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1.
Lancet Infect Dis ; 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38878787

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

2.
ChemSusChem ; : e202400704, 2024 Jun 11.
Article En | MEDLINE | ID: mdl-38860330

The biosynthesis of valuable plant-derived monoterpene (-)-menthol from readily available feedstocks (e.g., (-)-limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)-pulegone into (-)-menthone, the (-)-menthol precursor, through (+)-pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2-1 (A50V/G53W), was obtained, showing respective 20-fold and 204-fold improvements in specific activity and catalytic efficiency. PrPGRM2-1 was employed to bioreduce (+)-pulegone, resulting in 4.4-fold and 35-fold enhancements in (-)-menthone titers compared with the bioreductions catalyzed by wild-type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole-cell biocatalyst containing PrPGRM2-1, MpMMR, and BstFDH was constructed and achieved the highest (-)-menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (-)-menthol biosynthesis.

3.
Angew Chem Int Ed Engl ; 62(10): e202217839, 2023 Mar 01.
Article En | MEDLINE | ID: mdl-36631412

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

4.
Nanoscale ; 14(48): 18200-18208, 2022 Dec 15.
Article En | MEDLINE | ID: mdl-36465000

It is well known that the introduction of exposed fluorine (F) sites into metal-organic frameworks (MOFs) can effectively promote acetylene (C2H2) adsorption via C-H⋯F hydrogen bonds. However, such super strong hydrogen bonding interactions usually lead to very high acetylene adsorption enthalpy and thus require more energy during the adsorbent regeneration process. As the same group elements, chlorine (Cl), bromine (Br) and iodine (I) also can act as hydrogen bond acceptors but with relatively weak forces. So, it is speculated that the decoration of Cl, Br or I sites on the pore surface of MOF adsorbents may enhance acetylene adsorption but with lower energy consumption. Herein, ultra-microporous MOFs constructed by Cu4X4 (X = Cl, Br, I) motifs and 1,2,4-triazolate linkers, namely, [Cu8X4(TRZ)4]n (TRZ = 3,5-diethyl-1,2,4-triazole or detrz for SNNU-313-X, and 3,5-dipropyl-1,2,4-triazole or dptrz for SNNU-314-X), provide an ideal platform to investigate the effect of C-H⋯X (X = Cl, Br, I) hydrogen bonding on C2H2 adsorption and purification performance. Benefiting from the small pore size and pore environment, the C2H2 uptake and separation properties of this series of MOFs are systematically regulated. Detailed gas adsorption results show that with the same organic linker, the C2H2 uptake and separation (C2H2/C2H4 and C2H2/CO2) performance decrease clearly with the electronegativity of halogen ions (SNNU-313-Cl > SNNU-313-Br > SNNU-313-I). With the same halogen ion, the gas adsorption decreases with the bulk of decorated alkyl groups (SNNU-313-Cl > SNNU-314-Cl). Remarkably, SNNU-313/314 series MOF adsorbents exhibit moderate C2H2 uptake capacity and high separation ability, but the C2H2 adsorption enthalpies are much lower than those of MOF materials with exposed F sites. Dynamic fixed-bed column breakthrough experiments and Grand Canonical Monte Carlo (GCMC) simulations further indicate the critical effects of halogen hydrogen bonds on acetylene adsorption and separation. Overall, this work demonstrated an effective regulation of acetylene adsorption and separation by rational C-H⋯X hydrogen bonding, which may provide a new route for the exploration of energy-efficient acetylene adsorbent materials.

5.
Appl Environ Microbiol ; 88(9): e0034122, 2022 05 10.
Article En | MEDLINE | ID: mdl-35442081

Isopropanol dehydrogenase (IPADH) is one of the most attractive options for nicotinamide cofactor regeneration due to its low cost and simple downstream processing. However, poor thermostability and strict cofactor dependency hinder its practical application for bioconversions. In this study, we simultaneously improved the thermostability (433-fold) and catalytic activity (3.3-fold) of IPADH from Brucella suis via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H) by 1.23 × 106-fold. When these variants were employed in three typical bioredox reactions to drive the synthesis of important chiral pharmaceutical building blocks, they outperformed the commonly used cofactor regeneration systems (glucose dehydrogenase [GDH], formate dehydrogenase [FDH], and lactate dehydrogenase [LDH]) with respect to efficiency of cofactor regeneration. Overall, our study provides two promising IPADH variants with complementary cofactor specificities that have great potential for wide applications. IMPORTANCE Oxidoreductases represent one group of the most important biocatalysts for synthesis of various chiral synthons. However, their practical application was hindered by the expensive nicotinamide cofactors used. Isopropanol dehydrogenase (IPADH) is one of the most attractive biocatalysts for nicotinamide cofactor regeneration. However, poor thermostability and strict cofactor dependency hinder its practical application. In this work, the thermostability and catalytic activity of an IPADH were simultaneously improved via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H). The resultant variants show great potential for regeneration of nicotinamide cofactors, and the engineering strategy might serve as a useful approach for future engineering of other oxidoreductases.


NAD , Niacinamide , 2-Propanol , Formate Dehydrogenases/genetics , NADP , Regeneration
6.
Zool Res ; 43(1): 52-63, 2022 01 18.
Article En | MEDLINE | ID: mdl-34821086

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.


Chiroptera , Hot Temperature , Seasons , TRPC Cation Channels , Animals , Chiroptera/genetics , Female , Hibernation/genetics , Male , Mice , TRPC Cation Channels/genetics , TRPV Cation Channels/genetics
7.
World J Clin Cases ; 9(32): 9783-9791, 2021 Nov 16.
Article En | MEDLINE | ID: mdl-34877317

BACKGROUND: Severe bony Bankart lesions are a difficult challenge in clinical treatment and research. The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures. While good results have been achieved, there are also complications such as coracoid fracture, bone graft displacement, and vascular and nerve injury. AIM: To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions. METHODS: Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used. When the humeral rotation angles were 0°, 30°, 60° and 90°, and the axial loads were 30 N, 40 N, and 50 N, the humerus displacement was studied by biomechanical experiments. RESULTS: When the angle of external rotation of the humerus was 0°, 30°, 60°, and 90°, with axial loads of 30 N, 40 N, and 50 N, the data of the normal control group, allograft pin repair group, and titanium alloy hollow screw repair group were compared with each other by the q-test, which showed that there were no statistically differences among the three groups (P > 0.05). CONCLUSION: The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability. The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

8.
Inorg Chem ; 60(23): 18473-18482, 2021 Dec 06.
Article En | MEDLINE | ID: mdl-34797628

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

9.
Sensors (Basel) ; 21(19)2021 Sep 30.
Article En | MEDLINE | ID: mdl-34640891

To construct circular barrier coverage (CBC) with multistatic radars, a deployment optimization method based on equipartition strategy is proposed in this paper. In the method, the whole circular area is divided into several sub-circles with equal width, and each sub-circle is blanketed by a sub-CBC that is built based on the multistatic radar deployment patterns. To determine the optimal deployment patterns for each sub-CBC, the optimization conditions are firstly studied. Then, to optimize the deployment of the whole circular area, a model based on minimum deployment cost is proposed, and the proposed model is divided into two sub-models to solve the optimization issue. In the inner model, it is assumed that the width of a sub-circle is given. Based on the optimization conditions of the deployment pattern, integer linear programming (ILP) and exhaustive method (EM) are jointly adopted to determine the types and numbers of deployment patterns. Moreover, a modified formula is introduced to calculate the maximum valid number of receivers in a pattern, thus narrowing the search scope of the EM. In the outer model, the width of a sub-circle is assumed to be a variable, and the EM is adopted to determine the minimum total deployment cost and the optimal deployment patterns on each sub-circle. Moreover, the improved formula is exploited to determine the range of width for a sub-circle barrier and reduce the search scope of the EM. Finally, simulations are conducted in different conditions to verify the effectiveness of the proposed method. The simulation results indicate that the proposed method can spend less deployment cost and deploy fewer transmitters than the state-of-the-artwork.

10.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118855, 2021 01.
Article En | MEDLINE | ID: mdl-32926941

Dysfunctions of vascular smooth muscle cells (VSMCs) play crucial roles in vascular remodeling in hypertension, which correlates with pathologically elevated cyclic stretch due to increased arterial pressure. Recent researches reported that autophagy, a life-sustaining process, was increased in hypertension. However, the mechanobiological mechanism of VSMC autophagy and its potential roles in vascular remodeling are still unclear. Using renal hypertensive rats in vivo and FX5000 stretch application Unit in vitro, the autophagy of VSMCs was detected. The results showed that LC3II remarkably enhanced in hypertensive rats and 15% cyclic stretch (mimic the pathologically increased mechanical stretch in hypertension), and the activity of mammalian target of rapamycin (mTOR) was suppressed in 15% cyclic stretch. Administration of autophagy inhibitors, bafilomycin A1 and chloroquine, repressed VSMC proliferation efficiently, but did not affect the degradation of two important nuclear envelope (NE) proteins, lamin A/C and emerin. Using RNA interference to decline the expression of lamin A/C and emerin, respectively, we discovered that autophagy was upregulated under both static and 5% cyclic stretch conditions, accompanying with the decreased mTOR activity. During 15% cyclic stretch application, mTOR inhibition was responsible for autophagy elevation. Chloroquine administration in vivo inhibited the expression of PCNA (marker of proliferation) of abdominal aorta in hypertensive rats. Altogether, these results demonstrated that pathological cyclic stretch suppresses the expression of lamin A/C and emerin which subsequently represses mTOR pathway so as to induce autophagy activation. Blocking autophagic flux may be a practicable way to relieve the pathological vascular remodeling in hypertensive.


Autophagy/genetics , Hypertension/genetics , Lamin Type A/genetics , Membrane Proteins/genetics , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Nuclear Proteins/genetics , Animals , Cell Proliferation/drug effects , Chloroquine/pharmacology , Hypertension/drug therapy , Hypertension/pathology , Male , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Nuclear Envelope/genetics , Rats , Signal Transduction/genetics , TOR Serine-Threonine Kinases/genetics , Vascular Remodeling/drug effects
11.
Clin Lung Cancer ; 22(1): e98-e111, 2021 01.
Article En | MEDLINE | ID: mdl-33067127

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.


Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Mutation , Protein Kinase Inhibitors/therapeutic use , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Follow-Up Studies , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate
12.
Inorg Chem ; 59(22): 16725-16736, 2020 Nov 16.
Article En | MEDLINE | ID: mdl-33152248

Both methane (CH4) and acetylene (C2H2) are important energy source and raw chemicals in many industrial processes. The development of an energy-efficient and environmentally friendly separation and purification strategy for CH4 and C2H2 is necessary. Ultramicroporous metal-organic framework (MOF) materials have shown great success in the separation and purification of small-molecule gases. Herein, the synergy effect of tritopic polytetrazolate and ditopic terephthalate ligands successfully generates a series of isoreticular ultramicroporous cadmium tetrazolate-carboxylate MOF materials (SNNU-13-16) with excellent CH4 and C2H2 purification performance. Except for the uncoordinated tetrazolate N atoms serving as Lewis base sites, the pore size and pore surface of MOFs are systematically engineered by regulating dicarboxylic acid ligands varying from OH-BDC (SNNU-13) to Br-BDC (SNNU-14) to NH2-BDC (SNNU-15) to 1,4-NDC (SNNU-16). Benefiting from the ultramicroporous character (3.8-5.9 Å), rich Lewis base N sites, and tunable pore environments, all of these ultramicroporous MOFs exhibit a prominent separation capacity for carbon dioxide (CO2) or C2 hydrocarbons from CH4 and C2H2. Remarkably, SNNU-16 built by 1,4-NDC shows the highest ideal adsorbed solution theory CO2/CH4, ethylene (C2H4)/CH4, and C2H2/CH4 separation selectivity values, which are higher than those of most famous MOFs with or without open metal sites. Dynamic breakthrough experiments show that SNNU-16 can also efficiently separate the C2H2/CO2 mixtures with a gas flow rate of 4 mL min-1 under 1 bar and 298 K. The breakthrough time (18 min g-1) surpasses most best-gas-separation MOFs and nearly all other metal azolate-carboxylate MOF materials under the same conditions. The above prominently CH4 and C2H2 purification abilities of SNNU-13-16 materials were further confirmed by the Grand Canonical Monte Carlo (GCMC) simulations.

13.
Sheng Li Xue Bao ; 72(4): 506-512, 2020 Aug 25.
Article Zh | MEDLINE | ID: mdl-32820313

Alzheimer's disease (AD) is currently the most prevalent neurodegenerative disease in the aging population. It is characterized by massive deposition of extracellular ß-amyloid peptide and formation of intracellular neurofibrillary tangles. Cancer is also an age-related disease. Some epidemiological studies have shown an inverse relationship between AD and the onset of various types of cancers, that is, the risk of cancer in patients with AD is reduced, and vice versa. Epigenetic mechanisms play important roles in the development of AD and cancer. In this article, we will review the recent research advances on the epigenetic mechanisms of AD and cancer onset, and provide new ideas for rethinking the relevance of AD and cancer with a "holistic concept".


Alzheimer Disease , Neoplasms , Neurodegenerative Diseases , Aged , Epigenesis, Genetic , Humans , Neurofibrillary Tangles
14.
ACS Appl Mater Interfaces ; 12(22): 24786-24795, 2020 Jun 03.
Article En | MEDLINE | ID: mdl-32372639

As an important organic intermediate, benzonitrile (BN) is widely involved in organic synthetic chemistry and pharmaceutical and dyestuff industries. However, the exploration of a more efficient and controllable synthesis technique and the corresponding greener catalysts for the synthesis of BN still poses a great challenge. Herein, with multimetallic two-dimensional conductive metal-organic frameworks (2D cMOF) as anodic electrocatalysts, we develop a green, convenient, and highly efficient electrochemical synthesis strategy for BN. Thanks to the intrinsic 2D electrically conductive structure and the optimized the multimetallic coupling catalytic effect, the resulting multimetallic 2D cMOFs exhibit excellent benzylamine (BA) electrooxidation performance. Especially, the trimetallic 2D cMOF (NiCoFe-CAT) requires an ultralow potential of 1.29 V vs reversible hydrogen electrode (RHE) to achieve a 10 mA·cm-2 current density, which indicates the fastest reaction and the most favorable thermodynamic condition. A very high yield (0.058 mmol·mg-1·h-1) and faradic efficiency (∼87%) of benzonitrile are both achieved during the BA electrooxidation reaction at 1.45 V. The reaction mechanism investigations indicated that the various redox mediators of MII/MIII (Ni, Co, Fe) may be regarded as multimetal active species to promote BA conversion. Also, the excellent cycling durability of multimetallic 2D cMOFs further promotes their potential practical applications. These electrocatalytic performances are considered excellent and nearly surpass all other reported Ni-based inorganics or MOF-based electrocatalysts for the electrocatalytic oxidation of benzylamine.

15.
Natl Sci Rev ; 7(6): 952-963, 2020 Jun.
Article En | MEDLINE | ID: mdl-34692117

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

16.
Acta Physiol (Oxf) ; 228(3): e13374, 2020 03.
Article En | MEDLINE | ID: mdl-31495066

AIM: Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodelling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano-responsive, but the role of lamin A/C in VSMC apoptosis is still unclear. METHODS: FX-5000T Strain Unit provided cyclic stretch (CS) in vitro. AnnexinV/PI and cleaved Caspase 3 ELISA detected apoptosis. qPCR was used to investigate the expression of miR-124-3p and a luciferase reporter assay was used to evaluate the ability of miR-124-3p binding to the Lmna 3'UTR. Protein changes of lamin A/C and relevant molecules were detected using western blot. Ingenuity Pathway Analysis and Protein/DNA array detected the potential transcription factors. Renal hypertensive rats verified these changes. RESULTS: High cyclic stretch (15%-CS) induced VSMC apoptosis and repressed lamin A/C expressions compared with normal (5%-CS) control. Downregulation of lamin A/C enhanced VSMC apoptosis. In addition, 15%-CS had no significant effect on mRNA expression of Lmna, and lamin A/C degradation was not induced by autophagy. 15%-CS elevated miR-124-3p bound to the 3'UTR of Lmna and negatively regulated protein expression of lamin A/C. Similar changes occurred in renal hypertensive rats compared with sham controls. Lamin A/C repression affected activity of TP53, CREB1, MYC, STAT1/5/6 and JUN, which may in turn affect apoptosis. CONCLUSION: Our data suggested that the decreased expression of lamin A/C upon abnormal cyclic stretch and hypertension may induce VSMC apoptosis. These mechano-responsive factors play important roles in VSMC apoptosis and might be novel therapeutic targets for vascular remodelling in hypertension.


Hypertension/pathology , Lamin Type A/antagonists & inhibitors , MicroRNAs/genetics , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Animals , Apoptosis/physiology , Cells, Cultured , Disease Models, Animal , Hypertension/genetics , Hypertension/metabolism , Male , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Stress, Mechanical
17.
ACS Appl Mater Interfaces ; 12(4): 4432-4442, 2020 Jan 29.
Article En | MEDLINE | ID: mdl-31838854

It is well-known that the formation of ferroalloy with the addition of the second or third metal during the steel-making process usually can improve the performance of the iron. Inspired by ferroalloy materials, it is speculated that the pore environment, framework charge, and catalytic properties of metal-organic frameworks (MOFs) could be optimized dramatically via the introduction of ferroalloy-like inorganic building blocks. However, different to ferroalloy, the accurate integration of different metals into one MOF platform is still challenging. Herein, taking advantages of the good compatibility for metals in trigonal prismatic trinuclear cluster, a series of Fe-based alloy-like [M3O(O2C)6] motifs (M3 = Fe3, Fe1.5Ni1.5, Fe1.5Co1.5, Fe1.5Ti1.5, FeCoNi, and FeTiCo) are successfully generated, which further lead to a robust Fe-MOF material family (SNNU-5s). These multicomponent MOFs not only provide a good chance to explore the impact of pore environment on gas adsorption/separation but also offer an opportunity to the efficient electrocatalytic reaction directly. Accordingly, compared with the SNNU-5-Fe parent structure, the pore characters of heterometallic SNNU-5 MOFs are clearly regulated by the type of alloy-like building blocks. SNNU-5-FeTi displays more superior gas separation performance for CO2/CH4, C2H2/CH4, C2H4/CH4, and C2H2/CO2 gas mixtures. What is more, benefited from the multimetallic active sites and their catalytic synergy, FeCoNi-ternary alloy-like cluster-based SNNU-5 MOF material exhibits an exceptional oxygen evolution reaction activity in aqueous solution at pH = 13, which delivers a low overpotential (ηj=10 = 317 mV), a fast reaction kinetics (Tafel slope = 37 mV dec-1), and excellent catalytic stability. This facile multialloy-like building block strategy holds promise to accurately design and improve the performance of MOFs, as well as open an avenue to understand the related mechanisms.

18.
Angew Chem Int Ed Engl ; 58(38): 13590-13595, 2019 Sep 16.
Article En | MEDLINE | ID: mdl-31407503

A strategy called ultramicroporous building unit (UBU) is introduced. It allows the creation of hierarchical bi-porous features that work in tandem to enhance gas uptake capacity and separation. Smaller pores from UBUs promote selectivity, while larger inter-UBU packing pores increase uptake capacity. The effectiveness of this UBU strategy is shown with a cobalt MOF (denoted SNNU-45) in which octahedral cages with 4.5 Špore size serve as UBUs. The C2 H2 uptake capacity at 1 atm reaches 193.0 cm3 g-1 (8.6 mmol g-1 ) at 273 K and 134.0 cm3 g-1 (6.0 mmol g-1 ) at 298 K. Such high uptake capacity is accompanied by a high C2 H2 /CO2 selectivity of up to 8.5 at 298 K. Dynamic breakthrough studies at room temperature and 1 atm show a C2 H2 /CO2 breakthrough time up to 79 min g-1 , among top-performing MOFs. Grand canonical Monte Carlo simulations agree that ultrahigh C2 H2 /CO2 selectivity is mainly from UBU ultramicropores, while packing pores promote C2 H2 uptake capacity.

19.
Inorg Chem ; 58(16): 11220-11230, 2019 Aug 19.
Article En | MEDLINE | ID: mdl-31368311

The detection of nitro compounds and removal of organic dyes remain urgent issues because they are poisonous to humans. Taking advantage of metal-organic framework (MOF) materials, we demonstrate herein an indium-organic framework (InOF) exhibiting sensitive fluorescence sensing of nitro compounds, prominent dye capture, and excellent photodegradation of dyes. By using 4,4',4″-s-triazine-1,3,5-triyltri-p-aminobenzoate (TATAB), an amino-functionalized BTB-like linker, the 3D SNNU-110 structure ({[In3OCl(H2O)2(TATAB)2]}n) is formed. SNNU-110 shows a 3,6-connected 3,6T22 topology with TATAB and [In3O(CO2)6] tricapped trigonal-prismatic clusters as 3- and 6-connected nodes. Thanks to the fluorescence properties and amine recognition sites of TATAB, SNNU-110 exhibits excellent performance of fluorescence quenching for six electron-deficient nitroaromatics. The intercrossing 1D channels in SNNU-110 formed from the a- and b-axis directions with dimensions of about 18 Å × 11 Å can capture diverse cationic, anionic, or neutral dyes effectively. What is more, the existence of an inorganic [In3O] cluster enable SNNU-110 to be a good photocatalyst. Upon irradiation with a 300 W xenon lamp, SNNU-110 shows outstanding photocatalytic activity toward rhodamine B (RhB) and methylene blue (MB), and there was almost no degradation. The catalytic activity can retain about 94.6% (RhB) and 93.1% (MB), respectively. Overall, SNNU-110 fully demonstrates the power of multicomponent MOFs, which provide a feasible route for the design of functional materials toward to pollutant identification and removal applications.

20.
J Clin Neurosci ; 65: 125-133, 2019 Jul.
Article En | MEDLINE | ID: mdl-31036506

The present study focused on the novel roles and the underlying mechanisms of miR-135b in pyroptosis of MPP+-induced Parkinson's disease (PD). We established an in vitro PD model induced by MPP+. Our results demonstrated miR-135b was lower while FoxO1 was inversely higher in MPP+-treated SH-SY5Y and PC-12 cells. Luciferase reporter assay showed FoxO1 was a downstream target of miR-135b. MiR-135b mimics suppressed MPP+-induced pyroptosis and the upregulation of TXNIP, NLRP3, Caspase-1, ASC, GSDMDNterm and IL-1ß. Moreover, FoxO1 overexpression had no effect on miR-135b but reversed its own downregulation caused by miR-135b mimics. Meanwhile, overexpression of FoxO1 abolished the inhibitory effects of miR-135b on pyroptosis and reversed the downregulation of pyroptotic genes and LDH release. In summary, miR-135b played a protective role in Parkinson's disease via inhibiting pyroptosis by targeting FoxO1. MiR-135b might serve as a potential therapeutic target in the treatment of Parkinson's disease.


Forkhead Box Protein O1/metabolism , Inflammasomes/metabolism , MicroRNAs/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Parkinson Disease/genetics , Pyroptosis/genetics , Carrier Proteins/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Neoplasm Proteins/genetics , Phosphate-Binding Proteins , Up-Regulation
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