Publications by authors named "Xiang Zhang"

2,277 Publications

  • Page 1 of 1

3D-printed silica with nanoscale resolution.

Nat Mater 2021 Oct 14. Epub 2021 Oct 14.

Department of Materials Science and NanoEngineering, Rice University, Houston, TX, USA.

Fabricating inorganic materials with designed three-dimensional nanostructures is an exciting yet challenging area of research and industrial application. Here, we develop an approach to 3D print high-quality nanostructures of silica with sub-200 nm resolution and with the flexible capability of rare-earth element doping. The printed SiO can be either amorphous glass or polycrystalline cristobalite controlled by the sintering process. The 3D-printed nanostructures demonstrate attractive optical properties. For instance, the fabricated micro-toroid optical resonators can reach quality factors (Q) of over 10. Moreover, and importantly for optical applications, doping and codoping of rare-earth salts such as Er, Tm, Yb, Eu and Nd can be directly implemented in the printed SiO structures, showing strong photoluminescence at the desired wavelengths. This technique shows the potential for building integrated microphotonics with silica via 3D printing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41563-021-01111-2DOI Listing
October 2021

Th17/Treg imbalance in peripheral blood from patients with intracranial aneurysm.

J Neurosurg Sci 2021 Oct 14. Epub 2021 Oct 14.

Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Background: Spontaneous subarachnoid hemorrhage (SAH) is highly associated with ruptured intracranial aneurysm (IA), which dramatically increases neurological disabilities or mortality in patients. The balance between T helper cells (Th17) and regulatory T cells (Treg) plays a crucial role in regulating immune-inflammatory response. In the current study, we aim to obtain a better understanding of the role of Th17 and Treg cells in patients with IA.

Methods: 138 patients total participated in this study, including ruptured aneurysms group (Ruptured IA, RIA, n=70 cases) and unruptured aneurysms group (Unruptured IA, URIA, n=68 cases). Additionally, 76 cases of healthy subjects were selected as control group. The frequencies of Th17 and Treg cells were determined using flow cytometry. The serum levels of cytokines including IL-17, IL-23, IL-10, and TGF-β1 were determined using ELISA. mRNA was isolated from the whole blood. FOXP3 and RCRc mRNA expressions were detected using RT-qPCR.

Results: The percentage of Th17 cells in peripheral blood from RIA patients was higher than URIA patients (P<0.01), whereas the percentage of Treg cells in peripheral blood from RIA was significantly lower when compared with URIA patients (P<0.001). The serum levels of IL-17 (P<0.01) and IL-23 (P<0.05) were markedly increased while the levels of IL-10 (P<0.01) and TGF-β1 (P<0.05) were decreased in RIA patients when compared with URIA patients. Lastly, the mRNA level of RCRc was significantly increased in RIA vs. URIA patients (P<0.001). By contrast, FOXP3 mRNA level was significantly decreased in RIA vs. URIA patients (P<0.001).

Conclusions: In the current study, we demonstrated the imbalance of Th17/Treg in patients with IA, and the frequencies of Th17 cells were positively correlated with the severity of IA-induced SAH. These results provided data to support that targeting Th17/Treg could act as an effective approach for the management of IA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0390-5616.21.05567-3DOI Listing
October 2021

Manipulation on active electronic states of metastable phase β-NiMoO for large current density hydrogen evolution.

Nat Commun 2021 Oct 13;12(1):5960. Epub 2021 Oct 13.

Institute of Special Materials and Technology, Fudan University, Shanghai, China.

Non-noble transition metal oxides are abundant in nature. However, they are widely regarded as catalytically inert for hydrogen evolution reaction (HER) due to their scarce active electronic states near the Fermi-level. How to largely improve the HER activity of these kinds of materials remains a great challenge. Herein, as a proof-of-concept, we design a non-solvent strategy to achieve phosphate substitution and the subsequent crystal phase stabilization of metastable β-NiMoO. Phosphate substitution is proved to be imperative for the stabilization and activation of β-NiMoO, which can efficiently generate the active electronic states and promote the intrinsic HER activity. As a result, phosphate substituted β-NiMoO exhibits the optimal hydrogen adsorption free energy (-0.046 eV) and ultralow overpotential of -23 mV at 10 mA cm in 1 M KOH for HER. Especially, it maintains long-term stability for 200 h at the large current density of 1000 mA cm with an overpotential of only -210 mV. This work provides a route for activating transition metal oxides for HER by stabilizing the metastable phase with abundant active electronic states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-26256-1DOI Listing
October 2021

A Novel Immunomodulatory 27-Gene Signature to Predict Response to Neoadjuvant Immunochemotherapy for Primary Triple-Negative Breast Cancer.

Cancers (Basel) 2021 Sep 28;13(19). Epub 2021 Sep 28.

Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

A precise predictive biomarker for TNBC response to immunochemotherapy is urgently needed. We previously established a 27-gene IO signature for TNBC derived from a previously established 101-gene model for classifying TNBC. Here we report a pilot study to assess the performance of a 27-gene IO signature in predicting the pCR of TNBC to preoperative immunochemotherapy. We obtained RNA sequencing data from the primary tumors of 55 patients with TNBC, who received neoadjuvant immunochemotherapy with the PD-L1 blocker durvalumab. We determined the power and accuracy in predicting pCR for the immunomodulatory (IM) subtype identified by the 101-gene model, the 27-gene IO signature, and PD-L1 expression by immunohistochemistry (IHC). The pCR rate was 45% (25/55). The odds ratios for pCR were as follows: IM subtype by 101-gene model, 3.14 ( = 0.054); 27-gene IO signature, 4.13 ( = 0.012); PD-L1 expression by IHC, 2.63 ( = 0.106); 27-gene IO signature in combination with PD-L1 expression by IHC, 6.53 ( = 0.003). The 27-gene IO signature has the potential to predict the pCR of primary TNBC to neoadjuvant immunochemotherapy. Further analysis in a large cohort is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13194839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508147PMC
September 2021

Stress adaptation and virulence in Vibrio alginolyticus is mediated by two (p)ppGpp synthetase genes, relA and spoT.

Microbiol Res 2021 Sep 27;253:126883. Epub 2021 Sep 27.

State Key Laboratory of Marine Resource Utilization in the South China Sea, Hainan University, Haikou, 570228, Hainan Province, PR China; Laboratory of Development and Utilization of Marine Microbial Resource, Hainan University, Haikou, 570228, Hainan Province, PR China; Key Laboratory of Tropical Hydrobiology and Biotechnology of Hainan Province, Haikou, Hainan, 570228, PR China; College of Marine Sciences, Hainan University, Haikou, 570228, Hainan Province, PR China. Electronic address:

Vibrio alginolyticus belongs to gram-negative opportunistic pathogen realm infecting humans and aquatic animals causing severe economic losses. The (p)ppGpp-mediated stringent response is corroborated to stress adaptation and virulence of pathogenic mechanisms. Limited reports are documented for the intricate assessment of (p)ppGpp synthetase genes in combating various stress adaptation and elucidation of virulence in V. alginolyticus remains unraveled. The present assessment comprises of generation of deletion mutants in the (p)ppGpp-deficient strains, ΔrelA (relA gene single mutant) and ΔrelAΔspoT (relA and spoT genes double mutant), and the complemented strains, ΔrelA+ and ΔrelAΔspoT+, were constructed to investigate the pivotal roles of (p)ppGpp synthetase genes in V. alginolyticus, respectively. Amino acid sequence alignment analysis initially revealed that RelA and SpoT possess relatively conserved domains and synthetase activity. Hydrolase activity was emancipated by SpoT alone showing variant mode of action. Compared with the wild type and complemented strains, the relA-deficient strain was more sensitive to amino acid starvation and mupirocin. Interestingly, the deletion of spoT resulted in a significant growth deficiency supplemented with bile salts, 3 % ethanol and heat shock. Rapid growth was observed in the stationary phase upon exposure to cold stress and lower doses of ethanol. Subsequently, disruption of (p)ppGpp synthetase genes caused the decline in swimming motility, enhanced biofilm formation, cell aggregation of V. alginolyticus, and reduced mortality of Litopenaeus vannamei. The expression levels of some virulence-associated genes were quantified affirming consistency established by pleiotropic phenotypes. The results are evident for putative roles of (p)ppGpp synthetase genes attributing essential roles for environmental adaption and virulence regulation in V. alginolyticus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micres.2021.126883DOI Listing
September 2021

Evolving cancer-niche interactions and therapeutic targets during bone metastasis.

Nat Rev Cancer 2021 Oct 5. Epub 2021 Oct 5.

Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.

Many cancer types metastasize to bone. This propensity may be a product of genetic traits of the primary tumour in some cancers. Upon arrival, cancer cells establish interactions with various bone-resident cells during the process of colonization. These interactions, to a large degree, dictate cancer cell fates at multiple steps of the metastatic cascade, from single cells to overt metastases. The bone microenvironment may even influence cancer cells to subsequently spread to multiple other organs. Therefore, it is imperative to spatiotemporally delineate the evolving cancer-bone crosstalk during bone colonization. In this Review, we provide a summary of the bone microenvironment and its impact on bone metastasis. On the basis of the microscopic anatomy, we tentatively define a roadmap of the journey of cancer cells through bone relative to various microenvironment components, including the potential of bone to function as a launch pad for secondary metastasis. Finally, we examine common and distinct features of bone metastasis from various cancer types. Our goal is to stimulate future studies leading to the development of a broader scope of potent therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41568-021-00406-5DOI Listing
October 2021

Polyethylene glycol diacrylate scaffold filled with cell-laden methacrylamide gelatin/alginate hydrogels used for cartilage repair.

J Biomater Appl 2021 Oct 4:8853282211044853. Epub 2021 Oct 4.

12636School of Mechanics & Safety Engineering, Zhengzhou University, Zhengzhou, China.

Natural cartilage tissue has excellent mechanical properties and has certain cellular components. At this stage, it is a great challenge to produce cartilage scaffolds with excellent mechanical properties, biocompatibility, and biodegradability. Hydrogels are commonly used in tissue engineering because of their excellent biocompatibility; however, the mechanical properties of commonly used hydrogels are difficult to meet the requirements of making cartilage scaffolds. The mechanical properties of high concentration polyethylene glycol diacrylate (PEGDA) hydrogel are similar to those of natural cartilage, but its biocompatibility is poor. Low concentration hydrogel has better biocompatibility, but its mechanical properties are poor. In this study, two different hydrogels were combined to produce cartilage scaffolds with good mechanical properties and strong biocompatibility. First, the PEGDA grid scaffold was printed with light curing 3D printing technology, and then the low concentration GelMA/Alginate hydrogel with chondral cells was filled into the PEGDA grid scaffold. After a series of cell experiments, the filling hydrogel with the best biocompatibility was screened out, and finally the filled hydrogel with cells and excellent biocompatibility was obtained. Cartilage tissue engineering scaffolds with certain mechanical properties were found to have a tendency of cartilage formation in in vitro culture. Compared with the scaffold obtained by using a single hydrogel, this molding method can produce a tissue engineering scaffold with excellent mechanical properties on the premise of ensuring biocompatibility, which has a certain potential application value in the field of cartilage tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08853282211044853DOI Listing
October 2021

PLK1-dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV-infected mice.

EMBO Rep 2021 Oct 4:e53007. Epub 2021 Oct 4.

Research Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany.

While Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B-cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B-cell proliferation. Here, we combine biochemical, cellular, and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain, and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They exhibit enhanced transactivation capacities, accelerate the proliferation of infected B cells, and promote the development of monoclonal B-cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embr.202153007DOI Listing
October 2021

Microencapsulated Recombinant Human Epidermal Growth Factor Ameliorates Osteoarthritis in a Murine Model.

Evid Based Complement Alternat Med 2021 23;2021:9163279. Epub 2021 Sep 23.

Department of Orthopedics, Shuang Ho Hospital, New Taipei 235, Taiwan.

Osteoarthritis, a highly age-related and chronic inflammatory disorder with cartilage loss, causes patients difficultly in movement; there is no efficient and sustainable remedy for osteoarthritis currently. Although hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). In the current study, we induced the osteoarthritis-like symptoms with monosodium iodoacetate (MIA) in rats and investigated the therapeutic effects of Me-rhEGF. Following administration of HA/Me-rhEGF , we observed that the total Mankin scores, cartilage oligomeric protein, C-telopeptide of type II collagen, IL-1, IL-6, IL-17A, and TNF- cytokines, nitric oxide, and prostaglandin E2 expressions were significantly inhibited. Our results also strongly indicate that individual use of HA or rhEGF slightly decreased the inflammation and restored the destructive joint structure, but was not as drastic as seen in the HA/Me-rhEGF. Moreover, HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. These findings reveal that the treatment of HA/Me-rhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. In essence, we believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9163279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483914PMC
September 2021

Realizing Improved Sodium-Ion Storage by Introducing Carbonyl Groups and Closed Micropores into a Biomass-Derived Hard Carbon Anode.

ACS Appl Mater Interfaces 2021 Oct 29;13(40):47728-47739. Epub 2021 Sep 29.

Department of Chemistry, Fudan University, Shanghai 200433, China.

Micropores and defects, like oxygen-containing groups, as active sites for sodium-ion storage in hard carbon have attracted considerable attention; nevertheless, most oxygen doping or oxidizing processes inevitably introduce undesired oxygen groups into a carbon framework, leading to deteriorated initial Coulombic efficiency (ICE). Here, precise carbonyl groups and closed micropores are together introduced into biomass-derived hard carbon to enhance the Na-ion storage performance. The hard carbon delivers a large reversible capacity of 354.6 mA h g at 30 mA g, a high ICE (88.7%), as well as ultra-long cycling stability (277 mA h g at 0.3 A g over 1000 cycles; 243 mA h g at 1 A g over 5000 cycles). The rate capability and cycling stability of hard carbon in carbonate- and diglyme-based electrolytes are contrasted to demonstrate the superiority of diglyme. Cyclic voltammetry at varied scans and galvanostatic intermittent titration techniques are carried out to clarify the disparity between the two different electrolyte systems. Furthermore, the as-prepared hard carbon is utilized as the anode for sodium-ion full cells exhibiting an energy density of 166.2 W h kg at 0.2 C and a long-cycle life (47.9% retention over 200 cycles at 1 C).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c15884DOI Listing
October 2021

Radiosynthesis of 5-[F]Fluoro-1,2,3-triazoles through Aqueous Iodine-[F]Fluorine Exchange Reaction.

Molecules 2021 Sep 11;26(18). Epub 2021 Sep 11.

Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20892, USA.

In this report, a simple and efficient process to achieve fluorine-18-labeled 1,2,3-triazole is reported. The heteroaromatic radiofluorination was successfully achieved through an iodine-fluorine-18 exchange in an aqueous medium requiring only trace amounts of base and no azeotropic drying of fluorine-18. This methodology was optimized on a model reaction and further validated on multiple 1,2,3-triazole substrates with 18-60% radiochemical conversions. Using this strategy-the radiosynthesis of a triazole-based thiamin analogue-a potential positron emission tomography (PET) probe for imaging thiamin-dependent enzymes was synthesized with 10-16% isolated radiochemical yield (RCY) in 40 min (uncorrected, > 5).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26185522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469629PMC
September 2021

Expression of the NF-YB21 Encoded Gene Confers Tolerance to Osmotic Stresses in .

Int J Mol Sci 2021 Sep 10;22(18). Epub 2021 Sep 10.

State Key Laboratories of Agrobiotechnology, Department of Pomology, College of Horticulture, China Agricultural University, Beijing 100193, China.

Drought is the main environmental factor that limits the yield and quality of apples () grown in arid and semi-arid regions. Nuclear factor Ys (NF-Ys) are important transcription factors involved in the regulation of plant growth, development, and various stress responses. However, the function of genes is poorly understood in apples. Here, we identified 43 genes in the genome of apples and conducted an initial functional characterization of the apple . Expression analysis of members in revealed that a large number of were highly expressed in the roots compared with the leaves, and a large proportion of genes responded to drought treatment. Furthermore, heterologous expression of which was significantly upregulated by drought, led to a longer root length and, thus, conferred improved osmotic and salt tolerance in . Moreover, the physiological analysis of overexpression revealed enhanced antioxidant systems, including antioxidant enzymes and compatible solutes. In addition, genes encoding catalase (, ), superoxide dismutase (, , ), and peroxidase (, , , ) showed upregulated expression in the overexpression lines. These results for the gene family provide useful information for future studies on NF-Ys in apples, and the functional analysis of MsNF-YB21 supports it as a potential target in the improvement of apple drought tolerance via biotechnological strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22189777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467963PMC
September 2021

Quantitative Sound Speed Imaging of Cortical Bone and Soft Tissue: Results from Observational Data Sets.

IEEE Trans Med Imaging 2021 Sep 27;PP. Epub 2021 Sep 27.

This work presents the first quantitative ultrasonic sound speed images of ex vivo limb cross-sections containing both soft tissue and bone using Full Waveform Inversion (FWI) with level set (LS) and travel time regularization. The estimated bulk sound speed of bone and soft tissue are within 10% and 1%, respectively, of ground truth estimates. The sound speed imagery shows muscle, connective tissue and bone features. Typically, ultrasound tomography (UST) using FWI is applied to imaging breast tissue properties (e.g. sound speed and density) that correlate with cancer. With further development, UST systems have the potential to deliver volumetric operator independent tissue property images of limbs with non-ionizing and portable hardware platforms. This work addresses the algorithmic challenges of imaging the sound speed of bone and soft tissue by combining FWI with LS regularization and travel time methods to recover soft tissue and bone sound speed with improved accuracy and reduced soft tissue artifacts when compared to conventional FWI. The value of leveraging LS and travel time methods is realized by evidence of improved bone geometry estimates as well as promising convergence properties and reduced risk of final model errors due to un-modeled shear wave propagation. Ex vivo bulk measurements of sound speed and MRI cross-sections validates the final inversion results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TMI.2021.3115790DOI Listing
September 2021

Structure, Properties and Applications of Two-Dimensional Hexagonal Boron Nitride.

Adv Mater 2021 Sep 24:e2101589. Epub 2021 Sep 24.

Department of Materials Science and NanoEngineering, Rice University, 6100 Main St., Houston, TX, 77005, USA.

Hexagonal boron nitride (h-BN) has emerged as a strong candidate for two-dimensional (2D) material owing to its exciting optoelectrical properties combined with mechanical robustness, thermal stability, and chemical inertness. Super-thin h-BN layers have gained significant attention from the scientific community for many applications, including nanoelectronics, photonics, biomedical, anti-corrosion, and catalysis, among others. This review provides a systematic elaboration of the structural, electrical, mechanical, optical, and thermal properties of h-BN followed by a comprehensive account of state-of-the-art synthesis strategies for 2D h-BN, including chemical exfoliation, chemical, and physical vapor deposition, and other methods that have been successfully developed in recent years. It further elaborates a wide variety of processing routes developed for doping, substitution, functionalization, and combination with other materials to form heterostructures. Based on the extraordinary properties and thermal-mechanical-chemical stability of 2D h-BN, various potential applications of these structures are described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202101589DOI Listing
September 2021

"Oxynitride trap" over N/S co-doped graphene-supported catalysts promoting low temperature NH-SCR performance: Insight into the structure and mechanisms.

J Hazard Mater 2021 Sep 15;423(Pt B):127187. Epub 2021 Sep 15.

National Engineering Research Center of Chemical Fertilizer Catalyst, College of Chemical Engineering, Fuzhou University, Fuzhou 350002, PR China. Electronic address:

A series of nitrogen and sulfur (N/S) co-doped graphene supported catalysts (Mn-Ce-SnO/NSG) were synthesized using an in situ method for enhancing selective catalytic reduction of NO with NH (NH-SCR) performance. The changes in catalysts' structure, morphology, and active sites were systematically researched to explore the promoting effect of N/S co-doped on catalytic performance. The prepared Mn-Ce-SnO/NSG-0.3 catalyst achieves an excellent SCR activity at a low temperature, which is comparable to previous graphene-based catalysts. The Ce/(Ce + Ce), Mn/Mn, and O/(O + O) ratios in the catalyst are improved by N/S co-doping, which closely related to excellent SCR activity. Meanwhile, the unpaired electrons on N/S functional groups are effective in promoting the adsorption and further oxidation of gaseous NO. The ability to adsorb NH has also been promoted result of numerous Lewis acid sites over Mn-Ce-SnO/NSG-0.3. In-situ DRIFTS and reaction kinetic results suggest that the Eley-Rideal mechanism should be the most significant pathway in the temperature range of ≥ 200 °C, where coordinated NH has higher activity than ionic NH. The Langmuir-Hinshelwood (L-H) mechanism is the main route of the low-temperature (L-T) (< 200 °C) SCR reaction. Particularly, the L-T SCR activity improves because the N/S functional groups act as an additional "oxynitride trap" (based on the L-H mechanism).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.127187DOI Listing
September 2021

Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming.

Cell Metab 2021 Oct 23;33(10):2040-2058.e10. Epub 2021 Sep 23.

Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA; Division of Immunotherapy, The Hiram C. Polk, Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address:

One of the defining characteristics of a pre-metastatic niche, a fundamental requirement for primary tumor metastasis, is infiltration of immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDEs) polarize macrophages toward an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent, glycolytic-dominant metabolic reprogramming. TDE signaling through TLR2 and NF-κB leads to increased glucose uptake. TDEs also stimulate elevated NOS2, which inhibits mitochondrial oxidative phosphorylation resulting in increased conversion of pyruvate to lactate. Lactate feeds back on NF-κB, further increasing PD-L1. Analysis of metastasis-negative lymph nodes of non-small-cell lung cancer patients revealed that macrophage PD-L1 positively correlates with levels of GLUT-1 and vesicle release gene YKT6 from primary tumors. Collectively, our study provides a novel mechanism by which macrophages within a pre-metastatic niche acquire their immunosuppressive phenotype and identifies an important link among exosomes, metabolism, and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2021.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506837PMC
October 2021

An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.

Protein Cell 2021 Sep 23. Epub 2021 Sep 23.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; the Fifth People's Hospital of Shanghai; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology); Institutes of Biomedical Sciences; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13238-021-00871-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458794PMC
September 2021

Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.

Environ Epigenet 2021 17;7(1):dvab008. Epub 2021 Sep 17.

Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA.

Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eep/dvab008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424PMC
September 2021

Expanding the clinical spectrum of anti-IgLON5 disease: A multicenter retrospective study.

Eur J Neurol 2021 Sep 20. Epub 2021 Sep 20.

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

Background: We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease.

Methods: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes.

Results: The median age of onset for symptoms was 60 (range: 33-73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein-Barr virus (EBV)-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2).

Conclusions: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.15117DOI Listing
September 2021

Upregulation of miR‑335 exerts protective effects against sepsis‑induced myocardial injury.

Mol Med Rep 2021 11 20;24(5). Epub 2021 Sep 20.

Department of Clinic, Medicine School, Changsha Social Work College, Changsha, Hunan 410004, P.R. China.

Septicemia is associated with excessive inflammation, oxidative stress and apoptosis, causing myocardial injury that results in high mortality and disability rates worldwide. The abnormal expression of multiple microRNAs (miRNAs/miRs) is associated with more severe sepsis‑induced myocardial injury (SIMI) and miR‑335 has been shown to protect cardiomyocytes from oxidative stress. The present study aimed to investigate the role of miR‑335 in SIMI. An SIMI model was established by cecal ligation and puncture (CLP) in mice. An miRNA‑335 precursor (pre‑miR‑335) was transfected to accelerate miR‑335 expression and an miR‑335 inhibitor (anti‑miR‑335) was used to inhibit miR‑335 expression. CLP or sham surgery was performed on pre‑miR‑335, anti‑miR‑335 and wild‑type mice and miR‑335 expression was determined by reverse transcription‑quantitative PCR. Inflammatory factors (TNF‑α, IL‑6 and IL‑10) and troponin (cTNI), brain natriuretic peptide (BNP), creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were assessed using commercial kits. Apoptosis was detected by flow cytometry and cardiac function was assessed using a Langendorff isolated cardiac perfusion system. miR‑335 expression was upregulated and an elevation in inflammatory factors and cTNI, BNP, CK, LDH and AST was observed. Compared with the wild‑type control group, pre‑miR‑335 mice treated with CLP exhibited significantly reduced left ventricular development pressure, maximum pressure increased reduction rates, as well as decreased levels of TNF‑α, IL‑6 and IL‑10, myocardial injury and apoptosis; by contrast, these features were amplified in CLP‑treated anti‑miR‑335 mice. In conclusion, the upregulation of miR‑335 exerted ameliorative effects on myocardial injury following sepsis and may indicate a novel therapeutic intervention for SIMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.12446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477184PMC
November 2021

Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration.

Front Pharmacol 2021 31;12:711590. Epub 2021 Aug 31.

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY, United States.

Alcohol-associated liver disease (ALD) is the leading cause of liver disease worldwide, and alcohol-associated hepatitis (AH), a severe form of ALD, is a major contributor to the mortality and morbidity due to ALD. Many factors modulate susceptibility to ALD development and progression, including nutritional factors such as dietary fatty acids. Recent work from our group and others showed that modulation of dietary or endogenous levels of n6-and n3-polyunsaturated fatty acids (PUFAs) can exacerbate or attenuate experimental ALD, respectively. In the current study, we interrogated the effects of endogenous n3-PUFA enrichment in a mouse model which recapitulates features of early human AH using transgenic mice which endogenously convert n6-PUFAs to n3-PUFAs. Male wild type (WT) and littermates were provided an ethanol (EtOH, 5% v/v)-containing liquid diet for 10 days, then administered a binge of EtOH (5 g/kg) by oral gavage on the 11 day, 9 h prior to sacrifice. In WT mice, EtOH treatment resulted in liver injury as determined by significantly elevated plasma ALT levels, whereas in mice, EtOH caused no increase in this biomarker. Compared to their pair-fed controls, a significant EtOH-mediated increase in liver neutrophil infiltration was observed also in WT, but not mice. The hepatic expression of several cytokines and chemokines, including , was significantly lower in WT EtOH-challenged mice. Cultured bone marrow-derived macrophages isolated from mice expressed less and (a canonical neutrophil chemoattractant) mRNA compared to WT when stimulated with lipopolysaccharide. Further, we observed decreased pro-inflammatory M1 liver tissue-resident macrophages (Kupffer cells, KCs), as well as increased liver T regulatory cells in WT EtOH-fed mice. Taken together, our data demonstrated protective effects of endogenous n3-PUFA enrichment on liver injury caused by an acute-on-chronic EtOH exposure, a paradigm which recapitulates human AH, suggesting that n3-PUFAs may be a viable nutritional adjuvant therapy for this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.711590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438569PMC
August 2021

Identification of a novel mutation in with functional analysis in a cohort of 516 familial patients with exudative vitreoretinopathy.

Mol Vis 2021 1;27:528-541. Epub 2021 Sep 1.

Department of Ophthalmology, Xinhua Hospital, Affiliated to Medicine School of Shanghai Jiaotong University, No. 1665, Kongjiang Road, Shanghai, China.

Purpose: To identify a novel mutation in with clinical and functional analysis among 516 familial patients with exudative vitreoretinopathy (FEVR).

Methods: Next-generation sequencing was performed on 516 patients with FEVR between January 2015 and October 2017. Clinical data were collected from patient charts, including sex, age at presentation, visual acuity if available, axial length, stage, and systemic clinical findings. Protein and mRNA levels were detected with western blotting and real-time quantitative PCR, respectively. Mass spectrometry was used to analyze the interacting protein of KIF11.

Results: In total, 304 of 516 patients were identified with at least one mutation in FEVR causative genes. Mutations in were identified in 14.47% of all carriers. The novel mutation p. H718L accounted for the greatest proportion (12/44; 27.30%) among all mutations in . Fundus presentations in these 12 individuals varied from the avascular zone of the peripheral retina to total retinal detachment. The p. H718L mutation can reduce the proliferation of human retinal endothelial cells (HRECs) compared to the wild type. The mRNA level of vascular endothelial growth factor-α, transforming growth factor-α, metalloproteinase-1, and angiopoietin-like 4 were depressed in the (p. H718L) groups under hypoxia stimuli. Mass spectrometry results demonstrated that eukaryotic elongation factor 2 (EEF2) was an interacting protein of KIF11 and that the p. H718L mutation can attenuate the binding activity.

Conclusions: Patients with the most frequent mutation p. H718L showed typical FEVR presentations in this cohort. The mutation in likely plays a role in the proliferation of HRECs, and the p. H718L mutation can reduce the proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410233PMC
September 2021

Polymorphisms in the gene significantly affect the pharmacokinetics of sirolimus after kidney transplantation.

Pharmacogenomics 2021 Sep 15;22(14):903-912. Epub 2021 Sep 15.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, PR China.

Sirolimus (SIR) is an immunosuppressant with limitations, including a narrow treatment window, multiple adverse reactions and large differences within and among individuals. The correlation between numerous SNPs and SIR in terms of trough concentration in the early stage after kidney transplantation was analyzed. A retrospective cohort study involving 69 kidney transplantation recipients was designed. Blood samples were collected to extract total DNAs, and trough SIR concentrations were measured. Logistic regression was used to analyze the association between SNPs and SIR trough concentrations. At 7 days, 1 month and 3 months, the mean SIR trough concentration of patients in the rs4646453-CC group was significantly higher than that in the rs4646453-AA and rs4646453-CA groups (p < 0.001) and rs15524-AA group was significantly higher than that in the rs15524-AG and rs15524-GG groups (p < 0.001). Our study indicated that both rs4646453 and rs15524 had a certain influence on SIR trough concentration at 7 days, 1 month and 3 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/pgs-2021-0083DOI Listing
September 2021

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Int J Med Sci 2021 27;18(15):3581-3587. Epub 2021 Aug 27.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP. Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (=58) and premature infants without ROP (=25), and KEGG pathway analysis was used to identify the involved pathways. Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis. The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.63603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436098PMC
August 2021

Activated Natural Killer Cell Promotes Nonalcoholic Steatohepatitis Through Mediating JAK/STAT Pathway.

Cell Mol Gastroenterol Hepatol 2021 Sep 18. Epub 2021 Sep 18.

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Background & Aims: Hepatic immune microenvironment plays a pivotal role in the development of nonalcoholic steatohepatitis (NASH). However, the role of natural killer (NK) cells, accounting for 10%-20% of liver lymphocytes, in NASH is still unclear. In this study, we aim to investigate the functional significance of NK cells in NASH evolution.

Methods: NASH was induced in mice fed methionine- and choline-deficient diet (MCD), choline-deficient high-fat diet (CD-HFD), or high-fat diet with streptozotocin injection (STAM model). NK cell deficient mice (Nfil3) and neutralization antibody (PK136) were used in this study.

Results: Activated liver NK cells were identified with increased expression of NKG2D, CD107a, and interferon-γ but decreased inhibitory NKG2A. With NK cell deficiency Nfil3 mice, the absence of NK cells ameliorated both MCD- and CDHF- induced NASH development with significantly decreased hepatic triglycerides, peroxides, alanine aminotransferase, and aspartate aminotransferase compared with Nfil3 mice. Further molecular analysis unveiled suppressed pro-inflammatory cytokines and associated signaling. Mechanistically, NK cells isolated from NASH liver secreted higher levels of pro-inflammatory cytokines (interferon-γ, interleukin 1β, interleukin 12, CCL4, CCL5, and granulocyte-macrophage colony-stimulating factor), which could activate hepatic JAK-STAT1/3 and nuclear factor kappa B signaling and induce hepatocyte damage evidenced by elevated reactive oxygen species and apoptosis rate. Moreover, neutralization antibody PK136-dependent NK cell depletion can significantly alleviate MCD-induced steatohepatitis with suppressed cytokine levels and JAK-STAT1/3 activity.

Conclusions: NK cells in NASH liver are activated with a more pro-inflammatory cytokine milieu and promote NASH development via cytokine-JAK-STAT1/3 axis. Modulation of NK cells provides a potential therapeutic strategy for NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2021.08.019DOI Listing
September 2021

Controllably Doping Nitrogen into 1T/2H MoS Heterostructure Nanosheets for Enhanced Supercapacitive and Electrocatalytic Performance by Low-Power N Plasma.

ACS Appl Mater Interfaces 2021 Sep 10;13(37):44427-44439. Epub 2021 Sep 10.

The State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

Molybdenum disulfide (MoS) is a promising candidate for use as a supercapacitor electrode material and non-noble-metal electrocatalyst owing to its relatively high theoretical specific capacitance, Pt-like electronic feature, and graphene-like structure. However, insufficient electrochemically active sites along with poor conductivity significantly hinder its practical application. Heteroatom doping and phase engineering have been regarded as effective ways to overcome the inherent limitations of MoS and enhance its ion storage and electrocatalytic performance. In this study, a plasma-assisted nitrogen-doped 1T/2H MoS heterostructure has been proposed for the first time, resulting in excellent supercapacitor performance and hydrogen evolution reaction activity. XPS, Raman, and TEM analysis results indicate that N atoms have been successfully doped into MoS nanosheets via room-temperature low-power N plasma, and the 1T/2H hybrid phase is maintained. As expected, the 1T/2H MoS heterostructure after a 10 min plasma treatment displayed a much boosted supercapacitive performance with a high specific capacitance of 410 F g at 1 A g and an excellent hydrogen evolution property with a low overpotential of 131 mV vs RHE at 10 mA cm for hydrogen evolution reaction. The excellent performance is superior to most of the recently reported outstanding MoS-based electrode and electrocatalytic materials. Moreover, the as-assembled flexible symmetric supercapacitor shows a high specific capacitance of 84.8 F g and superior mechanical robustness with 84.5% capacity retention after 2000 bending cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c12973DOI Listing
September 2021

Hierarchical Dynamical Model for Multiple Cortical Neural Decoding.

Neural Comput 2021 04;33(5):1372-1401

Department of Electronic and Computer Engineering and Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR 999077, China

Motor brain machine interfaces (BMIs) interpret neural activities from motor-related cortical areas in the brain into movement commands to control a prosthesis. As the subject adapts to control the neural prosthesis, the medial prefrontal cortex (mPFC), upstream of the primary motor cortex (M1), is heavily involved in reward-guided motor learning. Thus, considering mPFC and M1 functionality within a hierarchical structure could potentially improve the effectiveness of BMI decoding while subjects are learning. The commonly used Kalman decoding method with only one simple state model may not be able to represent the multiple brain states that evolve over time as well as along the neural pathway. In addition, the performance of Kalman decoders degenerates in heavy-tailed nongaussian noise, which is usually generated due to the nonlinear neural system or influences of movement-related noise in online neural recording. In this letter, we propose a hierarchical model to represent the brain states from multiple cortical areas that evolve along the neural pathway. We then introduce correntropy theory into the hierarchical structure to address the heavy-tailed noise existing in neural recordings. We test the proposed algorithm on in vivo recordings collected from the mPFC and M1 of two rats when the subjects were learning to perform a lever-pressing task. Compared with the classic Kalman filter, our results demonstrate better movement decoding performance due to the hierarchical structure that integrates the past failed trial information over multisite recording and the combination with correntropy criterion to deal with noisy heavy-tailed neural recordings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1162/neco_a_01380DOI Listing
April 2021

Lactate and Myocadiac Energy Metabolism.

Front Physiol 2021 17;12:715081. Epub 2021 Aug 17.

Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia.

The myocardium is capable of utilizing different energy substrates, which is referred to as "metabolic flexibility." This process assures ATP production from fatty acids, glucose, lactate, amino acids, and ketones, in the face of varying metabolic contexts. In the normal physiological state, the oxidation of fatty acids contributes to approximately 60% of energy required, and the oxidation of other substrates provides the rest. The accumulation of lactate in ischemic and hypoxic tissues has traditionally be considered as a by-product, and of little utility. However, recent evidence suggests that lactate may represent an important fuel for the myocardium during exercise or myocadiac stress. This new paradigm drives increasing interest in understanding its role in cardiac metabolism under both physiological and pathological conditions. In recent years, blood lactate has been regarded as a signal of stress in cardiac disease, linking to prognosis in patients with myocardial ischemia or heart failure. In this review, we discuss the importance of lactate as an energy source and its relevance to the progression and management of heart diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.715081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415870PMC
August 2021

Association between high BMI and high homocysteine levels in Chinese patients with bipolar disorder.

J Affect Disord 2021 Aug 27;295:284-290. Epub 2021 Aug 27.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, Beijing, China. Electronic address:

Background: Bipolar disorder (BD) has been associated with an increased prevalence of weight gain and abnormally elevated plasma homocysteine (Hcy) levels. However, the relationship between BMI and Hcy in BD patients has not been investigated. This study aimed to explore this relationship in Chinese patients with BD.

Methods: Plasma Hcy levels, socio-demographic parameters, clinical and anthropometric data were collected from 195 BD inpatients and 84 healthy controls. The level of plasma Hcy was determined by high-performance liquid chromatography. Body mass index (BMI) was calculated by body weight divided by the square of the height. The participants were divided into a high BMI group and a low BMI group using 24 kg/m as a threshold.

Results: The prevalence of high BMI was slightly elevated in BD patients in comparison to healthy controls. Patients with elevated BMI had significantly higher Hcy levels than patients with low BMI. Hcy level was an independent contributor of the occurrence of high BMI in BD patients. The level of Hcy was positively correlated with BMI in BD patients. In addition, depressive episodes of BD were positively correlated with the prevalence of high BMI and married BD patients were more likely to have high BMI levels.

Conclusions: There is a close relationship between BMI and plasma Hcy levels in patients with BD, suggesting that Hcy may be an important indicator for BD-induced weight gain. This finding provides a new avenue for weight management of BD patients and to help avoid the potential risk of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.08.032DOI Listing
August 2021

Epstein-Barr virus and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation in patients with non-Hodgkin lymphoma: the prevalence and impacts on outcomes : EBV and CMV reactivation post allo-HCT in NHL.

Ann Hematol 2021 Nov 4;100(11):2773-2785. Epub 2021 Sep 4.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, 215006, China.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations are common complications after allogeneic hematopoietic cell transplantation (allo-HCT), but data focusing on non-Hodgkin lymphoma (NHL) are limited. We retrospectively analyzed the prevalence of EBV and CMV reactivation post-allo-HCT and the impacts on transplant outcomes in 160 NHL patients. The 1-year incidences of EBV and CMV reactivation were 22.58% and 25.55%, respectively. Independent impactors for EBV reactivation were more than 6 lines of chemotherapy (P = 0.030), use of rituximab (P = 0.004), and neutrophil recovery within 30 days post-HCT (P = 0.022). For T-cell lymphoblastic lymphoma patients, the International Prognostic Index (IPI) (P = 0.015) and chronic GVHD (P = 0.001) increased the risk of CMV reactivation. CMV reactivation was independently related to a lower risk of relapse (P = 0.027) but higher transplant-related mortality (TRM) (P = 0.038). Although viral reactivation had no significant impact on overall survival (OS) in the whole cohort, it led to an inferior 2-year OS (67.6% versus 92.5%, P = 0.005) and TRM (20.1% versus 4.7%, P = 0.020) in recipients surviving for more than 180 days. We concluded that EBV and CMV reactivation post-allotransplant still deserved concern particularly in NHL patients with high-risk factors, since it is generally related to a deteriorated prognosis. Large-scale studies are warranted to validate our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04642-5DOI Listing
November 2021
-->