Publications by authors named "Tian Zhang"

935 Publications

Retrospective Study of Effects of Preoperative BMI on Early Outcomes in Recipients After Kidney Transplant.

Transplant Proc 2022 Aug 4. Epub 2022 Aug 4.

Division of Life Sciences and Medicine, Department of Nursing, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China. Electronic address:

Background: The objective of this retrospective study was to establish the effect of the preoperative body mass index (BMI) on early outcomes of recipients after a kidney transplant, including liver and kidney function and fasting blood glucose recovery.

Methods: Our analytical cohort were patients who had undergone a kidney transplant at The First Affiliated Hospital of USTC [2016-2019]. The BMI classifications were underweight (<18.5 kg/m), normal weight (18.5-23.9 kg/m), and overweight or obese (≥24 kg/m). A χ test was conducted to compare differences between the patients in the different BMI groups.

Results: We enrolled 831 recipients in the study. The percentage of patients with normal serum creatinine and normal urea nitrogen in the BMI ≥24 group was lower at different periods after surgery (P<0.05). The percentage of patients with normal uric acid in the normal weight group was higher on day 1 and the first week after surgery (P < 0.001). In the first and second weeks postsurgery, the percentage of patients with aspartate transaminase/alanine aminotransaminase in the BMI ≥24 group was lower (P < .005). In the first week postsurgery, the percentage of patients with normal albumin/globulin in the normal weight group was higher (P < .05). No statistically significant difference among the 3 groups was found in the incidence of hyperglycemia (P > .05).

Conclusions: The patients who were overweight or obese preoperatively had poorer renal and liver functions postoperatively. Targeted interventions to control or mitigate rates of overweight or obesity preoperatively should be identified.
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http://dx.doi.org/10.1016/j.transproceed.2022.04.030DOI Listing
August 2022

Clarifying winter clean heating importance: Insight chemical compositions and cytotoxicity exposure to primary and aged pollution emissions in China rural areas.

J Environ Manage 2022 Aug 4;320:115822. Epub 2022 Aug 4.

Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address:

Residential solid fuel combustion (RSFC) is an important source of PM. Here we investigate the cytotoxicity of primarily emitted and photochemically aged PM to A549 cells. Owing to the formation of water-soluble ions and organics (e.g., oPAHs and nPAHs), emission factors of PM were increased by 44.4% on average after 7-day equivalent photochemical aging, which greatly altered chemical profiles of freshly emitted PM. Consequently, the cytotoxicity varied with aging duration that 2-day and 7-day aged PM induced 22.5% and 35.1%, respectively, higher levels of reactive oxygen species than primary emissions. Similar increases were also observed for multi-cytotoxicity. Correlation analysis and western blot results collectively confirmed HO-1/Nrf-2 signaling pathway dominated the cytotoxicity of aged PM from RSFC, which was regulated by the enhanced o-PAHs and n-PAHs during photochemical aging. Thus, aged and secondary aerosol exposure needs to be paid more attention due to the enhanced cytotoxicity and the vast crowd involved.
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http://dx.doi.org/10.1016/j.jenvman.2022.115822DOI Listing
August 2022

Roll-to-roll Fabrication of Zero-Volume-Expansion Lithium Composite Anodes to Realize High-Energy-Density Flexible and Stable Lithium Metal Batteries.

Adv Mater 2022 Aug 3:e2205677. Epub 2022 Aug 3.

Department of Materials Science and Engineering, Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Solid-State Batteries, Southern University of Science and Technology, Shenzhen, 518055, China.

Lithium (Li) metal anode offers a promising solution for high-energy-density lithium metal batteries (LMBs). However, the significant volume expansion of Li metal during charge results in poor cycling stability as a result of the dendritic deposition and broken solid electrolyte interphase. Herein, we propose a facile one-step roll-to-roll fabrication of a zero-volume-expansion Li metal composite anode (zeroVE-Li) to realize the outstanding electrochemical and mechanical stability of high-energy-density LMBs. The zeroVE-Li possesses a sandwich-like trilayer structure, which consists of an upper electron-insulating layer and a bottom lithiophilic layer that synergistically guides the Li deposition from the bottom up, and a middle porous layer that eliminates the volume expansion. This sandwich structure eliminates dendrite formation, prevents volume change during cycling, and provides outstanding flexibility to the Li metal anode even at a practical areal capacity over 3.0 mAh cm . Pairing zeroVE-Li with commercial NMC or LCO cathode, we demonstrate flexible LMBs that offer a record-breaking Figure of Merit (FOM, 45.6), large whole-cell energy density (375 Wh L , based on the volume of the anode, separator, cathode, and package), high-capacity retention (>99.8% per cycle), and remarkable mechanical robustness under practical conditions. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202205677DOI Listing
August 2022

Ethical implications of early genetic diagnosis in an infant with Lesch-Nyhan syndrome.

J Genet Couns 2022 Aug 2. Epub 2022 Aug 2.

Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Pathogenic variants in HPRT1 lead to deficiency in hypoxanthine-guanine phosphoribosyltransferase and are responsible for a spectrum of disorders. The severe phenotype is termed Lesch-Nyhan syndrome (LNS) and is inherited in an X-linked recessive manner. Most individuals with LNS have profound intellectual and physical disabilities throughout life including self-mutilating behaviors. Here, we present the case of a male infant who was diagnosed with LNS at 3 weeks of age via rapid exome sequencing (ES), which revealed a hemizygous maternally inherited deletion of at least 1.3 Mb of Xq26.3, including exons 2 to 9 of HPRT1. We discuss the critical time points leading to this diagnosis while highlighting his parents' values that guided the decision-making. Genetic testing provided an early diagnosis for this infant that led to important considerations regarding goals of care in addition to raising new ethical concerns. This highlights the important role that early and rapid diagnostic genetic testing can play in helping families make difficult decisions. Additionally, this case highlights the complexity of discussing rare genetic diagnoses with families and facilitating critical discussions to empower the family toward making an informed decision.
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http://dx.doi.org/10.1002/jgc4.1616DOI Listing
August 2022

A two-stage process for the autotrophic and mixotrophic conversion of C1 gases into bacterial cellulose.

Bioresour Technol 2022 Jul 27;361:127711. Epub 2022 Jul 27.

School of Chemistry, Chemical Engineering, and Life Science, Wuhan University of Technology, Wuhan 430070, PR China; Shaoxing Institute for Advanced Research, Wuhan University of Technology, Shaoxing 312300, PR China.

Gas fermentation is a well-established process for the conversion of greenhouse gases from industrial wastes into valuable multi-carbon chemicals. Here, a two-stage process was developed to expand the product range of gas fermentation and synthesized the versatile biopolymer bacterial cellulose (BC). In the first stage, the acetogen Clostridium autoethanogenum was cultivated with H:CO:CO and produced ethanol and acetate. In the second stage, BC-synthesizing Komagataeibacter sucrofermentans was grown in the spent medium from gas fermentation. K. sucrofermentans was able to produce BC autotrophically from gas-derived metabolites alone as well as mixotrophically with the addition of exogenous glucose. In these circumstances, 1.31 g/L BC was synthesized with a major energetic contribution from C1 gas fermentation products. Mixotrophic BC characterization reveals unique properties including augmented mechanical strength, porosity, and crystallinity. This proof-of-concept process demonstrates that BC can be produced from gases and holds good potential for the efficient conversion of C1 wastes.
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http://dx.doi.org/10.1016/j.biortech.2022.127711DOI Listing
July 2022

Facile Access to Far-Red Fluorescent Probes with Through-Space Charge Transfer Effect for In Vivo Two-Photon Microscopy of Mouse Cerebrovascular System.

Angew Chem Int Ed Engl 2022 Jul 28. Epub 2022 Jul 28.

The Chinese University of Hong Kong, Shenzhen, School of Science and Engineering, 2001 Longxiang Boulevard, Longgang District, 518172, Shenzhen, CHINA.

Many efforts have been devoted to obtain fluorescent probes via synthetic approaches. In this communication, we developed a facile strategy to construct far-red fluorescent probes based on the through-space charge transfer of the acceptors with the donors in the complexes and their "twist + twist" interactions. Due to their rare two-photon excitation property, we for the first time presented their utility in in vivo imaging of mouse cerebrovascular system.
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http://dx.doi.org/10.1002/anie.202209590DOI Listing
July 2022

Oral anticancer agent (OAA) adherence and survival in elderly patients with metastatic renal cell carcinoma (mRCC).

Urology 2022 Jul 22. Epub 2022 Jul 22.

Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, NC; Lineberger Comprehensive Cancer Center, UNC-CH, Chapel Hill, NC.

Objective: To examine real-world adherence to oral anticancer agents (OAAs) and its association with outcomes among Medicare beneficiaries with metastatic renal cell carcinoma (mRCC).

Methods: SEER-Medicare retrospective cohort study of patients with metastatic renal cell carcinoma (mRCC) who received an OAA between 2007 and 2015. We examined A) adherence and B) overall and disease-specific two-year survival landmarked at 3 months after OAA initiation. Adherence was assessed by calculating the proportion of days covered (PDC) within 3 months of OAA initiation, with adherent use being defined as PDC > 80%.

Results: A total of 905 patients met study criteria, of whom 445 patients (49.2%) were categorized as adherent to initial OAA treatment. Adjusting for clinical and demographic factors revealed decreased odds of adherence associated with living within an impoverished neighborhood (OR 0.49, CI 0.0.33 - 0.74) and out-of-pocket costs > $200 (OR 0.68, CI 0.47-.98). Adherence was associated with improved two-year survival in univariate analysis (logrank test, p = 0.01) and a non-significant trend towards an association with decreased all-cause (HR 0.87, CI 0.72 - 1.05) and RCC-specific survival (HR 0.84, CI 0.69 - 1.03) in multivariable analysis.

Conclusions: Local poverty levels and high out-of-pocket costs are associated with poor initial adherence to OAA therapy in Medicare beneficiaries with mRCC, which in turn, suggests a trend towards poor overall and disease-specific survival. Efforts to improve outcomes in the broader mRCC population should incorporate OAA adherence and economic factors.
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http://dx.doi.org/10.1016/j.urology.2022.07.012DOI Listing
July 2022

Recent advances in the breakdown of microplastics: strategies and future prospectives.

Environ Sci Pollut Res Int 2022 Jul 25. Epub 2022 Jul 25.

School of Energy and Environmental Engineering, University of Science & Technology Beijing, Beijing, 100083, People's Republic of China.

Microplastics pollution is becoming a major environmental issue, and exposure to microplastics has been associated with numerous adverse results to both the ecological system and humans. This work summarized the state-of-the-art developments in the breakdown of microplastics, including natural weathering, catalysts-assisted breakdown and biodegradation. Characterization techniques for microplastic breakdown involve scanning electron microscopy, Fourier infrared spectroscopy, X-ray photoelectron spectroscopy, etc. Bioavailability and adsorption capacity of microplastics may change after they are broken down, therefore leading to variety in microplastics toxicity. Further prospectives for should be focused on the determination and toxicity evaluation of microplastics breakdown products, as well as unraveling uncultivable microplastics degraders via cultivation-independent approaches. This work benefits researchers interested in environmental studies, particularly the removal of microplastics from environmental matrix.
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http://dx.doi.org/10.1007/s11356-022-22004-0DOI Listing
July 2022

Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity.

Acta Pharm Sin B 2022 Jul 26;12(7):3139-3155. Epub 2022 Feb 26.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (PD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.
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http://dx.doi.org/10.1016/j.apsb.2022.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293721PMC
July 2022

Impact of Mobile Game Addiction Tendency on Chinese University Students: A Hierarchical Linear Modeling Study.

Front Psychol 2022 4;13:937446. Epub 2022 Jul 4.

Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, China.

This study used hierarchical linear modeling (HLM) to investigate the differences in mobile game addiction tendencies among universities (i.e., double first-class universities, ordinary colleges and universities, and higher vocational colleges), and to examine the influencing factors of mobile game addiction tendency at the individual and university levels. The participants of this study were 4,024 college students who completed the Chinese Mobile Phone Game Addiction Scale, UCLA Loneliness Scale, and Positive and Negative Affect Scale. Loneliness ( = 0.052), positive emotions ( = -0.126), negative emotions ( = 0.232), and double first-class universities ( = 0.368) significantly predicted mobile game addiction tendencies. A significant cross-level interaction between double first-class universities and other factors (i.e., positive emotions, negative emotions, and mobile game addiction) was observed. The novelty of this study is that it distinguishes the various effects of mobile phone addiction tendency at the individual and university levels.
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http://dx.doi.org/10.3389/fpsyg.2022.937446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291722PMC
July 2022

Image-guided/improved diseases management: From immune-strategies and beyond.

Adv Drug Deliv Rev 2022 Jul 9;188:114446. Epub 2022 Jul 9.

Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China; University of Chinese Academy of Sciences. Beijing 100049, China. Electronic address:

Timely and accurate assessment and diagnosis are extremely important and beneficial for all diseases, especially for some of the major human disease, such as cancers, cardiovascular diseases, infectious diseases, and neurodegenerative diseases. Limited by the variable disease microenvironment, early imperceptible symptoms, complex immune system interactions, and delayed clinical phenotypes, disease diagnosis and treatment are difficult in most cases. Molecular imaging (MI) techniques can track therapeutic drugs and disease sites in vivo and in vitro in a non-invasive, real-time and visible strategies. Comprehensive visual imaging and quantitative analysis based on different levels can help to clarify the disease process, pathogenesis, drug pharmacokinetics, and further evaluate the therapeutic effects. This review summarizes the application of different MI techniques in the diagnosis and treatment of these major human diseases. It is hoped to shed a light on the development of related technologies and fields.
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http://dx.doi.org/10.1016/j.addr.2022.114446DOI Listing
July 2022

Facts and hopes for immunotherapy in renal cell carcinoma.

Clin Cancer Res 2022 Jul 12. Epub 2022 Jul 12.

The University of Texas Southwestern Medical Center, Dallas, Texas, United States.

Immunotherapy has made a significant impact in many solid tumors, including renal cell carcinoma (RCC). RCC has been known to be immune responsive since the cytokine era of interferon-alfa and interleukin-2, but only a small number of patients had durable clinical benefit. Since then, discoveries of key tumor drivers, as well as an understanding of the contribution of angiogenesis and the tumor microenvironment (TME), has led to advances in drug development ultimately transforming patient outcomes. Combinations of anti-angiogenic agents with immune checkpoint inhibitors are now standard of care. Current challenges include patient selection for immunotherapy combinations, resistance acquisition and optimally sequencing therapies. Discoveries about RCC biology, the TME and resistance mechanisms will likely pave the way for the next generation of therapies.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2372DOI Listing
July 2022

Effects of different silicate minerals on silicon activation by Ochrobactium sp. T-07-B.

Environ Sci Pollut Res Int 2022 Jul 9. Epub 2022 Jul 9.

Civil & Environmental Engineering Department, College of Engineering, University of Nebraska-Lincoln, Omaha, NE, 68182, USA.

As a kind of solid waste with a high silicon content, electrolytic manganese residue (EMR) can be utilized as silicon source by plants through bioleaching processes. EMR contains a variety of silicate minerals. In order to determine the source of available silicon in the bioleaching process of EMR, it is necessary to investigate the influence of silicate minerals in EMR on silicon-activating behavior of specific minerals. In this study, Ochrobactium sp. T-07-B was used to conduct bioleaching experiments on five kinds of silicate minerals with different structures (quartz, muscovite, biotite, olivine, and rhodonite); the growth of Ochrobactium sp. T-07-B, their acid- and polysaccharide-producing capacity, and evolution of surface morphology and structure of the silicate minerals in different systems were determined, so as to explore the silicon-activating capacity of Ochrobactium sp. T-07-B and the selectivity toward different minerals in the bioleaching process. Results showed that the effects of Ochrobactium sp. T-07-B for different silicate minerals were obviously different, and the sequence of silicon-activating efficiency from high to low was as follows: muscovite (65.84 mg·L) > biotite (63.84 mg·L) > olivine (55.76 mg·L) > rhodonite (50.98 mg·L) > quartz (23.63 mg·L). Results of this study may be of guiding significance for the future research on the silicon-activating behavior of solid waste.
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http://dx.doi.org/10.1007/s11356-022-21824-4DOI Listing
July 2022

Photoactivatable Silencing Extracellular Vesicle (PASEV) Sensitizes Cancer Immunotherapy.

Adv Mater 2022 Jul 6:e2204765. Epub 2022 Jul 6.

Advanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology (Institute of Engineering Medicine), Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Immunotherapy has delivered impressive outcomes in combating tumor malignancies. However, insufficient immune infiltration and poor immunogenicity within the tumor microenvironment (TME) greatly compromise patient response rates. Here, a photoactivatable silencing extracellular vesicle (PASEV) is developed for sensitized cancer immunotherapy. p21-Activated kinase 4 (PAK4) is a newly identified tumor-cell-intrinsic "guard" associated with immune exclusion. Small interfering RNA against PAK4 (siPAK4) is designed and assembled with a photoactivatable reactive-oxygen-species (ROS)-sensitive polymer to form the nanocomplex core, which is further camouflaged by extracellular vesicles from M1 macrophages. The PASEV not only serves as a vehicle for packaging, tumor accumulation, and ROS-responsive release of siPAK4 for potent PAK4 silencing, but also primes the TME through immunogenic phototherapy, thereby simultaneously boosting intratumoral infiltration and immune activation. The combined immunotherapy elicits robust anticancer immunity, thus showing great promise for fighting cancers. This work opens a new avenue to simultaneously boost intratumoral infiltration and immune activation for sensitized cancer immunotherapy.
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http://dx.doi.org/10.1002/adma.202204765DOI Listing
July 2022

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery in patients with locally advanced esophageal squamous cell carcinoma who achieved clinical complete response when induction chemoradiation finished: A phase II random.

Radiother Oncol 2022 Jun 25;174:1-7. Epub 2022 Jun 25.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, China. Electronic address:

Background And Purpose: More than 40% of patients with esophageal squamous cell carcinoma (ESCC) exhibit pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (nCRT), and theoretically, these patients may be cured by CRT and omit surgery. This prospectively randomized pilot study compared definitive chemoradiotherapy (dCRT) with nCRT in patients with locally advanced ESCC who achieved clinical complete responses (cCRs) to nCRT.

Materials And Methods: Single center, randomized, open phase 2 study of 256 patients with locally advanced ESCC enrolled between April 2016 and November 2018. Immediately when nCRT finished, patients enrolled underwent response evaluations within 1 week. Patients with cCR were randomly allocated to undergo surgery (arm A) or complete CRT up to the definitive radiation dose (arm B). The primary end point was 3-year disease-free survival (DFS).

Results: Finally, 71 patients were randomly assigned to the nCRT (n = 36) and dCRT (n = 35) arms. The median observation time was 35.7 months. The 3-year DFS rate was 56.43 % in arm A versus 54.73 % in arm B (hazard ratio [HR] = 0.862, 95 % confidence interval [CI] = 0.452 to 1.645, P = 0.652). The 3-year overall survival (OS) rates in arms A and B were 69.5 % and 62.3 % (HR = 0.824, 95 % CI = 403-1.688, P = 0.597), respectively.

Conclusions: According to our treatment response evaluation criteria, survival of the patients with cCR after nCRT was not significant different between nCRT group and dCRT group. An optimized response evaluation strategy soon after nCRT may guide next therapy decisions for patients with locally advanced ESCC.
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http://dx.doi.org/10.1016/j.radonc.2022.06.015DOI Listing
June 2022

Optimizing the Construction and Update Strategies for the Genomic Selection of Pig Reference and Candidate Populations in China.

Front Genet 2022 8;13:938947. Epub 2022 Jun 8.

Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Optimizing the construction and update strategies for reference and candidate populations is the basis of the application of genomic selection (GS). In this study, we first simulated1200-purebred-pigs population that have been popular in China for 20 generations to study the effects of different population sizes and the relationship between individuals of the reference and candidate populations. The results showed that the accuracy was positively correlated with the size of the reference population within the same generation ( = 0.9366, < 0.05), while was negatively correlated with the number of generation intervals between the reference and candidate populations ( = -0.9267, < 0.01). When the reference population accumulated more than seven generations, the accuracy began to decline. We then simulated the population structure of 1200 purebred pigs for five generations and studied the effects of different heritabilities (0.1, 0.3, and 0.5), genotyping proportions (20, 30, and 50%), and sex ratios on the accuracy of the genomic estimate breeding value (GEBV) and genetic progress. The results showed that if the proportion of genotyping individuals accounts for 20% of the candidate population, the traits with different heritabilities can be genotyped according to the sex ratio of 1:1male to female. If the proportion is 30% and the traits are of low heritability (0.1), the sex ratio of 1:1 male to female is the best. If the traits are of medium or high heritability, the male-to-female ratio is 1:1, 1:2, or 2:1, which may achieve higher genetic progress. If the genotyping proportion is up to 50%, for low heritability traits (0.1), the proportion of sows from all genotyping individuals should not be less than 25%, and for the medium and high heritability traits, the optimal choice for the male-to-female ratio is 1:1, which may obtain the greatest genetic progress. This study provides a reference for determining a construction and update plan for the reference population of breeding pigs.
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http://dx.doi.org/10.3389/fgene.2022.938947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213789PMC
June 2022

Extracellular vesicles derived from bone marrow mesenchymal stem cells alleviate neurological deficit and endothelial cell dysfunction after subarachnoid hemorrhage via the KLF3-AS1/miR-83-5p/TCF7L2 axis.

Exp Neurol 2022 Oct 20;356:114151. Epub 2022 Jun 20.

Department of Neurosurgery Intensive Care Unit, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, PR China. Electronic address:

Background: New data are accumulating on the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in cerebrovascular diseases. We explored the potential role of KLF3-AS1-containing bone marrow MSC-EVs (BMSC-EVs) in a rat model of subarachnoid hemorrhage (SAH).

Methods: A rat model of SAH was established by endovascular perforation method, into which KLF3-AS1-containing EVs from BMSCs or miR-183-5p mimic were injected. Further, brain microvascular endothelial cells (BMECs) were induced by oxyhemoglobin (OxyHb) to simulate in vitro setting, which were co-cultured with KLF3-AS1-containing EVs from BMSCs. Effects of KLF3-AS1 on neurological deficits in vivo and endothelial cell dysfunction in vitro were investigated. We also performed bioinformatics analysis to predict downstream factors miR-183-5p and TCF7L2, which were verified by RIP, RNA pull-down and luciferase activity assays.

Results: BMSC-EVs was demonstrated to alleviate neurological deficits in SAH rats and endothelial cell dysfunction in OxyHb-induced BMECs. In addition, BMSC-EVs were shown to deliver KLF3-AS1 to BMECs, where KLF3-AS1 bound to miR-183-5p and miR-183-5p targeted TCF7L2. In vivo results confirmed that BMSC-EVs regulated the KLF3-AS1/miR-183-5p/TCF7L2 signaling axis to attenuate neurological deficit and endothelial dysfunction after SAH.

Conclusion: Overall, KLF3-AS1 delivered by BMSC-EVs upregulate TCF7L2 expression by binding to miR-138-5p, thus attenuating neurological deficits and endothelial dysfunction after SAH.
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http://dx.doi.org/10.1016/j.expneurol.2022.114151DOI Listing
October 2022

Emerging Biomaterials Imaging Antitumor Immune Response.

Adv Mater 2022 Jun 21:e2204034. Epub 2022 Jun 21.

Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing, 400715, P. R. China.

Immunotherapy is one of the most promising clinical modalities for the treatment of malignant tumors and has shown excellent therapeutic outcomes in clinical settings. However, it continues to face several challenges, including long treatment cycles, high costs, immune-related adverse events, and low response rates. Thus, it is critical to predict the response rate to immunotherapy by using imaging technology in the preoperative and intraoperative. Here, we comprehensively summarize the latest advances in nanosystem-based biomaterials used for predicting responses to immunotherapy via the imaging of immune cells and signaling molecules in the immune microenvironment. Several imaging methods, such as fluorescence imaging, magnetic resonance imaging, positron emission tomography imaging, ultrasound imaging, and photoacoustic imaging, used in immune predictive imaging, are discussed to show the potential of nanosystems for distinguishing immunotherapy responders from non-responders. Nanosystem-based biomaterials aided by various imaging technologies are expected to enable the effective prediction and diagnosis in cases of tumors, inflammation, and other public diseases. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204034DOI Listing
June 2022

Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline.

J Clin Oncol 2022 Jun 21:JCO2200868. Epub 2022 Jun 21.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.

Purpose: To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC).

Methods: An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations.

Results: The panel considered peer-reviewed reports published in English.

Recommendations: The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
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http://dx.doi.org/10.1200/JCO.22.00868DOI Listing
June 2022

A comprehensive evaluation of PM-bound PAHs and their derivative in winter from six megacities in China: Insight the source-dependent health risk and secondary reactions.

Environ Int 2022 07 11;165:107344. Epub 2022 Jun 11.

Key Lab of Aerosol Chemistry & Physics, SKLLQG, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an, China.

Atmospheric PAHs (polycyclic aromatic hydrocarbons) and their derivatives are a global concern that influences environments and threatens human health. Concentrations of 52 PAHs and the main derivatives in six Chinese megacities were measured in the winter of 2019. The concentrations of ∑PAHs (sum of 52 PAHs) ranged from 19.42 ± 7.68 to 65.40 ± 29.84 ng m, with significantly higher levels in northern cities (Harbin [HB], Beijing [BJ], and Xi'an [XA]) than southern ones (Wuhan [WH], Chengdu [CD] and Guangzhou [GZ]). Source apportionment of ∑PAHs was conducted by the PMF model and results showed coal combustion and traffic emissions were the two dominant sources, which dominated ∑PAHs in northern and southern cities, respectively. Biomass burning was also characterized as a crucial source of ∑PAHs and showed extremely high contributions in XA (42.5%). Assisted by the individual PAH source apportionment results, the source-depend TEQ (total BaP equivalent) and incremental lifetime cancer risk (ILCR) were firstly reported in these cities. The results highlighted the contributions of coal combustion and biomass burning to both TEQ and ILCR, which were underestimated by ∑PAHs source apportionment. Secondary organic aerosol-derived PAHs were demonstrated to increase the TEQ compared with the fresh PAHs and three parameters, namely temperature, relative humidity, and O concentrations were characterized by multiple linear regression as the principal factors influencing secondary reactions of PAHs in winter. This study provides accurate human health-orientated results and potential control measures to mitigate the toxicity of secondary formed PAHs, and significantly decrease the uncertainty level of traditional methods. The results also revealed great progress in air pollution control by the Chinese government in the past 20 years, but still a long way to go to formulate strict emission control strategies from both environmental and human health-protective perspectives.
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http://dx.doi.org/10.1016/j.envint.2022.107344DOI Listing
July 2022

Time-resolved proximity labeling of protein networks associated with ligand-activated EGFR.

Cell Rep 2022 Jun;39(11):110950

Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Ligand binding to the EGF receptor (EGFR) triggers multiple signal-transduction processes and promotes endocytosis of the receptor. The mechanisms of EGFR endocytosis and its cross-talk with signaling are poorly understood. Here, we combine peroxidase-catalyzed proximity labeling, isobaric peptide tagging, and quantitative mass spectrometry to define the dynamics of the proximity proteome of ligand-activated EGFR. Using this approach, we identify a network of signaling proteins, which remain associated with the receptor during its internalization and trafficking through the endosomal system. We show that Trk-fused gene (TFG), a protein known to function at the endoplasmic reticulum exit sites, is enriched in the proximity proteome of EGFR in early/sorting endosomes and localized in these endosomes and demonstrate that TFG regulates endosomal sorting of EGFR. This study provides a comprehensive resource of time-dependent nanoscale environment of EGFR, thus opening avenues to discovering new regulatory mechanisms of signaling and intracellular trafficking of receptor tyrosine kinases.
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http://dx.doi.org/10.1016/j.celrep.2022.110950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248364PMC
June 2022

Structural Model Construction and Optimal Characterization of High-Volatile Bituminous Coal Molecules.

ACS Omega 2022 Jun 23;7(22):18350-18360. Epub 2022 May 23.

CCTEG Shenyang Research Institute, Fushun 123000, China.

The structural characteristics of coal at the molecular level are important for its efficient use. Bituminous coal from the Baozigou Coal Mine is investigated, using elemental analysis, C nuclear magnetic resonance, X-ray photoelectron spectroscopy, and Fourier transform infrared. The molecular structure was determined. The aromatic compounds of bituminous coal molecules are primarily two- and three-ring structures, and the aliphatic structures are primarily in the form of methyl, ethyl side chains, and naphthenic hydrocarbons. The ratio of aromatic bridge carbon to peripheral carbon in the molecular structure is 0.279. Oxygen atoms in the form of carbonyl, phenolic hydroxyl and C-O, and nitrogen atoms in pyrroles. Thus, the average structure model of bituminous coal macromolecules was constructed; the molecular formula was CHONS, and the molecular weight was 2378. The aromatic structural units in the macromolecular structure of coal include four naphthalenes, three anthracenes, two tetracenes, and heteroatoms in the form of three carbonyl groups, one phenolic hydroxyl group, one pyrrole, and one pyridine. The structure optimization and annealing kinetic simulation of a single macromolecular structure model were performed. Chemical bonds such as bridge bonds and aliphatic bonds were found to be twisted, and π-π interactions between the aromatic sheets in the molecule produced adjacent aromatic sheets. This arrangement tends to be approximately parallel, and the total energy decreases from 6713.401 to 2667.595 kJ/mol, among which the bond stretching energy and van der Waals energy dominate. We used 20 bituminous coal macromolecular models to construct aggregated structural models. After optimization by molecular dynamics simulation, the macromolecules were constrained by the surrounding molecules, and the sheet-like aromatic carbon structures that were originally approximately parallel were distorted. The macromolecular structure model of bituminous coal constructed in this study provides a theoretical model basis for the optimal surfactant.
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http://dx.doi.org/10.1021/acsomega.2c00505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178619PMC
June 2022

Copy Number Variations Contribute to Intramuscular Fat Content Differences by Affecting the Expression of Alternative Splices in Pigs.

Animals (Basel) 2022 May 27;12(11). Epub 2022 May 27.

Key Laboratory of Farm Animal Genetic Resources and Germplasm Innovation of Ministry of Agriculture of China, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Intramuscular fat (IMF) is a key meat quality trait. Research on the genetic mechanisms of IMF decomposition is valuable for both pork quality improvement and the treatment of obesity and type 2 diabetes. Copy number variations (CNVs) are a type of variant that may influence meat quality. In this study, a total of 1185 CNV regions (CNVRs) including 393 duplicated CNVRs, 432 deleted CNVRs, and 361 CNVRs with both duplicated and deleted status were identified in a pig F2 resource population using next-generation sequencing data. A genome-wide association study (GWAS) was then performed between CNVs and IMF, and a total of 19 CNVRs were found to be significantly associated with IMF. QTL colocation analysis indicated that 3 of the 19 CNVRs overlapped with known QTLs. RNA-seq and qPCR validation results indicated that CNV150, which is located on the 3'UTR end of the proline, as well as glutamate and the leucine rich protein 1 () gene may affect the expression of alternative splices. Sequence alignment and Alphafold2 structure prediction results indicated that the two alternative splices of PELP1 have a 23 AA sequence variation and a helix-fold structure variation. This region is located in the region of interaction between PELP1 and other proteins which have been reported to be significantly associated with fat deposition or insulin resistance. We infer that the CNVR may influence IMF content by regulating the alternative splicing of the gene and ultimately affects the structure of the PELP1 protein. In conclusion, we found some CNVRs, especially CNV150, located in that affect IMF. These findings suggest a novel mechanistic approach for meat quality improvement in animals and the potential treatment of insulin resistance in human beings.
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http://dx.doi.org/10.3390/ani12111382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179479PMC
May 2022

Bimodal liquid biopsy for cancer immunotherapy based on peptide engineering and nanoscale analysis.

Biosens Bioelectron 2022 Oct 1;213:114445. Epub 2022 Jun 1.

Pharmaceutical Sciences Division and Wisconsin Center for NanoBioSystems (WisCNano), School of Pharmacy, University of Wisconsin - Madison, 777 Highland Ave, Madison, WI, 53705, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, 600 Highland Ave, WI, 53792, USA; Department of Biomedical Engineering, The University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53705, USA; Yonsei Frontier Lab, Department of Pharmacy, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. Electronic address:

Despite its high potential, PD-L1 expressed by tumors has not been successfully utilized as a biomarker for estimating treatment responses to immunotherapy. Circulating tumor cells (CTCs) and tumor-derived exosomes that express PD-L1 can potentially be used as biomarkers; however, currently available assays lack clinically significant sensitivity and specificity. Here, a novel peptide-based capture surface is developed to effectively isolate PD-L1-expressing CTCs and exosomes from human blood. For the effective targeting of PD-L1, this study integrates peptide engineering strategies to enhance the binding strength and specificity of a β-hairpin peptide derived from PD-1 (pPD-1). Specifically, this study examines the effect of poly(ethylene glycol) spacers, the secondary peptide structure, and modification of peptide sequences (e.g., removal of biologically redundant amino acid residues) on capture efficiency. The optimized pPD-1 configuration captures PD-L1-expressing tumor cells and tumor-derived exosomes with 1.5-fold (p = 0.016) and 1.2-fold (p = 0.037) higher efficiencies, respectively, than their whole antibody counterpart (aPD-L1). This enhanced efficiency is translated into more clinically significant detection of CTCs (1.9-fold increase; p = 0.035) and exosomes (1.5-fold increase; p = 0.047) from patients' baseline samples, demonstrating stronger correlation with patients' treatment responses. Additionally, we confirmed that the clinical accuracy of our system can be further improved by co-analyzing the two biomarkers (bimodal CTC/exosome analysis). These data demonstrate that pPD-1-based capture is a promising approach for capturing PD-L1-expressing CTCs and exosomes, which can be used as a reliable biomarker for cancer immunotherapy.
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http://dx.doi.org/10.1016/j.bios.2022.114445DOI Listing
October 2022

Three-Dimensional Echocardiography and Coagulation Function Detection in the Prognosis Evaluation of Patients with Acute Myocardial Infarction.

Comput Math Methods Med 2022 28;2022:5197871. Epub 2022 May 28.

Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing 100730, China.

This research was aimed at discussing the application value of coagulation function detection and three-dimensional echocardiography in the prognosis evaluation of acute myocardial infarction (AMI) patients. 72 patients with AMI were divided into the recovered group (good recovery) and unrecovered group (poor recovery) according to the results of postoperative ultrasonography. The left ventricular parameters of the patients were detected by three-dimensional ultrasound, and the coagulation function was also detected. The results showed that 3 months after surgery, the regional end-systolic volume (rESV) and regional end-diastolic volume (rEDV) of the left ventricle in the patients were smaller than the measured values 1 week after surgery. The left ventricular regional ejection fraction (rEF) was greater than the value measured 1 week after surgery, and all the differences were statistically significant ( < 0.05). For the end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction (EF) (%), the two-dimensional ultrasound results were significantly lower than the three-dimensional ultrasound results, and there were significant differences ( < 0.05). Tmsvle6-Dif% of the recovered patients was 14.99 ± 9.88 and 14.37 ± 9.78 3 months and 6 months after surgery, respectively. These were smaller than 30.91 ± 18.63 and 33.51 ± 17.96 of the unrecovered patients; the differences were of statistical significance ( < 0.05). Tmsvl6-SD% of recovered patients was 3.69 ± 2.47 and 3.61 ± 1.83 3 months and 6 months after surgery, respectively, which were also smaller than 7.38 ± 4.06 and 7.96 ± 2.82 of unrecovered patients, showing statistically significant difference ( < 0.05). The postoperative Tmsvle6-Dif% and Tmsvl6-SD% of the recovered group were lower than those of the unrecovered patients, with the statistically significant differences ( < 0.05). The level of coagulation factors in the recovered group was also significantly lower than that in the unrecovered group with the difference statistically significant ( < 0.05). The results suggested that three-dimensional echocardiography played an important role in the evaluation of cardiac conditions in AMI patients. The level of coagulation factors varied with the AMI condition of patients, and there was an obvious relationship between them, which could provide a reference value for the prognosis evaluation of patients.
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http://dx.doi.org/10.1155/2022/5197871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167121PMC
June 2022

Bioengineered nanogels for cancer immunotherapy.

Chem Soc Rev 2022 Jun 20;51(12):5136-5174. Epub 2022 Jun 20.

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy & Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing 400715, China.

Recent years have witnessed increasingly rapid advances in nanocarrier-based biomedicine aimed at improving treatment paradigms for cancer. Nanogels serve as multipurpose and constructed vectors formed intramolecular cross-linking to generate drug delivery systems, which is attributed predominantly to their satisfactory biocompatibility, bio-responsiveness, high stability, and low toxicity. Recently, immunotherapy has experienced unprecedented growth and has become the preferred strategy for cancer treatment, and mainly involves the mobilisation of the immune system and an enhanced anti-tumour immunity of the tumour microenvironment. Despite the inspiring success, immunotherapeutic strategies are limited due to the low response rates and immune-related adverse events. Like other nanomedicines, nanogels are comparably limited by lower focal enrichment rates upon introduction into the organism injection. Because nanogels are three-dimensional cross-linked aqueous materials that exhibit similar properties to natural tissues and are structurally stable, they can comfortably cope with shear forces and serum proteins in the bloodstream, and the longer circulation life increases the chance of nanogel accumulation in the tumour, conferring deep tumour penetration. The large specific surface area can reduce or eliminate off-target effects by introducing stimuli-responsive functional groups, allowing multiple physical and chemical modifications for specific purposes to improve targeting to specific immune cell subpopulations or immune organs, increasing the bioavailability of the drug, and conferring a low immune-related adverse events on nanogel therapies. The slow release upon reaching the tumour site facilitates long-term awakening of the host's immune system, ultimately achieving enhanced therapeutic effects. As an effective candidate for cancer immunotherapy, nanogel-based immunotherapy has been widely used. In this review, we mainly summarize the recent advances of nanogel-based immunotherapy to deliver immunomodulatory small molecule drugs, antibodies, genes and cytokines, to target antigen presenting cells, form cancer vaccines, and enable chimeric antigen receptor (CAR)-T cell therapy. Future challenges as well as expected and feasible prospects for clinical treatment are also highlighted.
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http://dx.doi.org/10.1039/d2cs00247gDOI Listing
June 2022

First-Line Treatments for Metastatic Clear Cell Renal Cell Carcinoma: An Ever-Enlarging Landscape.

Oncologist 2022 03;27(2):125-134

Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.

Treatment paradigm for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the recent decades. From cytokines, interleukin-2 and interferon-α to tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, during the last decade, combinations of immune checkpoint inhibitors have taken over first-line treatment of mccRCC. These combinations are approved based on results from large phase III clinical trials, all of which used sunitinib as the comparator. These trials include CheckMate214 (ipilimumab plus nivolumab), KEYNOTE 426 (pembrolizumab plus axitinib), JAVELIN Renal 101 (avelumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), and the CLEAR study (lenvatinib and pembrolizumab). Results from these studies constitute milestones for newer therapeutic approaches in mccRCC. The broadening spectrum of treatment options for patients with mccRCC with multiple first-line options currently available also means that treating physicians will need to consider each option carefully, balance clinical factors, financial considerations, and weigh toxicity profiles of each drug before deciding the optimal treatment regimen for each individual patient. We describe each frontline treatment option in detail through this review to aid the decision-making process.
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http://dx.doi.org/10.1093/oncolo/oyab056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895741PMC
March 2022

Superior mechanical flexibility, lattice thermal conductivity and electron mobility of the hexagonal honeycomb carbon nitride monolayer.

Phys Chem Chem Phys 2022 Jun 8;24(22):13951-13964. Epub 2022 Jun 8.

School of Physics and Electronic Engineering, Sichuan Normal University, Chengdu 610066, China.

Nitrogen is the nearest neighbor element of carbon and, thus, the hexagonal honeycomb carbon nitride monolayer (CN), which consists of a covalent network of carbon and nitrogen atoms, usually has attractive physical and chemical properties similar to those in graphene. Here, we systematically investigate the geometric structure, mechanical properties, thermal transport properties, and plasmon excitation of a new phase, labeled CN, and make a detailed comparison with other possible CN allotropes. All CN have a super-high layer modulus and Young's modulus. But compared with the others, CN exhibits excellent mechanical flexibility, and can withstand a relatively high critical strain up to 20% (18%) along the () direction. Additionally, CN also has excellent thermal and electronic transport properties, with a super-high lattice thermal conductivity of ∼110.9 W m K and electron mobility of ∼1617.52 cm V s at 300 K. By performing time-dependent density functional theory (TDDFT), we obtain the optical absorptions of CN and CN, and meanwhile analyze their Fourier transforms of induced charge densities at some resonant frequencies. The main optical absorption peaks of the CN nanostructure are located in the ultraviolet region, and its plasmon peaks are far higher than those in CN. Its excellent mechanical and optical properties, the larger electronic band gap, and the higher electron mobility suggest that CN has great potential for application in nanoelectronics and optoelectronics.
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http://dx.doi.org/10.1039/d2cp01104bDOI Listing
June 2022

The serum soluble Klotho alleviates cardiac aging and regulates M2a/M2c macrophage polarization via inhibiting TLR4/Myd88/NF-κB pathway.

Tissue Cell 2022 Jun 4;76:101812. Epub 2022 May 4.

Department of Pathophysiology, College of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang 830000, China; Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Urumqi 830000, China. Electronic address:

Aging is a continuous and irreversible process that leads to a progressive deterioration in cardiac geometry and function. Klotho is an anti-aging protein with cardioprotective effect. However, the relationship between Klotho and cardiac aging and its possible mechanism are not completely clear. We applied D-galactosamine (D-Gal) to replicate cardiac senescence by increasing oxidative stress in the heart. M2 anti-inflammatory markers in the aging hearts were observed significantly lower than those in adult mice. Therefore, in this study, we demonstrated that serum soluble Klotho (sKL) could exert its cardioprotective and anti-inflammatory effects by regulating the phenotype of macrophages by inhibiting TLR4/MyD88/NF-κB. In terms of mechanism, supplementation of serum soluble Klotho can prevent excessive oxidative stress, inflammation, apoptosis and cardiac dysfunction in the aging heart. In RAW264.7 cells, sKL induced macrophages to differentiate into M2a/M2c macrophages, and the culture supernatant of M2a/M2c macrophages significantly reversed the senescence of cardiomyocytes and improved myocardial viability compared with the control group. Therefore, supplementation of sKL can improve aging cardiac function, reduce cardiac oxidative stress, inflammation and apoptosis by promoting M2a/M2c polarized macrophages via inhibiting the TLR4/Myd88/NF-κB pathway.
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http://dx.doi.org/10.1016/j.tice.2022.101812DOI Listing
June 2022

Patient- And Provider-Level Predictors of Survival Among Patients With Metastatic Renal Cell Carcinoma Initiating Oral Anticancer Agents.

Clin Genitourin Cancer 2022 Apr 25. Epub 2022 Apr 25.

Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, NC; Lineberger Comprehensive Cancer Center (LCCC), UNC-CH, Chapel Hill, NC, USA; Duke Cancer Institute (DCI), DUSM, Durham, NC, USA.

Purpose: In an era of rapid expansion of FDA approvals for oral anticancer agents (OAAs), it is important to understand the factors associated with survival among real-world populations, which include groups not well-represented in pivotal clinical trials of OAAs, such as the elderly, racial minorities, and medically complex patients. Our objective was to evaluate patient- and provider-level characteristics' associations with mortality among a multi-payer cohort of metastatic renal cell carcinoma (mRCC) patients who initiated OAAs.

Methods: This retrospective cohort study was conducted using data from the North Carolina state cancer registry linked to multi-payer claims data for the years 2004 to 2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. Included patients were individuals with mRCC who initiated an OAA and survived ≥90 days after beginning treatment. We estimated hazard ratios (HR) and corresponding 95% confidence limits (CL) using Cox hazard models for associations between patient demographics, patient clinical characteristics, provider-level factors, and 2-year all-cause mortality.

Results: The cohort included 207 patients with mRCC who received OAAs. In multivariable models, clinical variables such as frailty (HR: 1.36, 95% CL: 1.11-1.67) and de novo metastatic diagnosis (HR: 2.63, 95%CL: 1.67-4.16) were associated with higher all-cause mortality. Additionally, patients solely on Medicare had higher adjusted all-cause mortality compared with patients with any private insurance (HR: 2.35, 95% CL: 1.32-4.18). No provider-level covariates investigated were associated with all-cause mortality.

Conclusions: Within a real-world population of mRCC patients taking OAAs, survival differed based on patient characteristics. In an era of rapid expansion of FDA approvals for OAAs, these real-world data underscore the continued importance of access to high-quality care, particularly for medically complex patients with limited resources.
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http://dx.doi.org/10.1016/j.clgc.2022.04.010DOI Listing
April 2022
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