, showed reversal of such metabolic disorders in preclinical models and clinical studies, and is under clinical development for the potential treatment of NASH. In this study, we evaluated the transport and metabolic pathways of PF-06835919 disposition and assessed pharmacokinetics in preclinical models. PF-06835919 showed active uptake in cultured primary human hepatocytes, and substrate activity to organic anion transporter (OAT)2 and organic anion transporting-polypeptide (OATP)1B1 in transfected cells. "SLC-phenotyping" studies in human hepatocytes suggested contribution of passive uptake, OAT2- and OATP1B-mediated transport to the overall uptake to be about 15%, 60% and 25%, respectively. PF-06835919 showed low intrinsic metabolic clearance in vitro, and was found to be metabolized via both oxidative pathways (58%) and acyl glucuronidation (42%) by CYP3A, CYP2C8, CYP2C9 and UGT2B7. Following intravenous dosing, PF-06835919 showed low clearance (0.4-1.3 mL/min/kg) and volume of distribution (0.17-0.38 L/kg) in rat, dog and monkey. Human oral pharmacokinetics are predicted within 20% error when considering transporter-enzyme interplay in a PBPK model. Finally, unbound liver-to-plasma ratio (Kp) measured in vitro using rat, NHP and human hepatocytes was found to be approximately 4, 25 and 10, respectively. Similarly, liver Kp in rat and monkey following intravenous dosing of PF-06835919 was found to be 2.5 and 15, respectively, and notably higher than the muscle and brain Kp, consistent with the active uptake mechanisms observed in vitro. This work characterizes the transport/metabolic pathways in the hepatic disposition of PF-06835919, a first-in-class KHK inhibitor for the treatment of metabolic disorders and NASH. Phenotyping studies using transfected systems, human hepatocytes and liver microsomes signifies the role of OAT2 and OATP1B1 in the hepatic uptake and multiple enzymes in the metabolism of PF-06835919. Data presented suggest hepatic transporter-enzyme interplay in determining its systemic concentrations and potential enrichment in liver, a target site for KHK inhibition.
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http://dx.doi.org/10.1124/dmd.122.000953DOI Listing
July 2022

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development.

Acta Pharm Sin B 2022 Jun 17;12(6):2751-2777. Epub 2022 Mar 17.

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.
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http://dx.doi.org/10.1016/j.apsb.2022.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214059PMC
June 2022

Diagnostic classification of cancers using DNA methylation of paracancerous tissues.

Sci Rep 2022 Jun 23;12(1):10646. Epub 2022 Jun 23.

Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

The potential role of DNA methylation from paracancerous tissues in cancer diagnosis has not been explored until now. In this study, we built classification models using well-known machine learning models based on DNA methylation profiles of paracancerous tissues. We evaluated our methods on nine cancer datasets collected from The Cancer Genome Atlas (TCGA) and utilized fivefold cross-validation to assess the performance of models. Additionally, we performed gene ontology (GO) enrichment analysis on the basis of the significant CpG sites selected by feature importance scores of XGBoost model, aiming to identify biological pathways involved in cancer progression. We also exploited the XGBoost algorithm to classify cancer types using DNA methylation profiles of paracancerous tissues in external validation datasets. Comparative experiments suggested that XGBoost achieved better predictive performance than the other four machine learning methods in predicting cancer stage. GO enrichment analysis revealed key pathways involved, highlighting the importance of paracancerous tissues in cancer progression. Furthermore, XGBoost model can accurately classify nine different cancers from TCGA, and the feature sets selected by XGBoost can also effectively predict seven cancer types on independent GEO datasets. This study provided new insights into cancer diagnosis from an epigenetic perspective and may facilitate the development of personalized diagnosis and treatment strategies.
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http://dx.doi.org/10.1038/s41598-022-14786-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226137PMC
June 2022

Ru-doping modulated cobalt phosphide nanoarrays as efficient electrocatalyst for hydrogen evolution rection.

J Colloid Interface Sci 2022 Nov 16;625:457-465. Epub 2022 Jun 16.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China. Electronic address:

Electrochemical water splitting is regarded as a prospective means for H production. The lack of efficient active sites and the sluggish kinetics in alkaline media remain the major obstacles for hydrogen evolution reaction (HER). Herein, a rational construction of Ru-doped cobalt phosphide leaf-like nanoarrays supported on carbon cloth (Ru-CoP NAs) was designed via a MOF-derived route and subsequent phosphating treatment for accelerating HER in the alkaline. The unique hierarchical structure is conductive to exposing more active sites and accelerating the diffusion of electrolyte and the release of H bubble. The optimized Ru-CoP-2.5 NAs exhibits a small overpotential of 52 mV to drive 10 mA cm for HER and a low Tafel slope of 39.7 mV dec in 1 M KOH, which outperforms most of other reported CoP-based electrocatalysts. Furthermore, density functional theory (DFT) calculations unveil that Ru dopants can modulate the electron environment around pure CoP and optimize the adsorption energy of H*, accelerating the reaction kinetics. This work provides an insight to promote the electrocatalytic activity of metal phosphide for hydrogen production.
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http://dx.doi.org/10.1016/j.jcis.2022.06.059DOI Listing
November 2022

Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice.

Chem Sci 2022 Jun 2;13(21):6303-6308. Epub 2022 May 2.

School of Chemistry and Molecular Engineering, East China Normal University 200241 Shanghai China

Phase separation in cell membranes promotes the assembly of transmembrane receptors to initiate signal transduction in response to environmental cues. Many cellular behaviors are manipulated by promoting membrane phase separation through binding to multivalent extracellular ligands. However, available extracellular molecule tools that enable manipulating the clustering of transmembrane receptors in a controllable manner are rare. In the present study, we report a DNA nanodevice that enhances membrane phase separation through the clustering of dynamic lipid rafts. This DNA nanodevice is anchored in the lipid raft region of the cell membrane and initiated by ATP. In a tumor microenvironment, this device could be activated to form a long DNA duplex on the cell membrane, which not only enhances membrane phase separation, but also blocks the interaction between the transmembrane surface adhesion receptor and extracellular matrix, leading to reduced migration. We demonstrate that the ATP-activated DNA nanodevice could inhibit cancer cell migration both and . The concept of using DNA to regulate membrane phase separation provides new possibilities for manipulating versatile cell functions through rational design of functional DNA structures.
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http://dx.doi.org/10.1039/d2sc00371fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159096PMC
June 2022

Single Particle Hopping as an Indicator for Evaluating Electrocatalysts.

Nano Lett 2022 07 21;22(13):5495-5502. Epub 2022 Jun 21.

Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 10084, China.

The design and screening of electrocatalysts for gas evolution reactions suffer from little understanding of multiphase processes at the electrode-electrolyte interface. Due to the complexity of the multiphase interface, it is still a great challenge to capture gas evolution dynamics under operando conditions to precisely portray the intrinsic catalytic performance of the interface. Here, we establish a single particle imaging method to real-time monitor a potential-dependent vertical motion or hopping of electrocatalysts induced by electrogenerated gas nanobubbles. The hopping feature of a single particle is closely correlated with intrinsic activities of electrocatalysts and thus is developed as an indicator to evaluate gas evolution performance of various electrocatalysts. This optical indicator diminishes interference from heterogeneous morphologies, non-Faradaic processes, and parasitic side reactions that are unavoidable in conventional electrochemical measurements, therefore enabling precise evaluation and high-throughput screening of catalysts for gas evolution systems.
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http://dx.doi.org/10.1021/acs.nanolett.2c01631DOI Listing
July 2022

Gonadal hormone trigger the dynamic microglial alterations through Traf6/TAK1 axis that correlate with depressive behaviors.

J Psychiatr Res 2022 Aug 14;152:128-138. Epub 2022 Jun 14.

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Gonadal hormone deficiency is associated with the development of depression, but what mediates this association is unclear. To test the possibility that it reflects neuroimmune and neuroinflammatory processes, we analyzed how gonadal hormone deficiency and replacement affect microglial activation and inflammatory response during the development of depressive symptomatology in gonadectomized male mice. Testosterone level and the ratio of testosterone to estradiol in the serum and brain tissue of mice exposed to 3-35 days of chronic unpredictable stress were much lower than in control animals. Gonadal hormone sustained deficiency in gonadectomized mice and subsequent led to acute inflammation at day 7 following castration. Activating microglia in mice exposed to 7 days of castration subsequently suppressed the proliferation of microglia, such that their numbers in hippocampus and cortex were lower than the numbers in sham-operated mice after 30 days of castration. Here, we showed that gonadal hormone deficiency induces Traf6-mediated microglia activation, a type of inflammatory mediator. Microglia treated in this way for long time showed down-regulation of activation markers, abnormal morphology and depressive-like behaviors. Restoration and maintenance of a fixed ratio of testosterone to estradiol significantly suppressed microglial activation, neuronal necroptosis, dramatically inducing hippocampal neurogenesis and reducing depressive behaviors via the suppression of Traf6/TAK1 pathway. These findings suggest that activated or immunoreactive microglia contribute to gonadal hormone deficiency-induced depression, as well as testosterone and estradiol exert synergistic anti-depressant effects via suppressing microglial activaton in gonadectomized male mice, possibly through Traf6 signaling.
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http://dx.doi.org/10.1016/j.jpsychires.2022.06.026DOI Listing
August 2022

Rapid High-Throughput Assay Identified Gemcitabine and Derivatives As Potent Inhibitors Against Multidrug-Resistant .

Assay Drug Dev Technol 2022 May-Jun;20(4):175-182

College of Pharmaceutical Science, Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.

Staphylococcus aureus (MRSA) are challenging pathogenic bacteria that can cause severe infection leading to high mortality rates. We found that both the oxacillin- and cefoxitin-resistant strains isolated from clinic showed multidrug-resistant (MDR) characteristics. Through rapid high-throughput screen (HTS) of a compound library, gemcitabine and selen compounds were found to effectively inhibit growth. For further improvement, we synthesized selen-containing gemcitabine that demonstrated relatively potent antimicrobial activity against several MDR MRSA . The HTS assay and gemcitabine selen derivative provided a useful tool to explore an effective molecular target to treat MDR MRSA.
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http://dx.doi.org/10.1089/adt.2022.034DOI Listing
June 2022

Metal-Organic Framework-Derived Three-Dimensional Macropore Nitrogen-Doped Carbon Frameworks Decorated with Ultrafine Ru-Based Nanoparticles for Overall Water Splitting.

Inorg Chem 2022 Jun 14;61(25):9685-9692. Epub 2022 Jun 14.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China.

Hydrogen energy with the advantages of green, sustainability, and high energy density has been considered as an alternative to fossil fuel energy. Water electrolysis to produce hydrogen is a promising energy conversion technology but limited to the large overpotential; thus, a highly efficient electrocatalyst is urgently needed. Herein, Ru-based electrocatalysts including an ultrathin Ru/three-dimensional (3D) macropore N-doped carbon framework (Ru/3DMNC) and ultrathin RuO/3D macropore N-doped carbon framework (RuO/3DMNC) are first prepared using a Zn-centered metal-organic framework (MOF, ZIF-8) as the precursor. The ultrathin 3D macropore framework structure together with N doping endows the as-synthesized Ru-based electrocatalysts with abundant exposed catalytic active sites, good electroconductivity, and excellent electron/mass transport, accomplishing improved activities for hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. The Ru/3DMNC and RuO/3DMNC present low overpotentials of 50.96 and 216.74 mV to reach a current density of 10 mA cm. Moreover, the overall water splitting device constructed by Ru/3DMNC and RuO/3DMNC as the cathode and anode catalysts, respectively, affords a current density of 10 mA cm only at 1.51 V, which is superior to the Pt/C||RuO cell (1.573 V). This work provides a rational strategy to design and construct the efficient framework structure electrocatalysts for water splitting using MOFs as the precursor.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01151DOI Listing
June 2022

An acetylated mannan isolated from Aloe vera induce colorectal cancer cells apoptosis via mitochondrial pathway.

Carbohydr Polym 2022 Sep 8;291:119464. Epub 2022 Apr 8.

Department of R&D, Biotech&Science Company of UP, Ltd., 918 Guangzhou Avenue, Guangzhou, Guangdong 510000, China. Electronic address:

The anti-cancer effects of Aloe vera barbadensis extract C (AVBEC) have been demonstrated in a previous study. However, the specific functional ingredient and mechanism remain undefined. This study aimed to evaluate the function and associated mechanisms of purified polysaccharide (ABPA1) from AVBEC on colorectal cancer. Here, we identify that ABPA1 can induce colorectal cancer apoptosis. In vivo, ABPA1 significantly suppressed tumor growth in an orthotopic colon cancer model. Mechanistically, ABPA1 alters mitochondrial membrane permeability by promoting Bax translocation while causing cytochrome-c release, which initiates the caspase cascade reaction. Additionally, we found that ABPA1 exerted distinct impacts on the mitochondrial metabolism of colorectal cancer cells. Our study elucidated the mechanism by which the polysaccharide ABPA1 induces apoptosis in colorectal cancer cells through the regulation of Bax and cytochrome-c mediated mitochondrial pathway, indicating that ABPA1 may be developed as a mitochondrial-targeting anti-cancer drug.
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http://dx.doi.org/10.1016/j.carbpol.2022.119464DOI Listing
September 2022

Novel Small Molecule Tyrosine Kinase 2 Pseudokinase Ligands Block Cytokine-Induced TYK2-Mediated Signaling Pathways.

Front Immunol 2022 20;13:884399. Epub 2022 May 20.

R & D Center, Shanghai Hengrui Pharmaceutical Co. Ltd., Shanghai, China.

A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, and inflammatory bowel disease). Thus, TYK2 represents an attractive target to develop small-molecule therapeutics for the treatment of cytokine-driven inflammatory diseases. Selective inhibition of TYK2 over other JAK isoforms is critical to achieve a favorable therapeutic index in the development of TYK2 inhibitors. However, designing small molecule inhibitors to target the adenosine triphosphate (ATP) binding site of TYK2 kinase has been challenging due to the substantial structural homology of the JAK family catalytic domains. Here, we employed an approach to target the JAK homology 2 (JH2) pseudokinase regulatory domain of the TYK2 protein. We developed a series of small-molecule TYK2 pseudokinase ligands, which suppress the TYK2 catalytic activity through allosteric regulation. The TYK2 pseudokinase-binding small molecules in this study simultaneously achieve high affinity-binding for the TYK2 JH2 domain while also affording significantly reduced affinity for the TYK2 JAK homology 1 (JH1) kinase domain. These TYK2 JH2 selective molecules, although possessing little effect on suppressing the catalytic activity of the isolated TYK2 JH1 catalytic domain in the kinase assays, can still significantly block the TYK2-mediated receptor-stimulated pathways by binding to the TYK2 JH2 domain and allosterically regulating the TYK2 JH1 kinase. These compounds are potent towards human T-cell lines and primary immune cells as well as in human whole-blood specimens. Moreover, TYK2 JH2-binding ligands exhibit remarkable selectivity of TYK2 over JAK isoforms not only biochemically but also in a panel of receptor-stimulated JAK1/JAK2/JAK3-driven cellular functional assays. In addition, the TYK2 JH2-targeting ligands also demonstrate high selectivity in a multi-kinase screening panel. The data in the current study underscores that the TYK2 JH2 pseudokinase is a promising therapeutic target for achieving a high degree of biological selectivity. Meanwhile, targeting the JH2 domain represents an appealing strategy for the development of clinically well-tolerated TYK2 inhibitors that would have superior efficacy and a favorable safety profile compared to the existing Janus kinase inhibitors against autoimmune diseases.
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http://dx.doi.org/10.3389/fimmu.2022.884399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186491PMC
June 2022

Observation of Ultrafast Interfacial Exciton Formation and Relaxation in Graphene/MoS Heterostructure.

J Phys Chem Lett 2022 Jun 3:5123-5130. Epub 2022 Jun 3.

Department of Physics, Shanghai University, Shanghai 200444, China.

Heterostructures constructed from graphene and transition metal dichalcogenides (TMDs) have established a new platform for optoelectronic applications. After a large number of studies, one intriguing debate is the existence of the interfacial exciton in graphene/TMDs. Hereby, by combined optical pump-terahertz probe spectroscopy and transient absorption spectroscopy, we report the observation of the interfacial exciton in graphene/MoS heterostructure. With the photon energy well below the band gap of monolayer MoS, the hot electrons of graphene are transferred to MoS within 0.5 ps; subsequently, the relaxation of the holes in graphene and electrons in MoS shows an identical time scale of 15-18 ps, which manifests the formation and relaxation of the interfacial exciton in the heterostructure following photoexcitation. Moreover, a model of the carrier heating and photogating effect in graphene is proposed to estimate the amount of transferred charge, which agrees well with the experimental results. Our study provides insights into the dynamics of graphene-based heterostructure interfacial non-equilibrium carriers.
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http://dx.doi.org/10.1021/acs.jpclett.2c01197DOI Listing
June 2022

LncRNA SNHG15 Modulates Ischemia-Reperfusion Injury in Human AC16 Cardiomyocytes Depending on the Regulation of the miR-335-3p/TLR4/NF-κB Pathway.

Int Heart J 2022 ;63(3):578-590

Department of Cardiology, Yibin Second People's Hospital.

Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
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http://dx.doi.org/10.1536/ihj.21-511DOI Listing
June 2022

Early Drug-Induced Liver Injury Risk Screening: "Free," as Good as It Gets.

Toxicol Sci 2022 Jul;188(2):208-218

Drug Safety Research & Development, Pfizer Worldwide Research, Development and Medical, Groton, Connecticut 06340, USA.

For all the promise of and need for clinical drug-induced liver injury (DILI) risk screening systems, demonstrating the predictive value of these systems versus readily available physicochemical properties and inherent dosing information has not been thoroughly evaluated. Therefore, we utilized a systematic approach to evaluate the predictive value of in vitro safety assays including bile salt export pump transporter inhibition and cytotoxicity in HepG2 and transformed human liver epithelial along with physicochemical properties. We also evaluated the predictive value of in vitro ADME assays including hepatic partition coefficient (Kp) and its unbound counterpart because they provide insight on hepatic accumulation potential. The datasets comprised of 569 marketed drugs with FDA DILIrank annotation (most vs less/none), dose and physicochemical information, 384 drugs with Kp and plasma protein binding data, and 279 drugs with safety assay data. For each dataset and combination of input parameters, we developed random forest machine learning models and measured model performance using the receiver operator characteristic area under the curve (ROC AUC). The median ROC AUC across the various data and parameters sets ranged from 0.67 to 0.77 with little evidence of additive predictivity when including safety or ADME assay data. Subsequent machine learning models consistently demonstrated daily dose, fraction sp3 or ionization, and cLogP/D inputs produced the best, simplest model for predicting clinical DILI risk with an ROC AUC of 0.75. This systematic framework should be used for future assay predictive value assessments and highlights the need for continued improvements to clinical DILI risk annotation.
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http://dx.doi.org/10.1093/toxsci/kfac054DOI Listing
July 2022

Carbon vacancy-mediated exciton dissociation in TiCT/g-CN Schottky junctions for efficient photoreduction of CO.

J Colloid Interface Sci 2022 Oct 15;623:487-499. Epub 2022 May 15.

School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China. Electronic address:

Earth-abundant g-CN is a promising photocatalyst for CO reduction, but its practical application is severely limited by the excitonic effect of g-CN derived from strong binding energy and lack of electron-enriched active sites. Herein, we design a novel 2D/2D Schottky junction photocatalysts comprising of TiCT-modified defective g-CN nanosheets with carbon vacancy (denoted as TiCT/V-CN) by a self-assembly method. The carbon vacancies in g-CN promote exciton dissociation into free charge, while the formed Schottky junctions between TiCT and V-CN further enables a directional charge transfer, thus providing an electron-rich catalytic surface for the CO reduction. Thanks to the synergy of promoted exciton dissociation and directional electron transfer, the optimal 20% TiCT/V-CN display a high CO evolution rate of 20.54 µmol·g·h under visible light irradiation, which is 7.4 times higher than that of bare CN. This work highlights the synergy of the promoted exciton dissociation and directional electron transfer in the activity enhancement of photocatalytic CO reduction.
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http://dx.doi.org/10.1016/j.jcis.2022.05.064DOI Listing
October 2022

SHR1032, a novel STING agonist, stimulates anti-tumor immunity and directly induces AML apoptosis.

Sci Rep 2022 05 20;12(1):8579. Epub 2022 May 20.

Shanghai Hengrui Pharmaceutical Co. Ltd., 279 Wenjing Road, Shanghai, 200245, China.

Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation and the adaptive immune responses against tumor. The first-generation of STING agonists, cyclic di-nucleotide (CDN), mimicked the endogenous STING ligand cyclic guanosine monophosphate adenosine monophosphate, and displayed limited clinical efficacy. Here we report the discovery of SHR1032, a novel small molecule non-CDN STING agonist. Compared to the clinical CDN STING agonist ADU-S100, SHR1032 has much higher activity in human cells with different STING haplotypes and robustly induces interferon β (IFNβ) production. When dosed intratumorally, SHR1032 induced strong anti-tumor effects in the MC38 murine syngeneic tumor model. Pharmacodynamic studies showed induction of IFNβ, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in the tumors and, to a lower extent, in the plasma. More importantly, we found SHR1032 directly causes cell death in acute myeloid leukemia (AML) cells. In conclusion, our findings demonstrate that in addition to their established ability to boost anti-tumor immune responses, STING agonists can directly eradicate AML cells, and SHR1032 may present a new and promising therapeutic agent for cancer patients.
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http://dx.doi.org/10.1038/s41598-022-12449-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122897PMC
May 2022

Synergistically Coupled CoMo/CoMoP Electrocatalyst for Highly Efficient and Stable Overall Water Splitting.

Inorg Chem 2022 May 17;61(21):8328-8338. Epub 2022 May 17.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, P. R. China.

Finding reservoir-rich and efficient bifunctional electrocatalysts for water splitting is key to further sustainable energy development. Transition metal phosphides (TMPs) are extensively exploited as effective electrocatalysts, but the construction of strong coupling interfaces to improve catalytic performance by simple methods is still a bottleneck. Here, we designed and prepared a novel heterostructure electrocatalyst composed of cobalt-molybdenum (CoMo) alloy particles integrated with CoMoP nanosheets via the method of template-assisted conversion, followed by electrodeposition. Thanks to the strong interfacial coupling and synergistic effect between CoMo alloy particles and CoMoP nanosheets, the prepared CoMo/CoMoP/NF shows outstanding activity with overpotentials of only 29 mV for the hydrogen evolution reaction (HER) and 246 mV for the oxygen evolution reaction (OER) in 1 M KOH at a current density of 10 mA cm. Furthermore, the assembled CoMo/CoMoP || CoMo/CoMoP electrode can attain 10 mA cm with a low battery voltage of 1.54 V. This study offers a valuable reference to the construction of bimetallic alloy/bimetallic phosphide heterostructure electrocatalysts, which applies to the large-scale application of electrocatalytic energy conversion technology.
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http://dx.doi.org/10.1021/acs.inorgchem.2c00923DOI Listing
May 2022

Loss of superiority illusion in bipolar depressive disorder: A combined functional and structural MRI study.

J Psychiatr Res 2022 07 28;151:391-398. Epub 2022 Apr 28.

The Clinical Hospital of Chengdu Brain Science Institute, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; The Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

Superiority illusion (SI) is a positive cognitive bias related to self, manifested as overestimated self-appraisal. Negative self-schema is a core feature of the cognitive model of depression, including bipolar depressive disorder (BDD). However, only little research has explored the impaired self-processing in BDD. The potential alteration of positive self-bias and the corresponding neural mechanism in BDD remains unclear. This study aimed to investigate the underlying neural mechanism of self-processing in BDD combining task-related functional magnetic resonance imaging and high-resolution T1 structural imaging. Forty-three BDD and forty-eight healthy controls were recruited and underwent a self-related task, where participants were required to evaluate how they compared with their average peers on a serial of positive and negative traits. We defined the ratio of neural activation and gray matter volume (GMV) in a region as the functional-structural coupling index to detect the changes of brain image in BDD. Furthermore, we used moderation analysis to explore the relationship among functional-structural coupling, behavioral scores and depression symptoms. BDD exhibited decreased task activation, GMV, and functional-structural coupling in bilateral anterior insula (AI) and inferior parietal lobule (IPL). The associations between functional-structural coupling in the right AI, IPL and negative trait self-rating scores were moderated by depressive symptom severity. The study revealed disturbed self-related processing and provided new evidences to neuropsychological dysfunction in BDD.
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http://dx.doi.org/10.1016/j.jpsychires.2022.04.034DOI Listing
July 2022
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