Publications by authors named "Lin Yang"

2,960 Publications

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Persistent Purine Metabolic Abnormality Induces the Aggravation of Visceral Inflammation and Intestinal Microbiota Dysbiosis in Magang Goose.

Front Vet Sci 2021 6;8:737160. Epub 2021 Sep 6.

Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China.

Gout is a disease involving abnormal purine metabolism that is widespread in mammals and birds. Goose is especially susceptible for gout in early stage. However, a few studies investigated the ontogenetic pattern of goslings with purine metabolic abnormality. Our studies were conducted to investigate whether persistent purine metabolic abnormality would lead to aggravation of visceral inflammation and intestinal microbiota dysbiosis in goose. A total of 132 1-day-old Magang geese were randomly divided into six replicates and fed a high-calcium and protein meal-based diet from 1 to 28 days. The experiment lasted for 28 days. Liver and kidney damages were observed in 14- and 28-day-old Magang geese, and liver inflammation increased with increasing age. In 28-day-old Magang geese, serum CAT and liver GSH-Px activity were significantly reduced. Furthermore, jejunum intestinal barrier was impaired and the abundance of was significantly reduced at the genus level. Collectively, the high-calcium and high-protein (HCP) meal-based diet caused liver and kidney damage in 28-day-old Magang geese, leading to hyperuricemia and gout symptoms, and the intestinal barrier is impaired and the intestinal flora is disrupted.
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http://dx.doi.org/10.3389/fvets.2021.737160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452157PMC
September 2021

Highly accurate diagnosis of lung adenocarcinoma and squamous cell carcinoma tissues by deep learning.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 14;265:120400. Epub 2021 Sep 14.

State Key Laboratory of Tribology, Tsinghua University, Beijing 100084, China.

Intraoperative detection of the marginal tissues is the last and most important step to complete the resection of adenocarcinoma and squamous cell carcinoma. However, the current intraoperative diagnosis is time-consuming and requires numerous steps including staining. In this paper, we present the use of Raman spectroscopy with deep learning to achieve accurate diagnosis with stain-free process. To make the spectrum more suitable for deep learning, we utilize an unusual way of thinking which regards Raman spectral signal as a sequence and then converts it into two-dimensional Raman spectrogram by short-time Fourier transform as input. The normal-adenocarcinoma deep learning model and normal-squamous carcinoma deep learning model both achieve more than 96% accuracy, 95% sensitivity and 98% specificity when test, which higher than the conventional principal components analysis-linear discriminant analysis method with normal-adenocarcinoma model (0.896 accuracy, 0.867 sensitivity, 0.926 specificity) and normal-squamous carcinoma model (0.821 accuracy, 0.776 sensitivity, 1.000 specificity). The high performance of deep learning models provides a reliable way for intraoperative detection of marginal tissue, and is expected to reduce the detection time and save human lives.
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http://dx.doi.org/10.1016/j.saa.2021.120400DOI Listing
September 2021

Robust one-pot multi-enzyme polysaccharide remodeling strategy for the synthesis of uniform chondroitin fragments and derivatives.

Carbohydr Res 2021 Sep 16;509:108442. Epub 2021 Sep 16.

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, Shandong, 266237, People's Republic of China. Electronic address:

The non-sulfated chondroitin backbone (CH) is the synthetic precursor of chondroitin sulfate, a linear polysaccharide with dramatic biological functions. Owing to the intrinsic characteristics of the polysaccharide biosynthetic pathway, it is still a challenge to obtain structural-defined glycans via microbial fermentation or enzymatic synthesis, which hindering the illustration of CH polysaccharide functions. Herein, we report a robust one-pot multi-enzyme polysaccharide remodeling strategy to synthesize uniform CH fragments and their derivatives. CH tetrasaccharide, which was obtained from the digestion of heterogeneous CH fragments, was used as the starting material to trigger the assembly of uniform CH fragments in a one-pot multi-enzyme system. This strategy, which combined heteropolymer digestion, sugar nucleotide in situ generation, and sugar chain synchronized polymerization, provides a robust toolbox for structural-defined polysaccharides synthesis.
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http://dx.doi.org/10.1016/j.carres.2021.108442DOI Listing
September 2021

Dosimetric Comparison, Treatment Efficiency Estimation, and Biological Evaluation of Popular Stereotactic Radiosurgery Options in Treating Single Small Brain Metastasis.

Front Oncol 2021 5;11:716152. Epub 2021 Aug 5.

Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objectives: This study aimed to show the advantages of each stereotactic radiosurgery (SRS) treatment option for single small brain metastasis among Gamma Knife (GK), Cone-based VMAT (Cone-VMAT), and MLC-based CRT (MLC-CRT) plans.

Materials And Methods: GK, Cone-VMAT, and MLC-CRT SRS plans were retrospectively generated for 11 patients with single small brain metastasis whose volume of gross tumor volume (GTV) ranged from 0.18 to 0.76 cc (median volume 0.60 cc). Dosimetric parameters, treatment efficiency, and biological parameters of the three techniques were compared and evaluated. The metric variation with the planning target volume (PTV) was also studied.

Results: The conformity index (CI) was similar in GK and MLC-CRT plans, higher than Cone-VMAT. Cone-VMAT achieved comparable volume covered by 12 Gy (V12) and gradient index (GI) as GK, lower than MLC-CRT. The heterogeneity index (HI) of GK, Cone-VMAT, and MLC-CRT decreased sequentially. GK gave the lowest volume covered by 3 Gy (V3) and 6 Gy (V6), while MLC-CRT got the highest. The beam-on time and treatment time of GK, Cone-VMAT, and MLC-CRT decreased in turn. Tumor control probability (TCP) of all three SRS plans was greater than 98%, and normal tissue complication probability (NTCP) of all organs at risk (OARs) was below 0.01%. GK and Cone-VMAT resulted in superior TCP and NTCP of the normal brain tissue than MLC-CRT. The relative value of Cone-VMAT and GK for all metrics hardly changed with the target volume. Except for the unchanged HI and TCP, the other results of MLC-CRT with respect to GK improved as the target volume increased. MLC-CRT could produce higher CI than GK and Cone-VMAT when the target volume increased above 2 and 1.44 cc, respectively.

Conclusion: For single small brain metastases, Cone-VMAT may be used as an alternative to GK-free centers. In addition to the advantage of short treatment time, MLC-CRT showed superiority in CI as the target volume increased. Treatment centers can choose appropriate SRS technique on a case-by-case basis according to institutional conditions and patients' individual needs.
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http://dx.doi.org/10.3389/fonc.2021.716152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447903PMC
August 2021

Accurate diagnosis of lung tissues for 2D Raman spectrogram by deep learning based on short-time Fourier transform.

Anal Chim Acta 2021 Sep 2;1179:338821. Epub 2021 Jul 2.

State Key Laboratory of Tribology, Tsinghua University, Beijing 100084, China.

Multivariate statistical analysis methods have an important role in spectrochemical analyses to rapidly identify and diagnose cancer and the subtype. However, utilizing these methods to analyze lager amount spectral data is challenging, and poses a major bottleneck toward achieving high accuracy. Here, a new convolutional neural networks (CNN) method based on short-time Fourier transform (STFT) to diagnose lung tissues via Raman spectra readily is proposed. The models yield that the accuracies of the new method are higher than the conventional methods (principal components analysis -linear discriminant analysis and support vector machine) for validation group (95.2% vs 85.5%, 94.4%) and test group (96.5% vs 90.4%, 93.9%) after cross-validation. The results illustrate that the new method which converts one-dimensional Raman data into two-dimensional Raman spectrograms improve the discriminatory ability of lung tissues and can achieve automatically accurate diagnosis of lung tissues.
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http://dx.doi.org/10.1016/j.aca.2021.338821DOI Listing
September 2021

A peptide CORO1C-47aa encoded by the circular non-coding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis.

J Biol Chem 2021 Sep 14:101182. Epub 2021 Sep 14.

Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China. Electronic address:

Circular RNAs (circRNA) are a novel class of widespread non-coding RNAs (ncRNAs) that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames (sORFs) in ncRNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, are not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared to matched paracancerous tissue. The hsa-circ-0000437 contains a sORF encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain and blocking the association between ARNT and TACC3 which led to reduced expression of VEGF ultimately lead to reduced angiogenesis. The anti-tumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anti-carcinoma therapies and warrants further investigation.
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http://dx.doi.org/10.1016/j.jbc.2021.101182DOI Listing
September 2021

TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response.

Nucleic Acids Res 2021 Sep 17. Epub 2021 Sep 17.

Department of Data Science, Dana Farber Cancer Institute, Boston, MA 02215, USA.

Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of which 832 were from immune checkpoint blockade (ICB) studies. We manually annotated the sample metadata, such as cell line, mouse strain, transplantation site, treatment, and response status, and uniformly processed and quality-controlled the RNA-seq data. Besides data download, TISMO provides interactive web interfaces to investigate whether specific gene expression, pathway enrichment, or immune infiltration level is associated with differential immunotherapy response. TISMO is available at http://tismo.cistrome.org.
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http://dx.doi.org/10.1093/nar/gkab804DOI Listing
September 2021

Prevalence and trends in obesity among Austrian conscripts from 1983 to 2017.

Wien Klin Wochenschr 2021 Sep 17. Epub 2021 Sep 17.

Department of Epidemiology, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15, Vienna, Austria.

This article describes the recent prevalence and trend in weight status in young men over three and half decades among Austrian conscripts overall and by subgroups defined by education and smoking behavior. We extracted medical record data from six medical examination stations across the country of all Austrian military conscripts (aged 17-19 years) recruited between 1983 and 2017 (n = 1.5 million). Weight and height were measured to calculate body mass index (BMI). Mean BMI increased from 22.7 to 24.3 kg/m between 1983 and 2017. Over time, the prevalence of obesity (BMI ≥ 30 kg/m) increased from 1.6% (95% CI 1.6-1.7%) to 8.2% (95% CI 8.1-8.3%). The prevalence of obesity among Austrian young men increased remarkably in the past 35 years. Higher levels of education appeared to be associated with lower prevalence of obesity, particularly among the non-smokers.
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http://dx.doi.org/10.1007/s00508-021-01941-9DOI Listing
September 2021

Tai Chi for cancer survivors: A systematic review toward consensus-based guidelines.

Cancer Med 2021 Sep 17. Epub 2021 Sep 17.

Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, USA.

To manage acute, long-term, and late effects of cancer, current guidelines recommend moderate-to-vigorous intensity aerobic and resistance exercise. Unfortunately, not all cancer survivors are able or willing to perform higher intensity exercise during difficult cancer treatments or because of other existing health conditions. Tai Chi is an equipment-free, multicomponent mind-body exercise performed at light-to-moderate intensity that may provide a more feasible alternative to traditional exercise programs for some cancer survivors. This systematic review evaluated the therapeutic efficacy of Tai Chi across the cancer care continuum. We searched MEDLINE/PubMed, Embase, SCOPUS, and CINAHL databases for interventional studies from inception to 18 September 2020. Controlled trials of the effects of Tai Chi training on patient-reported and objectively measured outcomes in cancer survivors were included. Study quality was determined by the RoB 2 tool, and effect estimates were evaluated using the Best Evidence Synthesis approach. Twenty-six reports from 14 trials (one non-randomized controlled trial) conducted during (n = 5) and after treatment (after surgery: n = 2; after other treatments: n = 7) were included. Low-level evidence emerged to support the benefits of 40-60 min of thrice-weekly supervised Tai Chi for 8-12 weeks to improve fatigue and sleep quality in cancer survivors. These findings need to be confirmed in larger trials and tested for scaling-up potential. Insufficient evidence was available to evaluate the effects of Tai Chi on other cancer-related outcomes. Future research should examine whether Tai Chi training can improve a broader range of cancer outcomes including during the pre-treatment and end of life phases.
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http://dx.doi.org/10.1002/cam4.4273DOI Listing
September 2021

Nanocomplex made up of antimicrobial metallo-supramolecules and model biomembranes - characterization and enhanced fluorescence.

Nanoscale 2021 Sep 17;13(35):14973-14979. Epub 2021 Sep 17.

Polymer Program, Institute of Material Science, University of Connecticut, Storrs, Connecticut 06269, USA.

Antimicrobial pentatopic 2,2':6',2''-terpyridines that form 3-D supramolecular hexagonal prisms with Cd through coordination driven self-assembly can be entrapped by lipid discoidal bicelles, composed of 1,2-dipalmitoyl--3-phosphocholine, 1,2-dihexanoyl--3-phosphocholine and 1,2-dipalmitoyl--3-phospho-(1'-rac-glycerol) lipid, forming a well-defined nanocomplex. Structural characterization performed by very small angle neutron scattering, small angle X-ray scattering and transmission electron microscopy suggests that the hexagonal prisms are preferably located at the rim of bicellar discs with the hexagonal face in parallel with the bilayers, instead of face-to-face stacking. Such a configuration reduces the π-π interaction and consequently enhances the fluorescence emission. Since novel supramolecules were reported to have antibiotic functions, this study provides insight into the interactions of antimicrobial supermolecules with lipid membranes, leading to potential theranostic applications.
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http://dx.doi.org/10.1039/d1nr04083aDOI Listing
September 2021

Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role.

Front Genet 2021 31;12:714915. Epub 2021 Aug 31.

Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.

Background: Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 () single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between polymorphisms and GC.

Materials And Methods: A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of and GC risk by logistic regression in multiple genetic models. The prognostic value of in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of , various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations.

Results: Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1-1.63), < 0.01; HR (95% CI) = 1.4 (1.07-1.84), = 0.01]. Bioinformatic analysis revealed that was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC.

Conclusion: Patients with high expression of had a poor prognosis in GC, and SNPs in were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.
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http://dx.doi.org/10.3389/fgene.2021.714915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438327PMC
August 2021

Exploring the Symbiotic Mechanism of a Virus-Mediated Endophytic Fungus in Its Host by Dual Unique Molecular Identifier-RNA Sequencing.

mSystems 2021 Sep 14:e0081421. Epub 2021 Sep 14.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural Universitygrid.35155.37, Hubei Province, Wuhan, China.

The symbiosis of endophytes and plants is universal in nature. However, how endophytes grow in plants is not entirely clear. Previously, we reported that a virus-infected fungal pathogen could grow in plants as an endophyte. In this study, we utilized Sclerotinia sclerotiorum strain DT-8, a virus-mediated endophyte, to investigate the mechanism of symbiosis with rapeseed by dual unique molecular identifier-RNA sequencing (dual-UMI RNA-seq). We found that the expressions of genes encoding amylase/glucoamylase, glucose transporters, and rapeseed ugars ill ventually be xported ransporter 11 (SWEET11) were upregulated. It suggested that strain DT-8 might utilize plant starch as a nutrient. The defense systems of rapeseed were also activated, such as production of reactive oxygen species, phenylpropanoids, and brassinin, to control the growth of strain DT-8, while strain DT-8 counteracted host suppression by producing effector-like proteins, detoxification enzymes, and antioxidant components. Moreover, rapeseed also upregulated pectate lyase and pectinesterase genes to facilitate the colonization by strain DT-8. Our findings provide novel insights into the interaction of virus-mediated endophytes and their hosts that warrant further study. Although endophytes are widespread in nature, the interactions between endophytes and their hosts are still not fully understood. Members of a unique class of endophytes, the virus-mediated endophytic fungi, are continuously being discovered and have received wide attention. In this study, we investigated the interaction between a mycovirus-mediated endophytic fungus and its host rapeseed by using dual-UMI RNA-seq. According to the dual-UMI RNA-seq results, an aerial view of symbiotic mechanism under balanced regulation was suggested. This research expands our understanding of the symbiotic mechanisms of virus-fungus-plant interactions and could establish a foundation for the further development of practical application with virus-mediated hypovirulent fungi.
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http://dx.doi.org/10.1128/mSystems.00814-21DOI Listing
September 2021

Prevention and control strategies for the post-pandemic era: finding a balance between COVID-19 and reviving medical service.

J Infect Dev Ctries 2021 08 31;15(8):1074-1079. Epub 2021 Aug 31.

Department of Hospital-Acquired Infection Control, Beijing Jishuitan Hospital, Beijing, China.

Introduction: Public life in China is gradually returning to normal with strong measures in coronavirus 2019 (COVID-19) control. Because of the long-term effects of COVID-19, medical institutions had to make timely adjustments to control policies and priorities to balance between COVID-19 prevention and daily medical services.

Methodology: The framework for infection prevention and control in the inpatient department was effectively organized at both hospital and department levels. A series of prevention and control strategies was implemented under this leadership: application of rigorous risk assessment and triage before admission through a query list; classifying patients into three risk levels and providing corresponding medical treatment and emergency handling; establishing new ward visiting criteria for visitors; designing procedures for PPE and stockpile management; executing specialized disinfection and medical waste policies.

Results: Till June 2020, the bed occupancy had recovered from 20.0% to 88.1%. In total, 13045 patients were received in our hospital, of which 54 and 127 patients were identified as high-risk and medium-risk, respectively, and 2 patients in the high-risk group were eventually laboratory-confirmed with COVID-19. No hospital-acquired infection of COVID-19 has been observed since the emergency appeared.

Conclusions: The strategies ensured early detection and targeted prevention of COVID-19 following the COVID-19 pandemic, which improved the recovery of medical services after the pandemic.
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http://dx.doi.org/10.3855/jidc.13634DOI Listing
August 2021

Graphene-Based Materials for Flexible Lithium-Sulfur Batteries.

ACS Nano 2021 Sep 13. Epub 2021 Sep 13.

Shenzhen Geim Graphene Center, Tsinghua-Berkeley Shenzhen Institute & Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, People's Republic of China.

The increasing demand for wearable electronic devices necessitates flexible batteries with high stability and desirable energy density. Flexible lithium-sulfur batteries (FLSBs) have been increasingly studied due to their high theoretical energy density through the multielectron chemistry of low-cost sulfur. However, the implementation of FLSBs is challenged by several obstacles, including their low practical energy density, short life, and poor flexibility. Various graphene-based materials have been applied to address these issues. Graphene, with good conductivity and flexibility, exhibits synergistic effects with other active/catalytic/flexible materials to form multifunctional graphene-based materials, which play a pivotal role in FLSBs. This review summarizes the recent progress of graphene-based materials that have been used as various FLSB components, including cathodes, interlayers, and anodes. Particular attention is focused on the precise nanostructures, graphene efficacy, interfacial effects, and battery layout for realizing FLSBs with good flexibility, energy density, and cycling stability.
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http://dx.doi.org/10.1021/acsnano.1c03183DOI Listing
September 2021

Entropy-Enthalpy Compensations Fold Proteins in Precise Ways.

Int J Mol Sci 2021 Sep 6;22(17). Epub 2021 Sep 6.

National Key Laboratory of Science and Technology on Advanced Composites in Special Environments, Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin 150080, China.

Exploring the protein-folding problem has been a longstanding challenge in molecular biology and biophysics. Intramolecular hydrogen (H)-bonds play an extremely important role in stabilizing protein structures. To form these intramolecular H-bonds, nascent unfolded polypeptide chains need to escape from hydrogen bonding with surrounding polar water molecules under the solution conditions that require entropy-enthalpy compensations, according to the Gibbs free energy equation and the change in enthalpy. Here, by analyzing the spatial layout of the side-chains of amino acid residues in experimentally determined protein structures, we reveal a protein-folding mechanism based on the entropy-enthalpy compensations that initially driven by laterally hydrophobic collapse among the side-chains of adjacent residues in the sequences of unfolded protein chains. This hydrophobic collapse promotes the formation of the H-bonds within the polypeptide backbone structures through the entropy-enthalpy compensation mechanism, enabling secondary structures and tertiary structures to fold reproducibly following explicit physical folding codes and forces. The temperature dependence of protein folding is thus attributed to the environment dependence of the conformational Gibbs free energy equation. The folding codes and forces in the amino acid sequence that dictate the formation of β-strands and α-helices can be deciphered with great accuracy through evaluation of the hydrophobic interactions among neighboring side-chains of an unfolded polypeptide from a β-strand-like thermodynamic metastable state. The folding of protein quaternary structures is found to be guided by the entropy-enthalpy compensations in between the docking sites of protein subunits according to the Gibbs free energy equation that is verified by bioinformatics analyses of a dozen structures of dimers. Protein folding is therefore guided by multistage entropy-enthalpy compensations of the system of polypeptide chains and water molecules under the solution conditions.
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http://dx.doi.org/10.3390/ijms22179653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431812PMC
September 2021

Imparting α-Borophene with High Work Function by Fluorine Adsorption: A First-Principles Investigation.

Langmuir 2021 Sep 9;37(37):11027-11040. Epub 2021 Sep 9.

Key Laboratory of Functional Inorganic Material Chemistry (Ministry of Education) and School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China.

Increasing the work function of borophene over a large range is crucial for the development of borophene-based anode materials for highly efficient electronic devices. In this study, the effect of fluorine adsorption on the structures and stabilities, particularly on the work function, of α-borophene (BBP), was systematically investigated via first-principles density functional theory. The calculations indicated that BBP was well-stabilized by fluorine adsorption and the work functions of metallic fluorine-adsorbed BBPs (F-BBPs) sharply increased with increasing fluorine content. Moreover, the work function of F-BBP was close to that of the frequently used anode material Au and even, for other F-BBPs, higher than that of Pt. Furthermore, we have comprehensively discussed the factors, including substrate deformation, charge transfer, induced dipole moment, and Fermi and vacuum energy levels, affecting the improvement of work function. Particularly, we have demonstrated that the charge redistribution of the substrate induced by the bonding interaction between fluorine and the matrix predominantly contributes to the observed increase in the work function. Additionally, the effect of fluorine adsorption on the increase in the work function of BBP was significantly stronger than that of silicene or graphene. Our results concretely support the fact that F-BBPs can be extremely attractive anode materials for electronic device applications.
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http://dx.doi.org/10.1021/acs.langmuir.1c01598DOI Listing
September 2021

Oxidized low-density lipoprotein links hypercholesterolemia and bladder cancer aggressiveness by promoting cancer stemness.

Cancer Res 2021 Sep 3. Epub 2021 Sep 3.

Department of Laboratory Animal Science, Fudan University

Hypercholesterolemia is a prevalent metabolic disorder that has been implicated in the development of steroid-targeted cancers. However, the link between hypercholesterolemia and urinary bladder cancer (UBC), a non-steroid-targeted cancer, remains unresolved. Here we show that diet- and Ldlr deficiency-induced hypercholesterolemia enhances both UBC stemness and progression. Inhibition of intestinal cholesterol absorption by Ezetimibe reversed diet-induced hypercholesterolemia and cancer stemness. As a key component in hypercholesterolemic sera, oxidized low-density lipoprotein (ox-LDL), but not native low-density lipoprotein-cholesterol or metabolite 27-hydroxycholesterol, increased cancer stemness through its receptor CD36. Depletion of CD36, ectopic expression of an ox-LDL binding-disabled mutant form of CD36(K164A), and the neutralization of ox-LDL and CD36 via neutralizing antibodies all reversed ox-LDL-induced cancer stemness. Mechanistically, ox-LDL enhanced the interaction of CD36 and JAK2, inducing phosphorylation of JAK2 and subsequently activating STAT3 signaling, which was not mediated by JAK1 or Src in UBC cells. Finally, ox-LDL levels in serum predicted poor prognosis, and the ox-LDLhigh signature predicted worse survival in UBC patients. These findings indicate that ox-LDL links hypercholesterolemia with UBC progression by enhancing cancer stemness. Lowering serum ox-LDL or targeting the CD36/JAK2/STAT3 axis might serve as a potential therapeutic strategy for UBCs with hypercholesterolemia. Moreover, elevated ox-LDL may serve as a biomarker for UBC.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0646DOI Listing
September 2021

Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers.

J Immunother Cancer 2021 Sep;9(9)

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China

Background: Defects in replication repair-associated DNA polymerases often manifest an ultra-high tumor mutational burden (TMB), which is associated with higher probabilities of response to immunotherapies. The functional and clinical implications of different polymerase variants remain unclear.

Methods: Targeted next-generation sequencing using a 425-cancer gene panel, which covers all exonic regions of three polymerase genes (, , and ), was conducted in a cohort of 12,266 patients across 16 different tumor types from January 2017 to January 2019. Prognostication of variant-positive patients was performed using a cohort of 4679 patients from the The Cancer Genome Atlas (TCGA) datasets.

Results: The overall prevalence of somatic and germline polymerase variants was 4.2% (95% CI 3.8% to 4.5%) and 0.7% (95% CI 0.5% to 0.8%), respectively, with highest frequencies in endometrial, urinary, prostate, and colorectal cancers (CRCs). While most germline polymerase variants showed no clear functional consequences, we identified a candidate p.T466A affecting the exonuclease domain of POLE, which might be underlying the early onset in a case with childhood CRC. Low frequencies of known hot-spot somatic mutations in were detected and were associated with younger age, the male sex, and microsatellite stability. In both the panel and TCGA cohorts, drivers exhibited high frequencies of alterations in genes in the DNA damage and repair (DDR) pathways, including , , , and . Variants of unknown significance (VUS) of different polymerase domains showed variable penetrance with those in the exonuclease domain of and displaying high TMB. VUS in genes exhibited an additive effect as carriers of multiple VUS had exponentially increased TMB and prolonged overall survival. Similar to cases with driver mutations, the TMB-high VUS samples showed DDR pathway involvement and polymerase hypermutation signatures. Combinatorial analysis of and DDR pathway status further supported the potential additive effects of VUS and DDR pathway genes and revealed distinct prognostic subclasses that were independent of cancer type and TMB.

Conclusions: Our results demonstrate the pathogenicity and additive prognostic value of VUS and DDR pathway gene alterations and suggest that genetic testing may be warranted in patients with diverse solid tumors.
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http://dx.doi.org/10.1136/jitc-2021-002336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420654PMC
September 2021

The antioxidant N-acetylcysteine promotes immune response and inhibits epithelial-mesenchymal transition to alleviate pulmonary fibrosis in chronic obstructive pulmonary disease by suppressing the VWF/p38 MAPK axis.

Mol Med 2021 09 3;27(1):97. Epub 2021 Sep 3.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, 330000, Jiangxi, People's Republic of China.

Background/aim: N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD). COPD is often characterized by fibrosis of the small airways. This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD.

Methods: A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established. Cigarette smoke extract (CSE) cell models were constructed. The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3, CD4, CD8 and CD4/CD8T lymphocytes.

Results: Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD. NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression. NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3, CD4, CD8 and CD4/CD8T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats. NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis.

Conclusions: Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.
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http://dx.doi.org/10.1186/s10020-021-00342-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414683PMC
September 2021

Robotic sample changers for macromolecular X-ray crystallography and biological small-angle X-ray scattering at the National Synchrotron Light Source II.

J Synchrotron Radiat 2021 Sep 23;28(Pt 5):1649-1661. Epub 2021 Aug 23.

National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY 11973, USA.

Here we present two robotic sample changers integrated into the experimental stations for the macromolecular crystallography (MX) beamlines AMX and FMX, and the biological small-angle scattering (bioSAXS) beamline LiX. They enable fully automated unattended data collection and remote access to the beamlines. The system designs incorporate high-throughput, versatility, high-capacity, resource sharing and robustness. All systems are centered around a six-axis industrial robotic arm coupled with a force torque sensor and in-house end effectors (grippers). They have the same software architecture and the facility standard EPICS-based BEAST alarm system. The MX system is compatible with SPINE bases and Unipucks. It comprises a liquid nitrogen dewar holding 384 samples (24 Unipucks) and a stay-cold gripper, and utilizes machine vision software to track the sample during operations and to calculate the final mount position on the goniometer. The bioSAXS system has an in-house engineered sample storage unit that can hold up to 360 samples (20 sample holders) which keeps samples at a user-set temperature (277 K to 300 K). The MX systems were deployed in early 2017 and the bioSAXS system in early 2019.
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http://dx.doi.org/10.1107/S1600577521007578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415329PMC
September 2021

Naked cuticle inhibits wingless signaling in Drosophila wing development.

Biochem Biophys Res Commun 2021 Oct 28;576:1-6. Epub 2021 Aug 28.

School of Life Science and Technology, MOE Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing, 210096, China. Electronic address:

Wnt signaling is one of the major signaling pathways that regulate cell differentiation, tissue patterning and stem cell homeostasis and its dysfunction causes many human diseases, such as cancer. It is of tremendous interests to understand how Wnt signaling is regulated in a precise manner both temporally and spatially. Naked cuticle (Nkd) acts as a negative-feedback inhibitor for Wingless (Wg, a fly Wnt) signaling in Drosophila embryonic development. However, the role of Nkd remains controversial in later fly development, particularly on the canonical Wg pathway. In the present study, we show that nkd is essential for wing pattern formation, such that both gain and loss of nkd result in the disruption of Wg target expression in larvae stage and abnormal adult wing morphologies. Furthermore, we demonstrate that a thirty amino acid fragment in Nkd, identified previously in Wharton lab, is critical for the canonical Wg signaling, but is dispensable for Wg/planar cell polarity pathway. Putting aside the pleiotropic nature of nkd function, i.e. its role in the Decapentaplegic signaling, we conclude that Nkd universally inhibits the canonical Wg pathway across a life span of Drosophila development.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.077DOI Listing
October 2021

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

Signal Transduct Target Ther 2021 Sep 1;6(1):329. Epub 2021 Sep 1.

Department of Cardiology, Affiliated Hospital of Shanxi University of Chinese Medicine, Xianyang, Shanxi, China.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Z value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).
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http://dx.doi.org/10.1038/s41392-021-00741-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410855PMC
September 2021

[Retracted] Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma and .

Mol Med Rep 2021 Nov 1;24(5). Epub 2021 Sep 1.

Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Following the publication of this paper, the authors contacted the Editorial Office to request that the article be retracted on account of an inability to obtain consistent results after having repeated the experiments portrayed in Figs. 1B and 3B. Independently, it was drawn to the Editor's attention that certain of the western blotting data shown in these figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these other articles were under consideration for publication at the same time as the above article was submitted for publication to Molecular Medicine Reports, the Editor has agreed to the authors' request that this article should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in 12: 753‑759, 2015; DOI: 10.3892/mmr.2015.3425].
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http://dx.doi.org/10.3892/mmr.2021.12391DOI Listing
November 2021

Organic Dye/CsAgBiBr Double Perovskite Heterojunction Solar Cells.

J Am Chem Soc 2021 Sep 1;143(36):14877-14883. Epub 2021 Sep 1.

Key Laboratory of Physics and Technology for Advanced Batteries (Ministry of Education), College of Physics, Jilin University, Changchun 130012, China.

The photovoltaic performance of CsAgBiBr perovskite is limited by its light-harvesting ability owing to its broad bandgap. Here, we introduced three indoline dyes, D102, D131, and D149, to sensitize the TiO electron transport layer that was employed in the CsAgBiBr perovskite solar cells (PSCs). The perovskite-indoline dye hybrid cells worked with higher power conversion efficiencies (PCEs) than the corresponding dye-sensitized solar cells and the PSC. Extended absorption resulted in a higher short-circuit current density, up to 8.24 mA cm, and a maximum PCE of 4.23% in the case of D149, for instance. The double perovskite worked as a p-type interlayer between the dyes and spiro-OMeTAD to convey the holes from the former to the latter, resulting in enhancement in the overall performance.
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http://dx.doi.org/10.1021/jacs.1c07200DOI Listing
September 2021

The Relationship Between Circulating Bone Morphogenetic Protein-4 and Inflammation Cytokines in Patients Undergoing Thoracic Surgery: A Prospective Randomized Study.

J Inflamm Res 2021 21;14:4069-4077. Epub 2021 Aug 21.

Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.

Background: Bone morphogenetic protein-4 (BMP4) has been identified as an inflammation regulator in the diseases of arteries and other organs. However, the relationship between circulating BMP4 and perioperative inflammation remains unclear.

Patients And Methods: Forty patients undergoing lobectomy were randomly allocated into the Control group (not receiving flurbiprofen) and the Flurb group (received 100mg flurbiprofen during surgery). Arterial blood was obtained before surgery (T1), at the end of surgery (T2), and 24 hours after surgery (T3) to test the plasma concentrations of BMP4, its antagonist Noggin, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-10. The relationship between BMP4 and other variables and the effects of flurbiprofen on BMP4 changes were investigated.

Results: A total of 35 patients were included. Circulating BMP4 was positively correlated with IL-1β (<0.01, r=0.575) and TNF-α (<0.01, r=0.491), negatively correlated with IL-10 (<0.01, r=-0.675), but not correlated with Noggin. The plasma concentrations of BMP4, IL-1β, and TNF-α increased at T2 (<0.01, compared with T1) and decreased at T3 (<0.05, compared with T2). BMP4 concentrations at T3 were significantly higher than at T1 in the Control group (<0.05), while showing no significant difference in the Flurb group. However, in the Flurb group, the relative changes of BMP4 and IL-1β at T2 and T3 were significantly lower than those in the Control group.

Conclusion: Circulating BMP4 was elevated during surgery and highly correlated with inflammation cytokines. The elevation of BMP4 and inflammatory cytokines could be alleviated by flurbiprofen, indicating that BMP4 may exert pro-inflammatory properties via cyclooxygenase-II signaling pathways.
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http://dx.doi.org/10.2147/JIR.S324775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387642PMC
August 2021

Bioinspired Design of Sericin/Chitosan/[email protected]/GO Hydrogels for Efficiently Combating Resistant Bacteria, Rapid Hemostasis, and Wound Healing.

Polymers (Basel) 2021 Aug 21;13(16). Epub 2021 Aug 21.

National Marine Data and Information Service, Tianjin 300171, China.

Due to the spread of drug-resistant bacteria in hospitals, the development of antibacterial dressings has become a strategy to control wound infections caused by bacteria. Here, we reported a green strategy for in situ biomimetic syntheses of silver [email protected] frameworks/graphene oxide ([email protected]) in sericin/chitosan/polyvinyl alcohol hydrogel. [email protected] was synthesized in situ from the redox properties of tyrosine residues in silk sericin without additional chemicals, similar to a biomineralization process. The sericin/chitosan/[email protected] dressing possessed a high porosity, good water retention, and a swelling ratio. The hemolysis rate of the composite was 3.9% and the cell viability rate was 131.2%, which indicated the hydrogel possessed good biocompatibility. The composite also showed excellent lasting antibacterial properties against drug-sensitive and drug-resistant pathogenic bacteria. The composite possessed excellent hemostatic activity. The coagulation effect of the composite may be related to its effect on the red blood cells and platelets, but it has nothing to do with the activation of coagulation factors. An in vitro cell migration assay confirmed and an in vivo evaluation of mice indicated that the composite could accelerate wound healing and re-epithelialization. In summary, the composite material is an ideal dressing for accelerating hemostasis, preventing bacterial infection, and promoting wound healing.
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http://dx.doi.org/10.3390/polym13162812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398496PMC
August 2021

The making of an ovarian niche.

Science 2021 07;373(6552):282-283

Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.

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http://dx.doi.org/10.1126/science.abj8347DOI Listing
July 2021

Complete mitochondrial genome of the planthopper (Germar, 1830) (Hemiptera: Fulgoromorpha: Dictyopharidae).

Mitochondrial DNA B Resour 2021 16;6(9):2667-2668. Epub 2021 Aug 16.

School of Geography and Resources, Guizhou Education University, Guiyang, PR China.

The first complete mitochondrial genome of a dictyopharid planthopper, (Germar, 1830) (Hemiptera: Fulgoroidea: Dictyopharidae) is sequenced. The 15,349 bp long complete mitogenome contains 13 protein-coding genes (PCGs), 22 genes, two rRNA genes, and 1 A + T-rich region with an arrangement identical to that observed in most insect mitogenomes (GenBankNo. MW441850). All PCGs start with ATN, and end with TAN or single T (, , and ). A phylogenetic analysis places as sister to Fulgoridae confirming a sister relationship between Dictyopharidae and Fulgoridae.
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http://dx.doi.org/10.1080/23802359.2021.1964400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381974PMC
August 2021

Geographic and Socioeconomic Disparities in Major Lower Extremity Amputation Rates in Metropolitan Areas.

J Am Heart Assoc 2021 Sep 25;10(17):e021456. Epub 2021 Aug 25.

Penn Cardiovascular Outcomes, Quality and Evaluative Research Center University of Pennsylvania Philadelphia PA.

Background Rates of major lower extremity amputation in patients with peripheral artery disease are higher in rural communities with markers of low socioeconomic status, but most Americans live in metropolitan areas. Whether amputation rates vary within US metropolitan areas is unclear, as are characteristics of high amputation rate urban communities. Methods and Results We estimated rates of major lower extremity amputation per 100 000 Medicare beneficiaries between 2010 and 2018 at the ZIP code level among ZIP codes with ≥100 beneficiaries. We described demographic characteristics of high and low amputation ZIP codes, and the association between major amputation rate and 3 ZIP code-level markers of socioeconomic status-the proportion of patients with dual eligibility for Medicaid, median household income, and Distressed Communities Index score-for metropolitan, micropolitan, and rural ZIP code cohorts. Between 2010 and 2018, 188 995 Medicare fee-for-service patients living in 31 391 ZIP codes with ≥100 beneficiaries had a major lower extremity amputation. The median (interquartile range) ZIP code-level number of amputations per 100 000 beneficiaries was 262 (75-469). Though nonmetropolitan ZIP codes had higher rates of major amputation than metropolitan areas, 78.2% of patients undergoing major amputation lived in metropolitan areas. Compared with ZIP codes with lower amputation rates, top quartile amputation rate ZIP codes had a greater proportion of Black residents (4.4% versus 17.5%, <0.001). In metropolitan areas, after adjusting for clinical comorbidities and demographics, every $10 000 lower median household income was associated with a 4.4% (95% CI, 3.9-4.8) higher amputation rate, and a 10-point higher Distressed Communities Index score was associated with a 3.8% (95% CI, 3.4%-4.2%) higher amputation rate; there was no association between the proportion of patients eligible for Medicaid and amputation rate. These findings were comparable to the associations identified across all ZIP codes. Conclusions In metropolitan areas, where most individuals undergoing lower extremity amputation live, markers of lower socioeconomic status and Black race were associated with higher rates of major lower extremity amputation. Development of community-based tools for peripheral artery disease diagnosis and management targeted to communities with high amputation rates in urban areas may help reduce inequities in peripheral artery disease outcomes.
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http://dx.doi.org/10.1161/JAHA.121.021456DOI Listing
September 2021

gene genotype-phenotype correlation in neonates with Zellweger syndrome.

Transl Pediatr 2021 Jul;10(7):1825-1833

Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.

Background: Zellweger syndrome (ZS) is commonly manifested as facial deformities, hypotonia, and liver dysfunction. However, ZS caused by gene mutation shows a broad and dispersed clinical pattern. In this study, the gene in ZS was analyzed to enrich its clinical characteristics. Meanwhile, phenotypic and genotypic characteristics of Zellweger spectrum disorder (ZSD) induced by mutation were evaluated.

Methods: The clinical data of newborn with ZS in our hospital were analyzed retrospectively. We performed WES and found that the infant carried the gene variant. We searched the biomedical literature databases (PubMed, Web of Science, and EMBASE) to compare clinical features and genotypes.

Results: The neonate developed facial deformities, hypotonia, feeding difficulties, and seizures. Her homozygous variant was found in the gene (NM_017929: exon2: c.34del) inherited from both parents. Electronic databases, including our case, reported 32 pathogenic variants in . We found that variation c.292C> T accounted for the largest proportion of mutations (16/66, 24.24%). The proportion of deleterious mutations in ZS patients was significantly higher than that in NALD and IRD patients.

Conclusions: We identified pathogenic variations in the gene and expanded the known mutant spectrum. By comparing patients with mutations, the study determined that a significantly higher percentage of deleterious mutations in ZS was associated with severe clinical phenotypic characteristics.
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http://dx.doi.org/10.21037/tp-21-103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349955PMC
July 2021
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