Publications by authors named "Xiang Chen"

1,890 Publications

  • Page 1 of 1

Clinical Observation and Value Analysis of Endovascular Interventional Therapy for Intracranial Venous Sinus Thrombosis.

Biomed Res Int 2022 14;2022:4931210. Epub 2022 Jun 14.

Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.

The main aim of this study was to investigate the therapeutic effect of endovascular interventional therapy on cerebral venous sinus thrombosis (CVST). 137 patients with CVST were included, 92 patients were treated with interventional therapy, and 45 patients were treated with conventional anticoagulant therapy. Through endovascular therapy (EVT) combined with therapy, the patients were treated with EVT in combination with conventional anticoagulant therapy, and the prognosis of the two groups of patients was evaluated. The results showed that 26 patients were complicated with female-specific infections in the combined EVT group, and 7 patients had female-specific infections in the simple anticoagulant therapy (LMWH) group. In terms of central nervous system infections, the EVT group was significantly lower than the LMWH group, < 0.001, and the difference was statistically significant. There were 2 cases of EVT involving the inferior sagittal sinus and 12 cases of LMWH involving the inferior sagittal sinus, < 0.001, and the difference had statistical significance. Through the RANKIN scale (mRS) score, it was classified as complete recovery and good prognosis (dependent variable). The patients receiving EVT with good prognosis (96.7%) were more than those receiving simple anticoagulant therapy (84.4%), and 78.3% were completely recovered after EVT, and 77.5% were completely recovered after anticoagulant therapy. Therefore, it can be concluded that gender, malignant tumors, thrombosis, and sinuses are all risk factors affecting the prognosis of patients; both endovascular interventional therapy and anticoagulant therapy can significantly improve the prognosis of patients.
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http://dx.doi.org/10.1155/2022/4931210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213190PMC
June 2022

Oil spills enhanced dispersion and transport of microplastics in sea water and sand at coastal beachheads.

J Hazard Mater 2022 Aug 7;436:129312. Epub 2022 Jun 7.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National Field Observation and Research Station of Erhai Lake Ecosystem, Yunnan 671000, China; Shanghai Engineering Research Center of Solid Waste Treatment and Resource Recovery, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

The coastal zone is being under the threat by accumulation of microplastics (MPs), with much of MPs ending up on the beachhead. Oil spills, which frequently happen in coastal zones due to oil pipe leakage or oil drilling, may affect the behavior of MPs in the beachheads. Herein, sea water and sea sand were collected from three different coastal beachheads including Bohai Sea (BS), East Sea (ES), and South Sea (SS), China, to investigate how the oil spills affect the dispersion and transport of MPs in sea water and sand. The oil spills greatly enhanced the dispersion of MPs in all three sea waters by forming MPs-oil-dispersant agglomerates, which increased the electrostatic repulsion and steric hindrance between MPs particles. Accordingly, the aggregation rates of MPs were reduced from 1.7-8.86 nm min to 0.39-1.29 nm min. The lowest salinity and highest dissolved organic carbon content in SS sea water favored the highest dispersion of MPs, compared to BS and ES sea water. The improved dispersion of MPs with oil spills enhanced their transport in sea sand with an increase of effluent rates from 0-18.8 % to 5.78-42.2 % for BS and from 30.5-45.2 % to 35.0-60.0 % for SS one. However, the transport of MPs in ES sea sand was lower than 3.62 %, even with oil spills, which was attributed to the strong adsorption of MPs by the rich Fe/Al oxides in ES sea sand through electric attraction. Modeling also showed that oil spills increased the migration rate of 10 mg g MPs accumulated in the surface 0-1 cm sea sand from 6.50-13.8 cm year to 8.17-16.7 cm year after 1500 mm rainfall for 3 years, and the strongest transport of MPs was observed in SS sea sand, with the highest cumulative flux and the longest maximum migration depth as 0.089-0.120 mg/cm and 50 cm, respectively. These results indicated that the dispersion and transport of MPs can be enhanced by oil spills, but regulated by sea water salinity for MPs dispersion and sea sand Fe/Al oxides for MPs transport, which advanced our understanding of the transport and transformation of MPs in coastal zones.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129312DOI Listing
August 2022

Chiral RuII-PtII Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells.

Angew Chem Int Ed Engl 2022 Jun 23. Epub 2022 Jun 23.

Sun Yat-Sen University, Chemistry, Xingang Xilu 135#, 510275, Guangzhou, CHINA.

The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral Ru(II)-Pt(II) dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a Ru(II)-Pt(II) dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.
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http://dx.doi.org/10.1002/anie.202204866DOI Listing
June 2022

Topical VX-509 Attenuates Psoriatic Inflammation Through the STAT3/FABP5 Pathway in Keratinocytes.

Pharmacol Res 2022 Jun 18:106318. Epub 2022 Jun 18.

The Department of Dermatology, Xiangya Hospital, Central South University; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University. Electronic address:

Background: Psoriasis is a chronic inflammatory disease, with lesions mainly manifesting as scaly erythematous plaques. The mild or moderate of psoriasis is the main type of patients in hospital, and topical application remains the preferred treatment option for psoriasis therapy, therefore, the development of novel topical agents has an essential role in psoriasis therapy.

Objective: To identify potential drugs for psoriasis topical treatment.

Methods: We performed drug screening by Imiquimod (IMQ)-induced psoriatic like inflammation in mouse model, followed mouse epidermis by RNA-seq to find the key molecules affecting the drug. The qRT-PCR, WB were performed to test mRNA and protein expression, and Chip assay had been conducted to examine Stat3 bound to promoter of FABP5.

Results: In this study, we identified VX-509, which topical application significantly attenuated IMQ-induced psoriatic like inflammation in mouse model. And then, we verified Epidermal Fatty acid binding protein (E-FABP/FABP5) was significantly decreased in VX-509 treated mouse epidermis by RNA-seq. FABP5 is a key molecule in lipid metabolism, administration of FABP5 inhibitor or knock down of FABP5 expression remarkably abrogated psoriatic inflammation as well as lipid metabolism. Mechanistically, our finding showed that VX-509 blocked IL-22 induced signaling pathway, particular in activation of Stat3. Furthermore, we identified Stat3 is a transcriptional factor associated with FABP5 promoters and VX-509 treatment remarkably attenuated IL-22-induced FABP5 expression through Stat3 in KCs.

Conclusions: This study demonstrated administration of VX-509 is a potential promising topical drug for treatment of psoriasis, FABP5 is a critical targeted molecule in psoriasis therapy.
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http://dx.doi.org/10.1016/j.phrs.2022.106318DOI Listing
June 2022

[Development and validation of a predictive model for the risk of 30-day death in emergency department patients].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Apr;34(4):421-425

Department of Nursing, the First People's Hospital of Changde, Changde 415000, Hunan, China. Corresponding author: Tong Li, Email:

Objective: To explore the risk factors for 30-day death in emergency department patients, and then construct a prediction model and validate it using nomogram.

Methods: A retrospective cohort study was conducted. The clinical data of 1 091 patients admitted to the emergency department of the First People's Hospital of Changde from January 1 to June 30, 2021 was collected, including 741 patients from January 1 to March 31 in the development group and 350 patients from April 1 to June 30 in the validation group. General information, first vital signs admitted to the emergency department, and laboratory results were collected, the modified early warning score (MEWS) was calculated, and 30-day outcomes were recorded. Univariate and multivariate Logistic regression analysis was used to screen out the risk factors of 30-day death. According to the results of multivariate analysis, the nomogram was used to construct a 30-day death prediction model. The receiver operator characteristic curve (ROC curve) was used to evaluate the consistency of the prediction model, the calibration of the prediction model was evaluated by the Hosmer-Lemeshow goodness of fit test.

Results: A total of 1 091 patients were enrolled. There were 741 patients in the development group, including 356 males and 385 females, aged (51.42±17.33) years old, and the 30-day mortality was 28.88%. There were 350 patients in the validation group, including 188 males and 162 females, aged (52.88±16.11) years old, and the 30-day mortality was 24.00%. The results of the univariate analysis showed that age, primary diagnosis on admission, consciousness, respiratory rate (RR), systolic blood pressure (SBP), heart rate (HR), pulse oxygen saturation (SpO), MEWS score, erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and body mass index (BMI) might be the risk factors for 30-day death in patients in the emergency department. The results of the multivariate analysis showed that the MEWS score [odds ratio (OR) = 14.22, 95% confidence interval (95%CI) was 1.46-138.12], ESR (OR = 46.71, 95%CI was 20.48-106.53), PCT (OR = 4.97, 95%CI was 2.46-10.02), BMI (24.0-27.9 kg/m: OR = 37.82, 95%CI was 14.69-97.36; ≥ 28.0 kg/m: OR = 62.11, 95%CI was 25.77-149.72) were independent risk factors for 30-day death in the emergency department (all P < 0.05). Using the four variables with the results of multivariate analysis to construct a nomogram prediction model, the area under the ROC curve (AUC) was 0.974 (95%CI was 0.753-0.983) for the development group, and the AUC was 0.963 (95%CI was 0.740-0.975) for the validation group. The Hosmer-Lemeshow test showed no statistically significant difference between the predicted outcome of the nomogram prediction model and the actual occurrence (χ = 1.216, P = 1.270).

Conclusion: The prediction model developed by the MEWS score combined with BMI, ESR and PCT can scientifically and effectively predict the 30-day outcome of emergency department patients.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210830-01291DOI Listing
April 2022

Pervasive beyond Room-Temperature Ferromagnetism in a Doped van der Waals Magnet.

Phys Rev Lett 2022 May;128(21):217203

Materials Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA.

The existence of long-range magnetic order in low-dimensional magnetic systems, such as the quasi-two-dimensional van der Waals (vdW) magnets, has attracted intensive studies of new physical phenomena. The vdW Fe_{N}GeTe_{2} (N=3, 4, 5; FGT) family is exceptional, owing to its vast tunability of magnetic properties. In particular, a ferromagnetic ordering temperature (T_{C}) above room temperature at N=5 (F5GT) is observed. Here, our study shows that, by nickel (Ni) substitution of iron in F5GT, a record high T_{C}=478(6)  K is achieved. Importantly, pervasive, beyond room-temperature ferromagnetism exists in almost the entire doping range of the phase diagram of Ni-F5GT. We argue that this striking observation in Ni-F5GT can be possibly due to several contributing factors, including increased 3D magnetic couplings due to the structural alterations.
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http://dx.doi.org/10.1103/PhysRevLett.128.217203DOI Listing
May 2022

Frequency-Domain Detection for Frequency-Division Multiplexing QEPAS.

Sensors (Basel) 2022 May 26;22(11). Epub 2022 May 26.

Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

To achieve multi-gas measurements of quartz-enhanced photoacoustic spectroscopy (QEPAS) sensors under a frequency-division multiplexing mode with a narrow modulation frequency interval, we report a frequency-domain detection method. A CH absorption line at 1653.72 nm and a CO absorption line at 2004.02 nm were investigated in this experiment. A modulation frequency interval of as narrow as 0.6 Hz for CH and CO detection was achieved. Frequency-domain 2 signals were obtained with a resolution of 0.125 Hz using a real-time frequency analyzer. With the multiple linear regressions of the frequency-domain 2 signals of various gas mixtures, small deviations within 2.5% and good linear relationships for gas detection were observed under the frequency-division multiplexing mode. Detection limits of 0.6 ppm for CH and 2.9 ppm for CO were simultaneously obtained. With the 0.6-Hz interval, the amplitudes of QEPAS signals will increase substantially since the modulation frequencies are closer to the resonant frequency of a QTF. Furthermore, the frequency-domain detection method with a narrow interval can realize precise gas measurements of more species with more lasers operating under the frequency-division multiplexing mode. Additionally, this method, with a narrow interval of modulation frequencies, can also realize frequency-division multiplexing detection for QEPAS sensors under low pressure despite the ultra-narrow bandwidth of the QTF.
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http://dx.doi.org/10.3390/s22114030DOI Listing
May 2022

Working Zinc-Air Batteries at 80oC.

Angew Chem Int Ed Engl 2022 Jun 9. Epub 2022 Jun 9.

Tsinghua University, Department of Chemical Engineering, No.1, Tsinghua Road, 100084, Beijing, CHINA.

Aqueous zinc-air batteries possess inherent safety and are especially commendable facing high-temperature working conditions. However, their working feasibility at high temperatures has seldom been investigated. Herein, the working feasibility of high-temperature zinc-air batteries is systemically investigated. The effects of temperature on air cathode, zinc anode, and aqueous electrolyte are decoupled to identify the favorable and unfavorable factors. Specifically, parasitic hydrogen evolution reaction strengthens at high temperatures and leads to declined anode Faraday efficiency, which is identified as the main bottleneck. Moreover, zinc-air batteries demonstrate cycling feasibility at 80 o C. This work reveals the potential of zinc-air batteries to satisfy energy storage at high temperatures and guides further development of advanced batteries towards harsh working conditions.
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http://dx.doi.org/10.1002/anie.202208042DOI Listing
June 2022

Transdermal insulin delivery and microneedles-based minimally invasive delivery systems.

Curr Pharm Des 2022 Jun 8. Epub 2022 Jun 8.

State Key Laboratory of Chemial Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. China.

Diabetes has become a serious threat to human health, causing death and pain to numbers of patients. Transdermal insulin delivery is a substitute to traditional insulin injection avoiding pain from injection. Transdermal methods include the non-invasive methods and the invasive ones. As the non-invasive methods could hardly get through the stratum corneum, minimally invasive devices especially microneedles could enhance the transappendageal route in transcutaneous insulin delivery, and could act as connectors between tissue and outer environment or devices. Microneedle patches have been in quick development in recent years and with different types, materials and functions. In those patches, the smart microneedle patch could perform as a sensor and reactor responding to glucose to regulate the blood level. In the smart microneedles field, the phenylboronic acid system and the glucose oxidase system have been successfully applied on microneedle platform. Insulin transdermal delivery strategy, microneedles technology and smart microneedles' development would be discussed in this review.
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http://dx.doi.org/10.2174/1381612828666220608130056DOI Listing
June 2022

Reprogramming Mitochondrial Metabolism in Synovial Macrophages of Early Osteoarthritis by a Camouflaged Meta-Defensome.

Adv Mater 2022 Jun 7:e2202715. Epub 2022 Jun 7.

State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, P. R. China.

Osteoarthritis (OA) is a low-grade inflammatory and progressive joint disease, and its progression is closely associated with an imbalance in M1/M2 synovial macrophages. Repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype is emerging as a strategy to alleviate OA progression but is compromised by unsatisfactory efficiency. In this study, the reprogramming of mitochondrial dysfunction is pioneered with a camouflaged meta-Defensome, which can transform M1 synovial macrophages into the M2 phenotype with a high efficiency of 82.3%. The meta-Defensome recognizes activated macrophages via receptor-ligand interactions and accumulates in the mitochondria through electrostatic attractions. These meta-Defensomes are macrophage-membrane-coated polymeric nanoparticles decorated with dual ligands and co-loaded with S-methylisothiourea and MnO . Meta-Defensomes are demonstrated to successfully reprogram the mitochondrial metabolism of M1 macrophages by scavenging mitochondrial reactive oxygen species and inhibiting mitochondrial NO synthase, thereby increasing mitochondrial transcription factor A expression and restoring aerobic respiration. Furthermore, meta-Defensomes are intravenously injected into collagenase-induced osteoarthritis mice and effectively suppress synovial inflammation and progression of early OA, as evident from the Osteoarthritis Research Society International score. Therefore, reprogramming the mitochondrial metabolism can serve as a novel and practical approach to repolarize M1 synovial macrophages. The camouflaged meta-Defensomes are a promising therapeutic agent for impeding OA progression in tclinic.
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http://dx.doi.org/10.1002/adma.202202715DOI Listing
June 2022

Correction to: Genome‑wide identification and expression analysis of MYB gene family under nitrogen stress in Panax notoginseng.

Protoplasma 2022 Jun 7. Epub 2022 Jun 7.

Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China.

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http://dx.doi.org/10.1007/s00709-022-01782-xDOI Listing
June 2022

Apolipoprotein A1 inhibits adipogenesis progression of human adipose-derived mesenchymal stem cells.

Curr Mol Med 2022 Jun 7. Epub 2022 Jun 7.

Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, China.

Background: According to the reports, the most vital characteristic of obesity is aberrant accumulation of triglyceride (TG) in the adipocyte. On the other hand, circulating concentrations of apolipoprotein A1 (apoA1) have been demonstrated to be strongly correlated with the prevalence and the pathological development of obesity. Nevertheless, the underlying mechanisms whereby apoA1 modulates the pathogenesis of obesity is still not fully elucidated.

Methods: Adipose-derived mesenchymal stem cells (AMSCs, isolated from the hospitalized patients were intervened with 15 μg/ml recombined human apoA1 protein. The effects of apoA1 in modulating the intracellular levels of TG and the expression contents of adipogenic related cytokines were also analyzed. Furthermore, whether apoA1 modulated the adipogenesis progression was via sortilin was also explored in the current research.

Results: During the adipogenesis progression, apoA1 could significantly lower the quantity of intracellular lipid droplets (LDs). Meanwhile, apoA1 could decrease the intracellular levels of TG and down-regulate the expression contents of several vital adipogenic related cytokines, such as CCAAT enhancer binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid binding protein 4 (FABP4). Moreover, the inhibitory effect of apoA1 was further verified to be induced through up-regulating the SORT1 gene expression which subsequently increased sortilin protein. Consistent with these findings, silencing the SORT1 gene expression could induce the loss-of-function (LOF) of apoA1 in modulating the adipogenesis progression of AMSCs.

Conclusions: In conclusion, apoA1 could suppress the adipogenesis progression of human AMSCs through, at least partly, up-regulating the SORT1 gene expression which subsequently increasing the sortilin protein content. Thereby, the present research sheds light on a novel pathogenic mechanism by which apoA1 regulates adipogenesis progression and proposes that apoA1 embraces the function to treat obesity in clinical practice.
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http://dx.doi.org/10.2174/1566524022666220607085908DOI Listing
June 2022

Automatic 3D+t four-chamber CMR quantification of the UK biobank: integrating imaging and non-imaging data priors at scale.

Med Image Anal 2022 May 27;80:102498. Epub 2022 May 27.

Centre for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), School of Computing, University of Leeds, Leeds, UK; Biomedical Imaging Department, Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Electrical Engineering, KU Leuven, Leuven, Belgium; Alan Turing Institute, London, UK. Electronic address:

Accurate 3D modelling of cardiac chambers is essential for clinical assessment of cardiac volume and function, including structural, and motion analysis. Furthermore, to study the correlation between cardiac morphology and other patient information within a large population, it is necessary to automatically generate cardiac mesh models of each subject within the population. In this study, we introduce MCSI-Net (Multi-Cue Shape Inference Network), where we embed a statistical shape model inside a convolutional neural network and leverage both phenotypic and demographic information from the cohort to infer subject-specific reconstructions of all four cardiac chambers in 3D. In this way, we leverage the ability of the network to learn the appearance of cardiac chambers in cine cardiac magnetic resonance (CMR) images, and generate plausible 3D cardiac shapes, by constraining the prediction using a shape prior, in the form of the statistical modes of shape variation learned a priori from a subset of the population. This, in turn, enables the network to generalise to samples across the entire population. To the best of our knowledge, this is the first work that uses such an approach for patient-specific cardiac shape generation. MCSI-Net is capable of producing accurate 3D shapes using just a fraction (about 23% to 46%) of the available image data, which is of significant importance to the community as it supports the acceleration of CMR scan acquisitions. Cardiac MR images from the UK Biobank were used to train and validate the proposed method. We also present the results from analysing 40,000 subjects of the UK Biobank at 50 time-frames, totalling two million image volumes. Our model can generate more globally consistent heart shape than that of manual annotations in the presence of inter-slice motion and shows strong agreement with the reference ranges for cardiac structure and function across cardiac ventricles and atria.
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http://dx.doi.org/10.1016/j.media.2022.102498DOI Listing
May 2022

Numerical Modeling of Fracture Height Propagation in Multilayer Formations Considering the Plastic Zone and Induced Stress.

ACS Omega 2022 May 17;7(21):17868-17880. Epub 2022 May 17.

Petroleum Engineering Technology Institute of Southwest Petroleum Branch, SINOPEC, Deyang, Sichuan 618000, China.

Hydraulic fracturing and acid fracturing are very effective stimulation technologies and are widely used in unconventional reservoir development. Fracture height, as an essential parameter to describe the geometric size of a fracture, is not only the input parameter of two-dimensional fracturing models but also the output parameter of three-dimensional fracturing models. Accurate prediction of fracture height growth can effectively avoid some risks. For example, petroleum reservoirs produce a large amount of formation water because wrong fracture height prediction leads to the connection between the oil or gas reservoir and the water layer. Although some fracture height prediction models were developed, few models considered the effects of the plastic zone, induced stress, and heterogeneous multilayer formation and its interaction. Therefore, considering the influence of many factors, an improved fracture-equilibrium-height model was developed in this study. The successive over-relaxation iteration method and the displacement discontinuity method were used to solve the model. We investigated the effects of the geological and engineering factors on fracture height growth by using the model, and some important conclusions were obtained. The higher the fracture height, the larger the plastic zone size, and the more obvious its influence on fracture height propagation. High overlying or underlying in situ stress and fracture toughness and low fluid density played a positive role in limiting the growth of the fracture height. Induced stress caused by fracture 1 could not only inhibit the height growth of fracture 2 but also promote its growth. The model established in this paper could be coupled to a fracturing simulator to provide a more reliable fracture height prediction.
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http://dx.doi.org/10.1021/acsomega.2c01131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161263PMC
May 2022

EEAM 10B Strengthens Nutrient Metabolic Process in Black Soldier Fly Larvae () Changing Gut Microbiome and Metabolic Pathways.

Front Nutr 2022 19;9:880488. Epub 2022 May 19.

Department of Microbiology, School of Life Sciences, Henan Agricultural University, Key Laboratory of Agricultural Microbial Enzyme Engineering (Ministry of Agriculture), Zhengzhou, China.

Insects are a potential alternative protein source to solve the food shortage crisis. Previous studies have illustrated that probiotics can improve the substrate conversion efficiency of insects and increase insect protein content. However, the effects of probiotics on insect physiology and nutrient metabolism are still not well understood. Here, the black soldier fly larvae (BSFL), (Diptera: Stratiomyidae), was used as a study subject to deeply investigate the specific interaction among a novel probiotic, EEAM 10B (10B), intestinal microbiota, and the host. In this study, the effects of 10B on the survival and physiology of BSFL were first analyzed. It shows that 10B significantly elevated the substrate conversion rate, average dry weight, and protein content of BSFL by 5%, 0.13 g/pc, and 8%, respectively. Then, we assessed the effect of 10B on the microbial community composition in the gut and frass of BSFL using Illumina Miseq sequencing. It shows that 10B significantly altered the microbial composition of the gut, but not that of the frass. Pearson's correlation analysis further showed that the , , and were positively correlated with the survival rate, crude protein content, and substrate conversion rate of BSFL. To further investigate the effect of 10B on host metabolism, metabolic analyses on germ-free BSFL, monobacterial intestinal BSFL, and natural BSFL were also performed. The results proved that 10B (i) played a vital role in the survival of BSFL; and (ii) regulated the amino acid synthetic and metabolic process of BSFL, thus leading to the rise of the protein content of BSFL. In addition, vitamin backfill assays verified that the BSFL survival rate was significantly improved by supplying the germ-free BSFL with riboflavin, which further suggests that 10B determines the survival of BSFL delivering riboflavin. Overall, this study provides a reference for understanding the comprehensive contribution of a specific probiotic to its host.
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http://dx.doi.org/10.3389/fnut.2022.880488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161358PMC
May 2022

Platelet-Derived Amyloid-β Protein Precursor as a Biomarker of Alzheimer's Disease.

J Alzheimers Dis 2022 Jun 3. Epub 2022 Jun 3.

Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China.

Background: Platelet proteins may be associated with Alzheimer's disease (AD) pathology.

Objective: To investigate the relationship between platelet proteins and cerebrospinal fluid (CSF) biomarkers of AD and cognition in individuals with memory decline to identify effective screening methods for detecting the early stages of the disease.

Methods: We classified 68 participants with subjective memory decline according to the ATN framework determined by CSF amyloid-β (A), CSF p-tau (T), and t-tau (N). All participants underwent Mini-Mental State Examination (MMSE) and platelet-related protein content testing.

Results: Eighteen participants had normal AD biomarkers (NCs), 24 subjects had non-AD pathologic changes (non-AD), and 26 subjects fell within the Alzheimer's continuum (AD). The platelet amyloid-β protein precursor (AβPP) ratio in the AD group was significantly lower than in the non-AD and NCs groups, and positively correlated with MMSE scores and CSF amyloid-β42 level, which could affect MMSE scores through CSF amyloid-β42. Levels of platelet phosphorylated-tau 231 and ser396/404 phosphorylated tau were elevated in both AD and non-AD compared to NCs. Additionally, the receiver operating characteristic analysis demonstrated that the platelet AβPP ratio was a sensitive identifier for differentiating the AD from NCs (AUC = 0.846) and non-AD (AUC = 0.768). And ser396/404 phosphorylated tau could distinguish AD from NCs.

Conclusion: Our study was the first to find an association between platelet AβPP ratio and CSF biomarkers of AD, which contribute to the understanding of the peripheral changes in AD. These findings may help to discover potential feasible and effective screening tools for AD.
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http://dx.doi.org/10.3233/JAD-220122DOI Listing
June 2022

NUPR1 promotes the proliferation and migration of breast cancer cells by activating TFE3 transcription to induce autophagy.

Exp Cell Res 2022 Jun 2;418(1):113234. Epub 2022 Jun 2.

Surgery Department of Galactophore, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou, 412000, Hunan Province, PR China. Electronic address:

Recurrence and metastasis affect the survival rate of breast cancer patients. The fundamental reason lies in the lack of understanding of the mechanism of breast cancer metastasis. In this study, the proliferation, migration and invasion abilities of breast cancer cells were evaluated. The mechanism of NUPR1/TFE3 signaling pathway on autophagy-related proteins and migration-invasion-related proteins was examined in cell model in vitro. The effects of NUPR1 on malignancy formation and metastasis were investigated in vivo. We found that NUPR1 was upregulated in breast cancer cells and tissues. NUPR1 knockdown inhibited the proliferation, migration and invasion of ZR-75-30 cells and inhibited malignancy formation and metastasis in vivo. Mechanically, NUPR1 promoted autophagy by activating of TFE3 transcription, thereby regulating breast cancer metastasis. This paper indicates that NUPR1 activates autophagy through the TFE3 signaling pathway to promote breast cancer metastasis, and provides a biological basis for the intervention of blocking distant metastasis.
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http://dx.doi.org/10.1016/j.yexcr.2022.113234DOI Listing
June 2022

UVB irradiation differential regulate miRNAs expression in skin photoaging.

An Bras Dermatol 2022 May 31. Epub 2022 May 31.

Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Background: UVB irradiation can cause acute damage such as sunburn, or photoaging and melanoma, all of which are major health threats.

Objective: This study was designed to investigate the mechanism of skin photoaging induced by UVB radiation in mice through the analysis of the differential expression of miRNAs.

Methods: A UVB irradiation photoaging model was constructed. HE and Masson special stains were used to examine the modifications in the epidermis and dermis of mice. The miRNA expression profiles of the mouse skin model exposed to UVB radiation and the normal skin of mice were analyzed using miRNA-sequence analysis. GO and Pathway analysis were employed for the prediction of miRNA targets.

Results: A total of 23 miRNAs were evaluated for significantly different expressions in comparison to normal skin. Among them, 7 miRNAs were up-regulated and 16 were down-regulated in the skin with photoaging of mice exposed to UVB irradiation. The differential expression of miRNA is related to a variety of signal transduction pathways, among which mmu-miR-195a-5p and mitogen-activated protein kinase (MAPK) signal pathways are crucial. There was a significant differential expression of miRNA in the skin of normal mice in comparison with the skin with photoaging induced by UVB irradiation.

Study Limitations: Due to time and energy constraints, the specific protein level verification, MAPK pathway exploration, and miR-195a-5p downstream molecular mechanism need to be further studied in the future.

Conclusions: UVB-induced skin photoaging can be diagnosed and treated using miRNA.
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http://dx.doi.org/10.1016/j.abd.2022.01.003DOI Listing
May 2022

BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination.

Signal Transduct Target Ther 2022 Jun 1;7(1):170. Epub 2022 Jun 1.

Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, 211166, Nanjing, China.

Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1 mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe→ FN circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.
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http://dx.doi.org/10.1038/s41392-022-00989-xDOI Listing
June 2022

Decoding finger movement patterns from microscopic neural drive information based on deep learning.

Med Eng Phys 2022 06 9;104:103797. Epub 2022 Apr 9.

Department of Rehabilitation Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Recent development of surface electromyogram (sEMG) decomposition technique provides a good basis of decoding movements from individual motor unit (MU) activities that directly representing microscopic neural drives. How to interpret the function and contribution of each decomposed MU to macroscopic movements remains unclear. The objective of this study is to decode finger movement patterns by establishing a relationship between individual MU activities and movements. In this study, high-density sEMG (HD-sEMG) data were recorded by a 16 × 8 electrode array from finger extensor muscles of 10 subjects performing 10 finger movement patterns. The progressive FastICA peel-off algorithm was first applied to decompose the HD-sEMG data to obtain microscopic neural drives in terms of MU firing sequences and their corresponding action potential waveforms. Then, convolutional neural network was used for classification of the decomposed MUs by characterizing their spatial waveforms spanned over all channels of the array. On this basis, a fuzzy weighted decision strategy was designed to give a final decision of movement pattern recognition, where function of an individual MU was measured in the form of contributing into all movement patterns with different weights to solve the issue of MUs shared among multiple patterns due to muscle co-activation. The proposed method yielded an average accuracy approximating to 100%, and it outperformed other common MU-based methods or conventional myoelectric classification methods using macroscopic sEMG features (p <  0.05). The proposed method has a wide application prospect in the field of human-machine interaction and precise motor control.
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http://dx.doi.org/10.1016/j.medengphy.2022.103797DOI Listing
June 2022

IL-38 in modulating hyperlipidemia and its related cardiovascular diseases.

Int Immunopharmacol 2022 Jul 24;108:108876. Epub 2022 May 24.

Department of Cardiology, the Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian, China. Electronic address:

Hyperlipidemia is confirmed to be associated with several health problems that include the combination of diabetes mellitus, obesity, and hypertension, ie, metabolic syndrome. Although the lipid-lowering therapy is an effective treatment in hyperlipidemia and its related cardiovascular diseases (CVDs), the persistence of high atherosclerotic risk is notable which could not be simply explained as a phenomenon of hyperlipidemia. Concerning on this notion, it is imperative to identify novel biomarkers which could monitor treatment and predict adverse cardiovascular events. It is demonstrated that the chronic inflammatory response caused by immune cells is a characteristic of hyperlipidemia and atherosclerosis. Notably, among several inflammatory related cytokines, interleukin 38 (IL-38), as a member of the IL-1 family, plays an important role in anti-inflammatory response by binding with its receptor which inhibits the downstream signaling pathways. In addition, IL-38 suppresses the expression of inflammatory factors mainly through the mitogen-activated protein kinase (MAPK). At the cellular level, IL-38 could inhibit the CD4 positive T lymphocyte into T-helper 17 (Th-17) lymphocyte which further enhances the immunosuppressive activity of the T-regulatory lymphocyte (T-reg) to inhibit the inflammatory response. Consistently, IL-38 is shown to be strongly correlated to development of hyperlipidemic related CVDs. In this review, the roles of IL-38 in the development of hyperlipidemia are fully summarized. Furthermore, a theoretical basis for further in-depth research of IL-38 for treatment of hyperlipidemia is also provided.
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http://dx.doi.org/10.1016/j.intimp.2022.108876DOI Listing
July 2022

Mechanisms underlying immune-related adverse events during checkpoint immunotherapy.

Clin Sci (Lond) 2022 May;136(10):771-785

Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Immune checkpoint (IC) proteins are some of the most important factors that tumor cells hijack to escape immune surveillance, and inhibiting ICs to enhance or relieve antitumor immunity has been proven efficient in tumor treatment. Immune checkpoint blockade (ICB) agents such as antibodies blocking programmed death (PD) 1, PD-1 ligand (PD-L) 1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4 have been approved by the U.S. Food and Drug Administration (FDA) to treat several types of cancers. Although ICB agents have shown outstanding clinical success, and their application has continued to expand to additional tumor types in the past decade, immune-related adverse events (irAEs) have been observed in a wide range of patients who receive ICB treatment. Numerous studies have focused on the clinical manifestations and pathology of ICB-related irAEs, but the detailed mechanisms underlying irAEs remain largely unknown. Owing to the wide expression of IC molecules on distinct immune cell subpopulations and the fact that ICB agents generally affect IC-expressing cells, the influences of ICB agents on immune cells in irAEs need to be determined. Here, we discuss the expression and functions of IC proteins on distinct immune cells and the potential mechanism(s) related to ICB-targeted immune cell subsets in irAEs.
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http://dx.doi.org/10.1042/CS20210042DOI Listing
May 2022

The CD8α hinge is intrinsically disordered with a dynamic exchange that includes proline cis-trans isomerization.

J Magn Reson 2022 Jul 13;340:107234. Epub 2022 May 13.

Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Electronic address:

T cells engineered to express artificial chimeric antigen receptors (CARs) that selectively target tumor-specific antigens or deleterious cell types offer transformative therapeutic possibilities. CARs contain an N-terminal extracellular antigen recognition domain, C-terminal intracellular signal transduction domains, and connecting hinge and transmembrane regions, each of which have been varied to optimize targeting and minimize toxicity. We find that a CD22-targeting CAR harboring a CD8α hinge (H) exhibits greater cytotoxicity against a low antigen density CD22 leukemia as compared to an equivalent CAR with a CD28 H. We therefore studied the biophysical and dynamic properties of the CD8α H by nuclear magnetic resonance (NMR) spectroscopy. We find that a large region of the CD8α H undergoes dynamic chemical exchange between distinct and observable states. This exchanging region contains proline residues dispersed throughout the sequence that undergo cis-trans isomerization. Up to four signals of differing intensity are observed, with the most abundantly populated being intrinsically disordered and with all prolines in the trans isomerization state. The lesser populated states all contain cis prolines and evidence of local structural motifs. Altogether, our data suggest that the CD8α H lacks long-range structural order but has local structural motifs that transiently exchange with a dominant disordered state. We propose that structural plasticity and local structural motifs promoted by cis proline states within the CD8α H are important for relaying and amplifying antigen-binding effects to the transmembrane and signal transduction domains.
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http://dx.doi.org/10.1016/j.jmr.2022.107234DOI Listing
July 2022

Accumulation of Lipid Droplets in a Novel Bietti Crystalline Dystrophy Zebrafish Model With Impaired PPARα Pathway.

Invest Ophthalmol Vis Sci 2022 05;63(5):32

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Purpose: Bietti crystalline dystrophy (BCD) is a progressive retinal degenerative disease primarily characterized by numerous crystal-like deposits and degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. CYP4V2 (cytochrome P450 family 4 subfamily V member 2) is currently the only disease-causing gene for BCD. We aimed to generate a zebrafish model to explore the functional role of CYP4V2 in the development of BCD and identify potential therapeutic targets for future studies.

Methods: The cyp4v7 and cyp4v8 (homologous genes of CYP4V2) knockout zebrafish lines were generated by CRISPR/Cas9 technology. The morphology of photoreceptor and RPE cells and the accumulation of lipid droplets in RPE cells were investigated at a series of different developmental stages through histological analysis, immunofluorescence, and lipid staining. Transcriptome analysis was performed to investigate the changes in gene expression of RPE cells during the progression of BCD.

Results: Progressive retinal degeneration including RPE atrophy and photoreceptor loss was observed in the mutant zebrafish as early as seven months after fertilization. We also observed the excessive accumulation of lipid droplets in RPE cells from three months after fertilization, which preceded the retinal degeneration by several months. Transcriptome analysis suggested that multiple metabolism pathways, especially the lipid metabolism pathways, were significantly changed in RPE cells. The down-regulation of the peroxisome proliferator-activated receptor α (PPARα) pathway was further confirmed in the mutant zebrafish and CYP4V2-knockdown human RPE-1 cells.

Conclusions: Our work established an animal model that recapitulates the symptoms of BCD patients and revealed that abnormal lipid metabolism in RPE cells, probably caused by dysregulation of the PPARα pathway, might be the main and direct consequence of CYP4V2 deficiency. These findings will deepen our understanding of the pathogenesis of BCD and provide potential therapeutic approaches.
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http://dx.doi.org/10.1167/iovs.63.5.32DOI Listing
May 2022

Considerations for the Surgical Management of Thoracic Cancers During the COVID-19 Pandemic: Rational Strategies for Thoracic Surgeons.

Front Surg 2022 9;9:742007. Epub 2022 May 9.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: The novel Coronavirus Disease 2019 (COVID-19) has resulted in a global health crisis since first case was identified in December 2019. As the pandemic continues to strain global public health systems, elective surgeries for thoracic cancer, such as early-stage lung cancer and esophageal cancer (EC), have been postponed due to a shortage of medical resources and the risk of nosocomial transmission. This review is aimed to discuss the influence of COVID-19 on thoracic surgical practice, prevention of nosocomial transmission during the pandemic, and propose modifications to the standard practices in the surgical management of different thoracic cancer.

Methods: A literature search of PubMed, Medline, and Google Scholar was performed for articles focusing on COVID-19, early-stage lung cancer, and EC prior to 1 July 2021. The evidence from articles was combined with our data and experience.

Results: We review the challenges in the management of different thoracic cancer from the perspectives of thoracic surgeons and propose rational strategies for the diagnosis and treatment of early-stage lung cancer and EC during the COVID-19 pandemic.

Conclusions: During the COVID-19 pandemic, the optimization of hospital systems and medical resources is to fight against COVID-19. Indolent early lung cancers, such as pure ground-glass nodules/opacities (GGOs), can be postponed with a lower risk of progression, while selective surgeries of more biologically aggressive tumors should be prioritized. As for EC, we recommend immediate or prioritized surgeries for patients with stage Ib or more advanced stage and patients after neoadjuvant therapy. Routine COVID-19 screening should be performed preoperatively before thoracic surgeries. Prevention of nosocomial transmission by providing appropriate personal protective equipment (PPE), such as N-95 respirator masks with eye protection to healthcare workers, is necessary.
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http://dx.doi.org/10.3389/fsurg.2022.742007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124784PMC
May 2022

Long-term exposure to ambient black carbon is associated with sleep disturbance in college students.

Sci Total Environ 2022 Sep 20;838(Pt 2):156066. Epub 2022 May 20.

Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Background: Evidence suggests an association of air pollution with sleep quality. However, there is limited knowledge regarding the effect of black carbon, a key component of ambient particulate matter, on sleep.

Objectives: To investigate the association of long-term exposure to black carbon and sleep quality in a group of college students.

Methods: A retrospective cohort study was conducted in five universities in different regions of China. The concentrations of black carbon and other environment factors were defined as the averages during the 6 years prior to the recruitment. Averagely daily dose of black carbon exposure was estimated according to the respiratory rate. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) with a cutoff >5 indicating sleep disturbance. Linear regression and logistic regression models were used to estimate the association. The sensitivity analyses were conducted to estimate the effects of 1-month, 6-month and 1-year mean levels of exposure to black carbon on sleep quality.

Results: A total of 20,053 incoming college students were included. 29.3% reported impaired sleep quality, with a mean PSQI score of 4.3 ± 2.2. The logistic regression showed that the risk of impaired sleep quality was positively associated with black carbon exposure, especially in the highest quantile (OR: 1.26, 95% CI: 1.11-1.43) compared with the lowest quartile after adjusting for potential confounders. Subgroup analysis showed that the effect of black carbon on sleep quality was stronger in participants with higher BMI, lower household income, and lower parental educational level. The results of sensitivity analyses were similar with main analyses.

Conclusion: Long-term exposure to black carbon is associated with sleep disturbance in college students. Improvement of air quality may help improve sleep quality.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156066DOI Listing
September 2022

Acute lymphoblastic leukemia displays a distinct highly methylated genome.

Nat Cancer 2022 May 19. Epub 2022 May 19.

Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.

DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T cell ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients, which is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome and provide further insights into the non-canonical regulation of methylation in cancer.
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http://dx.doi.org/10.1038/s43018-022-00370-5DOI Listing
May 2022

The Multiple Biological Functions of Dipeptidyl Peptidase-4 in Bone Metabolism.

Front Endocrinol (Lausanne) 2022 2;13:856954. Epub 2022 May 2.

Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Dipeptidyl peptidase-4 (DPP4) is a ubiquitously occurring protease involved in various physiological and pathological processes ranging from glucose homeostasis, immunoregulation, inflammation to tumorigenesis. Recently, the benefits of DPP4 inhibitors as novel hypoglycemic agents on bone metabolism have attracted extensive attraction in many studies, indicating that DPP4 inhibitors may regulate bone homeostasis. The effects of DPP4 on bone metabolism are still unclear. This paper thoroughly reviews the potential mechanisms of DPP4 for interaction with adipokines, bone cells, bone immune cells, and cytokines in skeleton system. This literature review shows that the increased DPP4 activity may indirectly promote bone resorption and inhibit bone formation, increasing the risk of osteoporosis. Thus, bone metabolic balance can be improved by decreasing DPP4 activities. The substantial evidence collected and analyzed in this review supports this implication.
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http://dx.doi.org/10.3389/fendo.2022.856954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109619PMC
May 2022

Chemokine PF4 Inhibits EV71 and CA16 Infections at the Entry Stage.

J Virol 2022 Jun 17;96(11):e0043522. Epub 2022 May 17.

Center of Infectious Diseases and Pathogen Biology, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.

Platelet factor 4 (PF4) or the CXC chemokine CXCL4 is the most abundant protein within the α-granules of platelets. Previous studies found that PF4 regulates infections of several viruses, including HIV-1, H1N1, hepatitis C virus (HCV), and dengue virus. Here, we show that PF4 is an inhibitor of enterovirus A71 (EV71) and coxsackievirus A16 (CA16) infections. The secreted form of PF4 from transfected cells or soluble purified PF4 from Escherichia coli, even lacking signal peptide affected secretion, obviously inhibited the propagation of EV71 and CA16. Mechanistically, we demonstrated that PF4 blocked the entry of the virus into the host cells by interactions with VP3 proteins of EV71/CA16 and the interaction with SCARB2 receptor-mediated EV71 and CA16 endocytosis. As expected, the incubation of anti-PF4 antibody with PF4 blocked PF4 inhibition on EV71 and CA16 infections further supported the above conclusion. Importantly, pretreatment of EV71 viruses with PF4 significantly protected the neonatal mice from EV71 lethal challenge and promoted the survival rate of infected mice. PF4 derived from natural platelets by EV71/CA16 activation also presented strong inhibition on EV71 and CA16. In summary, our study identified a new host factor against EV71 and CA16 infections, providing a novel strategy for EV71 and CA16 treatment. The virus's life cycle starts with binding to cell surface receptors, resulting in receptor-mediated endocytosis. Targeting the entry of the virus into target cells is an effective strategy to develop a novel drug. EV71 and CA16 are the major pathogens that cause hand, foot, and mouth disease (HFMD) outbreaks worldwide since 2008. However, the treatment of EV71 and CA16 infections is mainly symptomatic because there is no approved drug. Therefore, the underlying pathogenesis of EV71/CA16 and the interaction between host-EV71/CA16 need to be further investigated to develop an inhibitor. Here, we identified PF4 as a potent entry inhibitor of EV71 and CA16 via binding to VP3 proteins of EV71 and CA16 or binding to receptor SCARB2. In the EV71 infection model, PF4 protected mice from EV71 lethal challenge and promoted the survival rate of EV71-infected mice. Our study suggests that PF4 represents a potential candidate host factor for anti-EV71 and CA16 infections.
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http://dx.doi.org/10.1128/jvi.00435-22DOI Listing
June 2022

The spatiotemporal dynamics of lung cancer: 30-year trends of epidemiology across 204 countries and territories.

BMC Public Health 2022 05 16;22(1):987. Epub 2022 May 16.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.

Background: It has been established that lung cancer is the leading cause of all cancer deaths. This study sought to analyze the epidemiological trends of lung cancer over the past 30 years worldwide.

Methods: Estimates, including the global, regional, national prevalence, incidence, and years lived with disability (YLDs) of lung cancer from 1990 to 2019, were extracted from the Global Burden of Disease Study 2019 to assess the spatiotemporal dynamics in cases and age-standardized rates (ASR). The estimated annual percentage change (EAPC) was calculated to evaluate the variation in ASR. Besides, estimates of age-sex specific prevalence, decomposition analysis for incident cases, and correlation analysis of the EAPC were conducted in our study.

Results: Globally, the ASR of lung cancer prevalence, incidence and YLDs in 2019 were 38.84/100,000 persons, 27.66/100,000 persons, and 6.62/100,000 persons, respectively. Over the past 30 years, the ASR of incidence (EAPC = -0.09) decreased, although that of prevalence (EAPC = 0.51) and YLDs (EAPC = 0.03) increased. The global prevalence counts was greater in males than females at all age groups and increased with age, peaking in the 65-69 age group for both sexes. The increase in incidence was mainly attributed to population aging. For YLDs, EAPC was negatively correlated with the human development index (p = 0.0008) and ASR (p < 0.0001) in 1990 across nation-level units.

Conclusions: Lung cancer remains a major public health issue globally, warranting the implementation of scientific and effective measures in different countries and territories to control it.
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http://dx.doi.org/10.1186/s12889-022-13281-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109351PMC
May 2022
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