Publications by authors named "Yue Chen"

2,049 Publications

  • Page 1 of 1

Metabolomic Approach for Rapid Identification of Antioxidants in Leaves with Liver Protective Potential.

Molecules 2022 Jun 7;27(12). Epub 2022 Jun 7.

Department of Bioscience, Faculty of Applied Sciences, Tunku Abdul Rahman University College, Setapak, Kuala Lumpur 53300, Malaysia.

Antioxidants are currently utilized to prevent the occurrence of liver cancer in non-alcoholic fatty liver disease (NAFLD) patients. possesses anti-oxidative and anti-inflammatory properties that could be an ideal therapy for liver problems. The objective of this study is to determine the potential antioxidative compounds from the leaves (CNL) and stems (CNS). Chemical- and cell-based antioxidative assays were utilized to evaluate the bioactivities of CNS and CNL. The NMR metabolomics approach assisted in the identification of contributing phytocompounds. Based on DPPH and ABTS radical scavenging activities, CNL demonstrated stronger radical scavenging potential as compared to CNS. The leaf extract also recorded slightly higher reducing power properties. A HepG2 cell model system was used to investigate the ROS reduction potential of these extracts. It was shown that cells treated with CNL and CNS reduced innate ROS levels as compared to untreated controls. Interestingly, cells pre-treated with both extracts were also able to decrease ROS levels in cells induced with oxidative stress. CNL was again the better antioxidant. According to multivariate data analysis of the H NMR results, the main metabolites postulated to contribute to the antioxidant and hepatoprotective abilities of leaves were clinacoside B, clinacoside C and isoschaftoside, which warrants further investigation.
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http://dx.doi.org/10.3390/molecules27123650DOI Listing
June 2022

Genome-Wide Analysis and Expression Profiling of the Phenylalanine Ammonia-Lyase Gene Family in .

Int J Mol Sci 2022 Jun 20;23(12). Epub 2022 Jun 20.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Agronomy, Northwest A&F University, Yangling 712100, China.

Phenylalanine ammonia-lyase is one of the most widely studied enzymes in the plant kingdom. It is a crucial pathway from primary metabolism to significant secondary phenylpropanoid metabolism in plants, and plays an essential role in plant growth, development, and stress defense. Although PAL has been studied in many actual plants, only one report has been reported on potato, one of the five primary staple foods in the world. In this study, 14 StPAL genes were identified in potato for the first time using a genome-wide bioinformatics analysis, and the expression patterns of these genes were further investigated using qRT-PCR. The results showed that the expressions of StPAL1, StPAL6, StPAL8, StPAL12, and StPAL13 were significantly up-regulated under drought and high temperature stress, indicating that they may be involved in the stress defense of potato against high temperature and drought. The expressions of StPAL1, StPAL2, and StPAL6 were significantly up-regulated after MeJa hormone treatment, indicating that these genes are involved in potato chemical defense mechanisms. These three stresses significantly inhibited the expression of StPAL7, StPAL10, and StPAL11, again proving that PAL is a multifunctional gene family, which may give plants resistance to multiple and different stresses. In the future, people may improve critical agronomic traits of crops by introducing other PAL genes. This study aims to deepen the understanding of the versatility of the PAL gene family and provide a valuable reference for further genetic improvement of the potato.
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http://dx.doi.org/10.3390/ijms23126833DOI Listing
June 2022

Melatonin Alleviates Oxidative Stress Induced by HO in Porcine Trophectoderm Cells.

Antioxidants (Basel) 2022 May 25;11(6). Epub 2022 May 25.

Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.

Placental oxidative stress has been implicated as a main risk factor for placental dysfunction. Alleviation of oxidative stress and enhancement of antioxidant capacity of porcine trophectoderm (PTr2) cells are effective means to maintaining normal placental function. The present study was conducted to evaluate the protective effect of melatonin (MT) on HO-induced oxidative damage in PTr2 cells. Our data revealed that pretreatment with MT could significantly improve the decrease in cell viability induced by HO, and reduce intracellular reactive oxygen species (ROS) levels and the ratio of apoptotic cells. Here, we compared the transcriptomes of untreated versus melatonin-treated PTr2 cells by RNA-seq analysis and found that differentially expressed genes (DEGs) were highly enriched in the Wnt signaling, TGF-beta signaling and mTOR signaling pathways. Moreover, pretreatment with MT upregulated the antioxidant-related genes such as early growth response3 (EGR3), WAP four-disulfide core domain1 (WFDC1), heme oxygenase1 (HMOX1) and vimentin (VIM). These findings reveal that melatonin protects PTr2 cells from HO-induced oxidative stress damage.
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http://dx.doi.org/10.3390/antiox11061047DOI Listing
May 2022

TEADs serve as potential prognostic biomarkers and targets for human gastric cancer.

BMC Gastroenterol 2022 Jun 24;22(1):308. Epub 2022 Jun 24.

Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, 211166, China.

TEADs are critical transcription factors that participate in the Hippo pathway. Evidence indicates the promotion role of TEADs in cancer progression. However, the role of TEADs and the expression patterns in gastric cancer remains unclear. In this study, we evaluated the expression levels of TEADs in gastric cancer samples, and the clinical outcomes of patients with high TEADs expression were observed. Co-expression and interaction analysis as well as functional enrichment analysis were further conducted to determine the potential role of TEADs in gastric cancer. These results suggested TEADs may serve as the prognostic biomarkers or therapeutic targets for gastric cancer. However, more studies are warranted to verify our findings and promote the application in gastric cancer patients.
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http://dx.doi.org/10.1186/s12876-022-02386-8DOI Listing
June 2022

Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.

NPJ Sci Food 2022 Jun 23;6(1):30. Epub 2022 Jun 23.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China.

Selenium (Se) is an essential micronutrient that promotes body health. Endemic Se deficiency is a major nutritional challenge worldwide. The low toxicity, high bioavailability, and unique properties of biogenic Se nanoparticles (SeNPs) allow them to be used as a therapeutic drug and Se nutritional supplement. This study was conducted to investigate the regulatory effects of dietary SeNPs supplementation on the oxidative stress-induced intestinal barrier dysfunction and its association with mitochondrial function and gut microbiota in mice. The effects of dietary SeNPs on intestinal barrier function and antioxidant capacity and its correlation with gut microbiota were further evaluated by a fecal microbiota transplantation experiment. The results showed that Se deficiency caused a redox imbalance, increased the levels of pro-inflammatory cytokines, altered the composition of the gut microbiota, and impaired mitochondrial structure and function, and intestinal barrier injury. Exogenous supplementation with biogenic SeNPs effectively alleviated diquat-induced intestinal barrier dysfunction by enhancing the antioxidant capacity, inhibiting the overproduction of reactive oxygen species (ROS), preventing the impairment of mitochondrial structure and function, regulating the immune response, maintaining intestinal microbiota homeostasis by regulating nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-mediated NLR family pyrin domain containing 3 (NLRP3) signaling pathway. In addition, Se deficiency resulted in a gut microbiota phenotype that is more susceptible to diquat-induced intestinal barrier dysfunction. Supranutritional SeNPs intake can optimize the gut microbiota to protect against intestinal dysfunctions. This study demonstrates that dietary supplementation of SeNPs can prevent oxidative stress-induced intestinal barrier dysfunction through its regulation of mitochondria and gut microbiota.
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http://dx.doi.org/10.1038/s41538-022-00145-3DOI Listing
June 2022

Bandgap Funneling in Bismuth-Based Hybrid Perovskite Photocatalyst with Efficient Visible-Light-Driven Hydrogen Evolution.

Small Methods 2022 Jun 22:e2200326. Epub 2022 Jun 22.

School of Energy and Environment, Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong, 999077, China.

The photocatalytic system using hydrohalic acid (HX) for hydrogen production is a promising strategy to generate clean and renewable fuels as well as value-added chemicals (such as X /X ). However, it is still challenging to develop a visible-light active and strong-acid resistive photocatalyst. Hybrid perovskites have been recognized as a potential photocatalyst for photovoltaic HX splitting. Herein, a novel environmentally friendly mixed halide perovskite MA Bi Cl I with a bandgap funnel structure is developed, i.e., confirmed by energy dispersive X-ray analysis and density functional theory calculations. Due to gradient neutral formation energy within iodine-doped MA Bi Cl , the concentration of iodide element decreases from the surface to the interior across the MA Bi Cl I perovskite. Because of the aligned energy levels of iodide/chloride-mixed MA Bi Cl I , a graded bandgap funnel structure is therefore formed, leading to the promotion of photoinduced charge transfer from the interior to the surface for efficient photocatalytic redox reaction. As a result, the hydrogen generation rate of the optimized MA Bi Cl I is enhanced up to ≈341 ± 61.7 µmol h with a Pt co-catalyst under visible light irradiation.
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http://dx.doi.org/10.1002/smtd.202200326DOI Listing
June 2022

A case of high-turnover renal osteodystrophy and vascular calcification in a patient with uremia diagnosed by F-NaF PET/CT.

Int Urol Nephrol 2022 Jun 22. Epub 2022 Jun 22.

Department of Nephrology, The Affiliated Hospital of Southwest Medical University, The 25th Taiping Street, Luzhou, 646000, Sichuan, China.

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http://dx.doi.org/10.1007/s11255-022-03275-5DOI Listing
June 2022

Application of Ga-citrate PET/CT for differentiating periprosthetic joint infection from aseptic loosening after joint replacement surgery.

Bone Joint Res 2022 Jun;11(6):398-408

Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Aims: We aimed to evaluate the utility of Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with Tc-methylene bisphosphonates (Tc-MDP) bone scan.

Methods: We studied 39 patients with suspected PJI or AL. These patients underwent Ga-citrate PET/CT, Tc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations.

Results: Overall, 23 and 16 patients were diagnosed with PJI and AL, respectively. The sensitivity and specificity of three-phase bone scan and SPECT/CT were 100% and 62.5%, 82.6%, and 100%, respectively. Attenuation correction (AC) at 60 minutes and non-AC at 60 minutes of PET/CT had the same highest sensitivity and specificity (91.3% and 100%), and AC at 60 minutes combined with SPECT/CT could improve the diagnostic efficiency (sensitivity = 95.7%). Diagnostic efficacy of the SUVmax was low (area under the curve (AUC) of ten minutes and 60 minutes was 0.814 and 0.806, respectively), and SUVmax of the lesion/SUVmean of the normal bone at 60 minutes was the best semi-quantitative parameter (AUC = 0.969).

Conclusion: Ga-citrate showed the potential to differentiate PJI from AL, and visual analysis based on uptake pattern of tracer was reliable. The visual analysis method of AC at 60 minutes, combined with Tc-MDP SPECT/CT, could improve the sensitivity from 91.3% to 95.7%. In addition, a major limitation of our study was that it had a limited sample size, and more detailed studies with a larger sample size are warranted. Cite this article:  2022;11(6):398-408.
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http://dx.doi.org/10.1302/2046-3758.116.BJR-2021-0464.R1DOI Listing
June 2022

Clonidine ameliorates cerebral ischemia-reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor.

Metab Brain Dis 2022 Jun 21. Epub 2022 Jun 21.

Third-Grade Pharmacological Laboratory On Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, People's Republic of China.

This study aimed to investigate the protective effects of the alpha-2 adrenergic receptor (α2-AR) agonist, clonidine, on the cerebral ischemia-reperfusion (I/R) injury and elaborate the underlying mechanisms. Cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 4 h in adult male SD rats. Saline, clonidine and yohimbine (an α2-AR antagonist) were intraperitoneally administered each day for one week before surgery. Neurological deficit was evaluated just before decapitation. TTC staining was applied for correlation of cerebral infarction volume. HE staining was performed to observe the neuron morphology. Immunohistochemical staining was performed to detect the localization and expression of GluN3 proteins. Western blot analysis also was used to detect the expression levels of GluN3 proteins. Our data showed that clonidine ameliorated neurological deficit and reduced the cerebral infarction volume of the rats with cerebral I/R. It is worth noting that treatment with clonidine up-regulated the protein expression of GluN3 in the rats with the cerebral I/R, especially in the cell membrane. Moreover, clonidine also up-regulated the transposition from cytoplasm to cell membrane of GluN3 after cerebral I/R. In addition, yohimbine abolished the neuroprotective effects of clonidine. The results indicated that clonidine played a protective role in cerebral I/R injury through regulation of the protein expression of GluN3 subunits of N-methyl-D-aspartate (NMDA) receptor.
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http://dx.doi.org/10.1007/s11011-022-01028-yDOI Listing
June 2022

Early Humoral Responses of Hemodialysis Patients After Inactivated SARS-CoV-2 Vaccination.

J Inflamm Res 2022 14;15:3467-3475. Epub 2022 Jun 14.

Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China.

Purpose: To detect antibody responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis and to investigate vaccine-related adverse events.

Patients And Methods: A total of 120 hemodialysis (HD) patients and 24 healthy controls (HCs) who had not been previously infected with SARS-CoV-2 and had received their first dose of the inactivated vaccine (CoronaVac; Sinovac Biotech Ltd) were recruited for this study. All participants were scheduled to receive a second dose of inactivated SARS-CoV-2 vaccine. Serum-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the SARS-CoV-2 were detected at least 14 days after the second dose of vaccine using a commercial kit. Positive and negative results were defined as a sample/cutoff (S/CO) ratio≥1.00 and <1.00, respectively. Vaccination-related adverse events were assessed using a standardized questionnaire.

Results: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and the self-reported vaccination-related adverse events between HD patients and HCs. The analysis results for HD patients suggest that 82 (68.3%) and 27 (22.5%) tested positive for IgG and IgM, respectively. The levels of IgG were higher than IgM levels (<0.0001). In addition, the IgG-positive group had significantly higher serum albumin levels than the IgG-negative group (<0.05). Only mild vaccine-related adverse events were observed in two patients (1.66%) and in one healthy individual (4.2%).

Conclusion: The seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar between HD and HCs. The inactivated SARS-CoV-2 vaccine is effective and safe in inducing near-term immunity in hemodialysis patients.
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http://dx.doi.org/10.2147/JIR.S361621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206439PMC
June 2022

Species-Specific Gene Expansion of the Gene Superfamily in the Orchidaceae Family and Functional Divergence of Mannan Synthesis-Related Genes in .

Front Plant Sci 2022 3;13:777332. Epub 2022 Jun 3.

Institute of Horticulture Research, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Plant genes constitute a supergene family that includes the (CesA) family and nine -like (Csl) families, the members of which are widely involved in the biosynthesis of cellulose and hemicellulose. However, little is known about the superfamily in the family Orchidaceae, one of the largest families of angiosperms. In the present study, we identified and systematically analyzed the family members in three fully sequenced Orchidaceae species, i.e., , , and . A total of 125 superfamily genes were identified in the three orchid species and classified into one CesA family and six Csl families: CslA, CslC, CslD, CslE, CslG, and CslH according to phylogenetic analysis involving nine representative plant species. We found species-specific expansion of certain gene families, such as the CslAs in (19 members). The families exhibited sequence divergence and conservation in terms of gene structure, phylogeny, and deduced protein sequence, indicating multiple origins via different evolutionary processes. The distribution of the genes was investigated, and 14 tandemly duplicated genes were detected, implying that the expansion of genes may have originated via gene duplication. Furthermore, the expression profiles of the genes were investigated using transcriptome sequencing and quantitative Real-time PCR (qRT-PCR) analysis, which revealed functional divergence in different tissues and during different developmental stages of . Three were highly expressed in the flower, whereas and family genes exhibited low expression levels in all tissues and at all developmental stages. The 19 were differentially expressed in the stems at different developmental stages, among which six were expressed at low levels or not at all. Notably, two ( and ) showed significantly high expression in the stems of , indicating a vital role in mannan synthesis. These results indicate the functional redundancy and specialization of with respect to polysaccharide accumulation. In conclusion, our results provide insights into the evolution, structure, and expression patterns of genes and provide a foundation for further gene functional analysis in Orchidaceae and other plant species.
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http://dx.doi.org/10.3389/fpls.2022.777332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204230PMC
June 2022

Design of a Bispecific HIV Entry Inhibitor Targeting the Cell Receptor CD4 and Viral Fusion Protein Gp41.

Front Cell Infect Microbiol 2022 27;12:916487. Epub 2022 May 27.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Given the high variability and drug-resistance problem by human immunodeficiency virus type 1 (HIV-1), the development of bispecific or multi-specific inhibitors targeting different steps of HIV entry is highly appreciated. We previously generated a very potent short-peptide-based HIV fusion inhibitor 2P23. In this study, we designed and characterized a bifunctional inhibitor termed 2P23-iMab by genetically conjugating 2P23 to the single-chain variable fragment (scFv) of ibalizumab (iMab), a newly approved antibody drug targeting the cell receptor CD4. As anticipated, 2P23-iMab could bind to the cell membrane through CD4 anchoring and inhibit HIV-1 infection as well as viral Env-mediated cell-cell fusion efficiently. When tested against a large panel of HIV-1 pseudoviruses with different subtypes and phenotypes, 2P23-iMab exhibited dramatically improved inhibitory activity than the parental inhibitors; especially, it potently inhibited the viruses not being susceptible to iMab. Moreover, 2P23-iMab had a dramatically increased potency in inhibiting two panels of HIV-1 mutants that are resistant to T-20 or 2P23 and the infections of HIV-2 and simian immunodeficiency virus (SIV). In conclusion, our studies have provided new insights into the design of novel bispecific HIV entry inhibitors with highly potent and broad-spectrum antiviral activity.
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http://dx.doi.org/10.3389/fcimb.2022.916487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197378PMC
June 2022

Probe Synthesis Reveals Eukaryotic Translation Elongation Factor 1 Alpha 1 as the Anti-Pancreatic Cancer Target of BE-43547A2.

Angew Chem Int Ed Engl 2022 Jun 15. Epub 2022 Jun 15.

Nankai University, College of Pharmacy, Weijin Road, Nankai district, 300071, Tianjin, CHINA.

The natural product, BE-43547A2, decreases pancreatic cancer cell stemness. However, its anticancer molecular mechanisms have not been fully established. Based on structure-activity relationships of BE-43547A2, we synthesized a probe and investigated its potential targets using an in situ click reaction. We found that BE-43547A2 exerts its anticancer effects by covalently binding the cysteine234 (C234) residue of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). This binding mode was confirmed by a series of experiments including a xenograft mouse model. We also determined that eEF1A1 plays an important role in regulating pancreatic cancer cell stemness. Analyses of 99 clinical pancreatic cancer samples revealed that eEF1A1 expressions are closely correlated with clinicopathological grade and patient survival. In conclusion, eEF1A1 is involved in pancreatic cancer progression and is therefore, a promising novel covalent target for pancreatic cancer treatment.
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http://dx.doi.org/10.1002/anie.202206953DOI Listing
June 2022

Modulation of Electrical and Thermal Transports through Lattice Distortion in BaTiNbOSolid Solutions.

Nanotechnology 2022 Jun 15. Epub 2022 Jun 15.

Research Institute for Electronic Science, Hokkaido University, N20W10, Kita, Sapporo, Hokkaido, 001-0020, JAPAN.

The electron and heat transports in solids are through the movement of carrier electrons and quantized lattice vibrations (phonons), which are sensitive to the lattice distortion and ionized impurities, and are essential aspects for the development of novel thermoelectric materials. In this study, we systematically investigated the modulations of electrical and thermal conductivities of BaTiNbOsolid solution (BTNO, 0 ≦≦ 1) epitaxial films. At room temperature, BaTiObelongs to tetragonal perovskite and exhibits electron conduction through doubly degenerated Ti 3d-torbitals upon doping, while BaNbObelongs to cubic perovskite and exhibits metallic electron conduction through partially filled triply degenerate Nb 4d-torbitals. By controlling the Ti/Nb ratio, we found a dual modulation effect on both the lattice structures and conduction band, which affects the electrical and thermal conductivities. Similar to the SrTiNbOsolid solution (STNO, 0 ≦≦ 1) system, a phase transition was detected at~ 0.5, at which both the electron and heat transports exhibit abrupt changes. Unlike the transition in STNO, which was attributed to a polaronic phase transition, the transition in BTNO was due to contributions from both the lattice distortion and polaron effect. By controlling the lattice distortion, conduction band, and polaronic phase transitions, the electrical and thermal conductivity of BTNO epitaxial films are modulated within a much greater range than those of the STNO epitaxial films. Due to the double contribution of electron carriers and phonon to thermal conductivity (), the maximummodulation ratio of BTNO epitaxial films was ~6.9. Our research provides an effective route to design electrical/thermal management materials.
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http://dx.doi.org/10.1088/1361-6528/ac78f3DOI Listing
June 2022

CXCL13 expression in mouse 4T1 breast cancer microenvironment elicits antitumor immune response by regulating immune cell infiltration.

Precis Clin Med 2021 Sep 4;4(3):155-167. Epub 2021 Aug 4.

Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, and Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related deaths among women worldwide. Previous studies have reported contradictory performance of chemokine CXC motif ligand 13 (CXCL13) in breast cancer. In this study, The Cancer Genome Atlas database analysis revealed that CXCL13 was overexpressed in various human cancers including breast carcinoma, and associated with good clinical prognosis in breast cancer. Flow cytometry detection also found upregulated intracellular CXCL13 expression in human breast cancer cell lines. To explore the possible role of CXCL13 in the breast cancer microenvironment, mouse triple negative breast cancer (TNBC) was lentivirally transfected to stably overexpress mouse CXCL13 (4T1-CXCL13). Both parental 4T1 and 4T1-CXCL13 strains showed no or endogenous cell surface CXCR5 expression. In immune-competent BALB/c mice, the tumor growth of 4T1-CXCL13 was significantly inhibited and even completely eradicated, accompanied with increased infiltrations of CD4, CD8 T lymphocytes and CD11bCD11c DCs. Further investigations showed that CXCL13 expression in the 4T1 tumor microenvironment elicited long-term antitumor immune memory, and rejection of distal parental tumor. The antitumor activity of CXCL13 was remarkedly impaired in BALB/cA-nu nude mice, or in BALB/c mice with CD8 T lymphocyte or NK cell depletion. Our investigation indicated that CXCL13 expression in TNBC triggered effective antitumor immunity by chemoattracting immune cell infiltrations and could be considered as a novel prognostic marker for TNBC.
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http://dx.doi.org/10.1093/pcmedi/pbab020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982548PMC
September 2021

The antioxidant activities, inhibitory effects, kinetics, and mechanisms of artocarpin and α-mangostin on α-glucosidase and α-amylase.

Int J Biol Macromol 2022 Jul 8;213:880-891. Epub 2022 Jun 8.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address:

This study investigated the antioxidant activities, enzyme inhibitory activities and the interaction mechanisms of artocarpin and α-mangostin on α-amylase and α-glucosidase. Results showed that artocarpin and α-mangostin had obvious antioxidant activities and inhibitory activities on α-glucosidase and α-amylase. The inhibitions of the two compounds on α-glucosidase were reversible and non-competitive according to the kinetics studies. Fluorescence intensity measurements indicated that the interaction mechanisms between the inhibitors and the two enzymes were static processes. Isothermal titration calorimetry (ITC) analysis showed that the bindings between the inhibitors and the enzymes complex were all spontaneous. The main driving forces between α-mangostin and artocarpin with α-glucosidase might be hydrogen bonds and electrostatic interactions, respectively. While the forces between the two inhibitors and α-amylase might be hydrophobic interactions. Furthermore, molecular docking results showed that artocarpin and α-mangostin could bind to the allosteric site of the two enzymes, except for artocarpin in the active site pocket of α-amylase. All the results indicated that artocarpin and α-mangostin might be promising candidates for hypoglycemic functional products.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.017DOI Listing
July 2022

Higher Mean Arterial Pressure during Cardiopulmonary Bypass May Not Prevent Acute Kidney Injury in Elderly Patients Undergoing Cardiac Surgery.

Int J Clin Pract 2022 14;2022:7701947. Epub 2022 Apr 14.

Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.

We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI). . We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. . Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group ( < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI ( = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI ( = 0.034). . A higher MAP in the range of 65-75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.
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http://dx.doi.org/10.1155/2022/7701947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159145PMC
June 2022

A Review of Village Ecosystem Vulnerability and Resilience: Implications for the Rocky Desertification Control.

Int J Environ Res Public Health 2022 May 30;19(11). Epub 2022 May 30.

School of Karst Science, Guizhou Normal University, Guiyang 550001, China.

Under the background of global environmental change, a huge impact has been made on the village ecosystem, which leads to disorder of structure and function of the village ecosystem. The current management measures of the village have failed in allowing the village to achieve sustainable development. Research on the vulnerability and resilience of the village ecosystem is helpful in regards to the ecological restoration of the village. The research status and progress in regards to the vulnerability and resilience of the village ecosystem are not clear, and the summary of research results and problems is insufficient. Based on 87 related literatures, this paper focuses on the current status and progress of village ecosystem vulnerability and resilience research, and reveals the current research results and shortcomings of village ecosystem vulnerability and resilience. We found that: (1) the research on vulnerability and resilience of the village ecosystem is on the rise; (2) the research mainly focuses on the index system, monitoring and assessment, mechanism research and strategy research. The monitoring and assessment research is the most prominent, which mainly discusses the research methods, the vulnerability and the resilience of the village ecosystem; (3) the study area is mainly concentrated in Asia, North America and Africa. Research institutions are mainly institutions of higher learning and research institutes (centers). Finally, this paper finds that major scientific and technical studies such as the construction of indicator systems and the study of governance strategies in the study of vulnerability and resilience of village ecosystems are lagging behind. In future research, we should deepen the research on the concept and connotation of vulnerability and resilience. We must establish a scientific and reasonable research framework for vulnerability and resilience of the village ecosystem. We should also strengthen and improve the index system of vulnerability and resilience of the village ecosystem. We should strengthen research on the impact mechanisms and governance strategies of vulnerability and resilience, and apply the research on vulnerability and resilience to the planning and governance of the village ecosystem.
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http://dx.doi.org/10.3390/ijerph19116664DOI Listing
May 2022

A visual knowledge map analysis of mine fire research based on CiteSpace.

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

School of Emergency Management and Safety Engineering, China University of Mining and Technology (Beijing), Beijing, 100083, China.

Mine fire has always been a serious disaster in coal industry; many academic achievements have poured out in the past two decades for solving this problem. In this study, visual analysis was conducted to grasp the hotspots and development trend of mine fire research. Papers that published in 1999-2020 were retrieved as the data basis from Web of Science, and CiteSpace was used to carry out knowledge map analysis. The results shown that number of papers has increased steadily since 2005 and achieved explosive growth since 2014. Deng J is the first published author among many scholars. China, the USA, and Australia are active areas in mine fire research and China University of Mining and Technology ranks first in this field. The highest co-occurrence frequency keyword is "spontaneous combustion." International Journal of Coal Geology and Fuel provide guidance for mine fire research. Fire prevention technology, low carbon, ecology, and sustainable development are the hot research in recent years. The prevention and control of mine fire from combustion mechanism should be further strengthened.
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http://dx.doi.org/10.1007/s11356-022-20993-6DOI Listing
June 2022

Characteristics and Predictors of Venous Thromboembolism Among Lymphoma Patients Undergoing Chemotherapy: A Cohort Study in China.

Front Pharmacol 2022 23;13:901887. Epub 2022 May 23.

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.

Venous thromboembolism (VTE) is a potential complication among lymphoma patients. We evaluated the incidence rate and predictors of VTE in lymphoma patients undergoing chemotherapy. The present study retrospectively studied 1,069 patients with lymphoma who were treated with chemotherapy from 2018 to 2020. We investigated clinical predictors of VTE among all patients. The follow-up results were obtained telephone communication and from inpatient and outpatient records. A total of 1,069 patients underwent chemotherapy for lymphoma. During a mean follow-up of 23.1 months, 52 (4.9%) patients developed VTE. According to a multivariate analysis, the five variables found to be independently associated with VTE were male sex (HR 2.273, 95% CI 1.197-4.316, = 0.012), age >64-years-old (HR 2.256, 95% CI 1.017-5.005, = 0.045), the number of cycles of chemotherapy (HR 4.579, 95% CI 1.173-17.883, = 0.029), platelet count ≥350 × 10/L (HR 2.533, 95% CI 1.187-5.406, = 0.016), and D-dimer >0.5 mg/L (HR 4.367, 95% CI 2.124-8.981, < 0.001). This population-based study confirms the risk factors for VTE among patients with lymphoma who underwent chemotherapy and confirms that targeted thromboprophylaxis may reduce the burden of VTE in this population.
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http://dx.doi.org/10.3389/fphar.2022.901887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168459PMC
May 2022

Use of deep learning-based radiomics to differentiate Parkinson's disease patients from normal controls: a study based on [F]FDG PET imaging.

Eur Radiol 2022 Jun 8. Epub 2022 Jun 8.

Institute of Biomedical Engineering, School of Communication and Information Engineering, Shanghai University, Shanghai, 200444, China.

Objectives: We proposed a novel deep learning-based radiomics (DLR) model to diagnose Parkinson's disease (PD) based on [F]fluorodeoxyglucose (FDG) PET images.

Methods: In this two-center study, 255 normal controls (NCs) and 103 PD patients were enrolled from Huashan Hospital, China; 26 NCs and 22 PD patients were enrolled as a separate test group from Wuxi 904 Hospital, China. The proposed DLR model consisted of a convolutional neural network-based feature encoder and a support vector machine (SVM) model-based classifier. The DLR model was trained and validated in the Huashan cohort and tested in the Wuxi cohort, and accuracy, sensitivity, specificity and receiver operator characteristic (ROC) curve graphs were used to describe the model's performance. Comparative experiments were performed based on four other models including the scale model, radiomics model, standard uptake value ratio (SUVR) model and DLR model.

Results: The DLR model demonstrated superiority in differentiating PD patients and NCs in comparison to other models, with an accuracy of 95.17% [90.35%, 98.13%] (95% confidence intervals, CI) in the Huashan cohort. Moreover, the DLR model also demonstrated greater performance in diagnosing PD early than routine methods, with an accuracy of 85.58% [78.60%, 91.57%] in the Huashan cohort.

Conclusions: We developed a DLR model based on [F]FDG PET images that showed good performance in the noninvasive, individualized prediction of PD and was superior to traditional handcrafted methods. This model has the potential to guide and facilitate clinical diagnosis and contribute to the development of precision treatment.

Key Points: The DLR method on [F]FDG PET images helps clinicians to diagnose PD and PD subgroups from normal controls. A prospective two-center study showed that the DLR method provides greater diagnostic accuracy.
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http://dx.doi.org/10.1007/s00330-022-08799-zDOI Listing
June 2022

Perfluoroalkyl substances in the surface water and fishes in Chaohu Lake, China.

Environ Sci Pollut Res Int 2022 Jun 4. Epub 2022 Jun 4.

School of Environmental Science and Engineering, Chang'An University, Xi'an 710064, China.

The concentration and composition of 13 perfluoroalkyl substances (PFASs) in surface water and fishes in Chaohu Lake, China, were systematically studied in October 2019. Results showed that the PFASs composition has changed greatly. The concentration levels of perfluorooctane sulfonate (PFOS) in the surface water of Chaohu Lake have decreased significantly compared with past years. Perfluorobutanoic acid (PFBA) has become the dominant component, and it was mainly come from industrial wastewater. The highest concentration of perfluorooctanoic acid (PFOA) was measured in the lake inlet of the Baishitian River (southwest part), which mainly received domestic sewage. Different types of wastewater lead to varying compositions of PFASs in the lake water. PFOA and PFBS were homologous in some areas of Chaohu Lake, which reflected the unbalanced promotion of prohibition and substitution of long-chain PFASs around Chaohu Lake. On the basis of the risk quotient and tolerable daily intake assessment, drinking water and eating fish from Chaohu Lake do not lead to apparent PFAS risk, but PFOS in fish has evident bioaccumulation and biomagnification effects. PFOS-based human daily intake of Channa argus accounts for 22.4% of the tolerable daily intake. Thus, the risk caused by PFOS needs close attention. This study is useful for enhancing people's understanding of the environmental behavior and the risk of PFASs in Chaohu Lake.
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http://dx.doi.org/10.1007/s11356-022-20753-6DOI Listing
June 2022

Mechanisms of ductular reaction in non-alcoholic steatohepatitis.

World J Gastroenterol 2022 May;28(19):2088-2099

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.

Non-alcoholic fatty liver disease (NAFLD) is a disease spectrum caused in part by insulin resistance and genetic predisposition. This disease is primarily characterized by excessive lipid accumulation in hepatocytes in the absence of alcohol abuse and other causes of liver damage. Histologically, NAFLD is divided into several periods: simple steatosis, non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. With the increasing prevalence of obesity and hyperlipidemia, NAFLD has become the main cause of chronic liver disease worldwide. As a result, the pathogenesis of this disease is drawing increasing attention. Ductular reaction (DR) is a reactive bile duct hyperplasia caused by liver injury that involves hepatocytes, cholangiocytes, and hepatic progenitor cells. Recently, DR is shown to play a pivotal role in simple steatosis progression to NASH or liver fibrosis, providing new research and treatment options. This study reviews several DR signaling pathways, including Notch, Hippo/YAP-TAZ, Wnt/β-catenin, Hedgehog, HGF/c-Met, and TWEAK/Fn14, and their role in the occurrence and development of NASH.
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http://dx.doi.org/10.3748/wjg.v28.i19.2088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134136PMC
May 2022

Pristine PN junction toward atomic layer devices.

Light Sci Appl 2022 Jun 6;11(1):170. Epub 2022 Jun 6.

State Key Laboratory of Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai, 200083, China.

In semiconductor manufacturing, PN junction is formed by introducing dopants to activate neighboring electron and hole conductance. To avoid structural distortion and failure, it generally requires the foreign dopants localize in the designated micro-areas. This, however, is challenging due to an inevitable interdiffusion process. Here we report a brand-new junction architecture, called "layer PN junction", that might break through such limit and help redefine the semiconductor device architecture. Different from all existing semiconductors, we find that a variety of van der Waals materials are doping themselves from n- to p-type conductance with an increasing/decreasing layer-number. It means the capability of constructing homogeneous PN junctions in monolayers' dimension/precision, with record high rectification-ratio (>10) and low cut-off current (<1 pA). More importantly, it spawns intriguing functionalities, like gate-switchable-rectification and noise-signal decoupled avalanching. Findings disclosed here might open up a path to develop novel nanodevice applications, where the geometrical size becomes the only critical factor in tuning charge-carrier distribution and thus functionality.
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http://dx.doi.org/10.1038/s41377-022-00814-8DOI Listing
June 2022

DEC1 represses cardiomyocyte hypertrophy by recruiting PRP19 as an E3 ligase to promote ubiquitination-proteasome-mediated degradation of GATA4.

J Mol Cell Cardiol 2022 May 31;169:96-110. Epub 2022 May 31.

Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; NHC Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Although the pro-hypertrophic role of GATA binding protein 4 (GATA4) during cardiac hypertrophy has been well established, the negative regulatory mechanism to counteract its hyperactivation remains elusive. We hypothesized that the hyperactivation of GATA4 could be a result of loss of interaction between GATA4 with specific suppressors. Using high throughput mass spectrometry technology, we carried out a proteomic screen for endogenous suppressor of GATA4, which disassociated with GATA4 during the hypertrophic response in a cultured cardiac myoblast cell line (H9C2 cells). We identified differentiated embryo chondrocyte 1 (DEC1) negatively regulated the function of GATA4 through physical interaction and negatively regulated cardiac hypertrophy both in vivo and in vitro. Particularly, DEC1 promoted the ubiquitination and proteasome-mediated degradation of GATA4, but did not function as an E3 ligase. Again, using mass spectrometry technology, we systematically identified pre-mRNA processing factor 19 (PRP19) as a newfound E3 ligase, which promoted the K6-linked ubiquitination of GATA4 at its lysine 256. Functional experiments performed in cultured neonatal rat ventricular myocytes and H9C2 cells demonstrated that both DEC1 and PRP19 negatively regulated agonist-induced cardiomyocyte hypertrophic responses. Furthermore, rescue experiments performed in these cells revealed that DEC1 and PRP19 suppressed cardiomyocyte hypertrophy by inhibiting the function of GATA4. Our study thus defined the novel DEC1-PRP19-GATA4 axis to be a previously unknown mechanism in regulating cardiomyocyte hypertrophy. Although GATA4 is indispensable for normal cardiac function, harnessing DEC1- or PRP19-mediated negative regulation to counteract the hyperactivation of GATA4 might serve as a novel therapeutic strategy for pathological cardiac hypertrophy.
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http://dx.doi.org/10.1016/j.yjmcc.2022.05.005DOI Listing
May 2022

Humic Substances Derived From Biomass Waste During Aerobic Composting and Hydrothermal Treatment: A Review.

Front Bioeng Biotechnol 2022 12;10:878686. Epub 2022 May 12.

Department of Biology, Institute of Bioresource and Agriculture, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

Humic substances (HSs) occupy 80% of organic matter in soil and have been widely applied for soil remediation agents, potential battery materials, and adsorbents. Since the HS extraction rate is very low by microbial degradation in nature, artificial humification processes such as aerobic composting (AC) and hydrothermal treatment (HT) have attracted a great deal of attention as the most important strategies in HS production. This article aims to provide a state-of-the-art review on the development of conversion of biomass waste into HSs based on AC and HT for the first time in terms of mechanisms, characteristics of HSs' molecular structure, and influencing factors. In addition, some differences based on the aforementioned information between AC and HT are reviewed and discussed in the conversion of biomass waste into HSs in a pioneering way. For biomass waste conversion, a feasible strategy on effective humification processes by combining AC with HT is proposed.
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http://dx.doi.org/10.3389/fbioe.2022.878686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133812PMC
May 2022

The effects of mismatch between SPECT and CT images on quantitative activity estimation - A simulation study.

Z Med Phys 2022 May 26. Epub 2022 May 26.

Biomedical Imaging Laboratory (BIG), Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Taipa, Macau SAR, China; Center for Cognitive and Brain Sciences, Institute of Collaborative Innovation, University of Macau, Taipa, Macau SAR, China; Ministry of Education Frontiers Science Center for Precision Oncology, Faculty of Health Science, University of Macau, Taipa, Macau SAR, China. Electronic address:

Background: Quantitative activity estimation is essential in nuclear medicine imaging. Mismatch between SPECT and CT images at the same imaging time point due to patient movement degrades accuracy in both diagnostic studies and target radionuclide therapy dosimetry. This work aims to study the mismatch effects between CT and SPECT data on attenuation correction (AC), volume-of-interest (VOI) delineation, and registration for activity estimation.

Methods: Nine 4D XCAT phantoms were generated at 1, 24, and 144 h post In-111 Zevalin injection, varying in activity distributions, body sizes, and organ sizes. Realistic noisy SPECT projections were generated by an analytical projector and reconstructed with a quantitative OS-EM method. CT images were shifted, corresponding to SPECT images at each imaging time point, from -5 to 5 voxels and also according to a clinical reference. The effect of mismatched AC maps was evaluated using mismatched CT images for AC in SPECT reconstruction while VOIs were mapped out from matched CTs. The effect of mismatched VOI drawings was evaluated using mismatched CTs to map out target organs while using matched CTs for AC. The effect of mismatched CT images for registration was evaluated by registering sequential mismatched CTs to align corresponding SPECT images, with no AC and VOI mismatch. Bi-exponential curve fitting was performed to obtain time-integrated activity (TIA). Organ activity errors (%OAE) and TIA errors (%TIAE) were calculated.

Results: According to the clinical reference, %OAE was larger for organs near ribs for AC effect. For VOI effect, %OAE was larger for small and low uptake organs. For registration effect, %TIAE were larger when mismatch existed in more numbers of SPECT/CT images, while no substantial difference was observed when using mismatched CT at different imaging time points as registration reference. %TIAE was highest for VOI, followed by registration and AC, e.g., 20.62%±8.61%, 9.33%±4.66% and 1.13%±0.90% respectively for kidneys.

Conclusions: The mismatch between CT and SPECT images poses a significant impact on the accuracy of quantitative activity estimation, attributed particularly from VOI delineation errors. It is recommended to perform registration between emission and transmission images at the same time point to ensure diagnostic and dosimetric accuracy.
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http://dx.doi.org/10.1016/j.zemedi.2022.03.004DOI Listing
May 2022

Hypogyrification in Generalized Anxiety Disorder and Associated with Insomnia Symptoms.

Nat Sci Sleep 2022 25;14:1009-1019. Epub 2022 May 25.

Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, Anhui Province, People's Republic of China.

Purpose: Insomnia is a recognized feature of generalized anxiety disorder (GAD). The underlying neural substrate of insomnia in GAD is still unclear. Cortical folding is a reliable index and possibly an endophenotype of psychiatric disease. The aim of this study was to explore whether the aberrant cortical morphology was associated with insomnia in GAD.

Patients And Methods: We enrolled 73 patients with GAD and 74 matched healthy controls (HCs) to undergo neuropsychiatric assessment and 3.0 T magnetic resonance imaging scanning. Neuropsychiatric batteries included the 14-item Hamilton Anxiety Rating Scale (HAMA) and the Insomnia Severity Index (ISI). Using FreeSurfer7.1.1, we calculated local gyrification index, cortical thickness and surface area and identified group differences in these parameters. Then, we calculated the functional connectivity of these identified regions and determined functional alterations. The relationship between these neuroimaging indicators and clinical measurement was explored.

Results: Compared with HCs, the LGI in the bilateral orbitofrontal cortex (OFC), bilateral insula, left middle frontal gyrus, left temporal pole, and left fusiform area was significantly decreased in GAD. GAD patients had concurrent decreased surface area in the left OFC and thicker right OFC. GAD patients also exhibited increased functional connectivity between the left insula and frontoparietal control network. In addition, a negative relationship was observed between decreased LGI in these limbic regions and ISI score.

Conclusion: GAD patients presented aberrant cortical folding in limbic network. Cortical morphology is a potential endophenotype in GAD, corresponding to an insomnia phenotype.
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http://dx.doi.org/10.2147/NSS.S358763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148579PMC
May 2022

Association of Daily Exposure to Air Pollutants with the Risk of Tuberculosis in Xuhui District of Shanghai, China.

Int J Environ Res Public Health 2022 05 17;19(10). Epub 2022 May 17.

School of Public Health, Fudan University, Building 8, 130 Dong'an Road, Shanghai 200032, China.

Previous studies have suggested that air pollutant exposure is related to tuberculosis (TB) risk, but results have not been consistent. This study evaluated the relation between daily air pollutant exposure and TB incidence in Shanghai from 2014 to 2019. Overall, there were four pollutants that were positively related to the risk of new TB cases. After a 5 μg/m increase, the maximum lag-specific and cumulative relative risk (RR) of SO were 1.081, (95% CI: 1.035-1.129, lag: 3 days) and 1.616 (95% CI: 1.119-2.333, lag: 0-13 days), while for NO, they were 1.061 (95% CI: 1.015-1.11, lag: 4 days) and 1.8 (95% CI: 1.113-2.91, lag: 0-15 days). As for PM, with a 50 μg/m increase, the lag-specific and cumulative RR were 1.064 (95% CI: 1-1.132, lag: 6 days) and 3.101 (95% CI: 1.096-8.777, lag: 0-21 days), while for CO, the lag-specific RR was 1.03 (95% CI: 1.005-1.057, lag: 8 days) and the cumulative RR was 1.436 (95% CI: 1.004-2.053, lag: 0-16 days) with a 100 μg/m increase. The associations tended to be stronger in male and elderly patients and differed with seasons. Air pollutant exposure may be a risk factor for TB incidence.
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http://dx.doi.org/10.3390/ijerph19106085DOI Listing
May 2022

Lenvatinib Plus Pembrolizumab vs. Chemotherapy in Pretreated Patients With Advanced Endometrial Cancer: A Cost-Effectiveness Analysis.

Front Public Health 2022 10;10:881034. Epub 2022 May 10.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Background: In the international, randomized, open-label, phase 3 study 309-KEYNOTE-775 trial, lenvatinib plus pembrolizumab (LP) showed improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in pretreated patients with advanced endometrial cancer. This study aimed to investigate whether LP is cost-effective compared with chemotherapy.

Materials And Methods: The clinical data for this model was derived from the 309-KEYNOTE-775 trial. Costs and utilities were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced endometrial cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether LP is cost-effective in patients with mismatch repair-proficient (pMMR) disease.

Results: Lenvatinib plus pembrolizumab provided an incremental 0.64 quality-adjusted life years (QALYs) with an incremental cost of $241,278.18, compared with chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $378,251.44/QALY, which exceeded the willingness to pay (WTP) threshold. While in the pMMR subgroup, the ICER increased to $413,256.68/QALY. The variance of the utility of PFS state, the cost of LP, and the utility of the progressive disease state were the most influential factors in the sensitivity analysis.

Conclusion: Under the current WTP threshold, LP is not cost-effective compared with chemotherapy in pretreated patients with advanced endometrial cancer.
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http://dx.doi.org/10.3389/fpubh.2022.881034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127138PMC
May 2022
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