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Alloying is an effective strategy to tailor microstructure and mechanical properties of metallic materials to overcome the strength-ductility trade-off dilemma. In this work, we combined a novel alloy design principle, i.e. harvesting pronounced solid solution hardening (SSH) based on the misfit volumes engineering, and simultaneously, architecting the ductile matrix based on the valence electron concentrations (VEC) criterion, to fulfill an excellent strength-ductility synergy for the newly emerging high/medium-entropy alloys (HEAs/MEAs). Based on this strategy, Al/Ta co-doping within NiCoCr MEA leads to an efficient synthetic approach, that is minor Al/Ta co-doping not only renders significantly enhanced strength with notable SSH effect and ultrahigh strain-hardening capability, but also sharply refines grains and induces abnormal twinning behaviors of (NiCoCr)92Al6Ta2 MEA. Compared with the partially twinned NiCoCr MEA, the yield strength (σy) and ultimate tensile strength (σUTS) of fully twinned Al/Ta-containing MEA were increased by ∼102 % to ∼600 MPa and ∼35 % to ∼1000 MPa, respectively, along with good ductility beyond 50 %. Different from the NiCoCr MEA with deformation twins (DTs)/stacking faults (SFs) dominated plasticity, the extraordinary strain-hardening capability of the solute-hardened (NiCoCr)92Al6Ta2 MEA, deactivated deformation twinning, originates from the high density of dislocation walls, micro-bands and abundance of SFs. The abnormal twinning behaviors, i.e., prevalence of annealing twins (ATs) but absence of DTs in (NiCoCr)92Al6Ta2 MEA, are explained in terms of the relaxation of grain boundaries (for ATs) and the twinning mechanism transition (for DTs), respectively.

Jie Liang,1 Huihui Zhang,1 Yue Huang,1 Lilv Fan,1 Fanlin Li,1 Min Li,1 Yaping Yan,1 Junshi Zhang,1 Zeyu Li,1 Xuanming Yang1,2 1Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of ChinaCorrespondence: Xuanming YangSheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of ChinaTel +86-21-34204065Email xuanmingyang@sjtu.edu.cnBackground: Co-stimulatory receptor agonist antibodies have shown promising antitumor efficacy in preclinical models. However, their clinical development lags due to systemic or local adverse effects of non-specific T cell activation. Utilization of a bispecific antibody format to reduce off-tumor immune activation is a focus of co-stimulatory receptor agonist antibody design.Methods: In this study, a bispecific antibody with anti-CLDN18.2 and anti-CD28 moieties was produced. Its T cell costimulation ability was evaluated in T cell coculture assay in vitro. Its safety and anti-tumor efficacy were explored in mouse tumor models.Results: Anti-CLDN18.2-anti-CD28 bispecific antibody could co-stimulate T cells and increase the expression of effector cytokines in a CLDN18.2-dependent manner. Treatment of anti-CLDN18.2-anti-CD28 could reduce tumor burden and increase tumor-infiltrated T cells. Immunosuppressive cells including tumor-associated macrophages and myeloid-derived suppressor cells were also reduced without systemic adverse effects.Conclusion: This work provided proof-of-concept evidence for a new strategy to develop a bispecific co-stimulatory activator for treating CLDN18.2+ tumors.Keywords: CLDN18.2, CD28, bispecific antibody, cancer immunotherapy

Gene therapy is a revolutionary biomedical technique for the treatment of many diseases, and the development of safe and efficient intracellular gene delivery vectors is crucial for successful gene...

Dielectric elastomer sensors (DESs) have demonstrated great potential applications in the fields of human motion capture, rehabilitation training, health monitoring, and soft robotic sensing. However, precise dynamic sensing by DES has not yet been achieved because of the lack of analysis of their dynamic characteristics. This letter analyzes the dynamic characteristics of DESs and finds a remarkable strain delay in dynamic stretching and recovery, which is correlated to historical stretching, deformation speed, and maximum strain. A Burgers four-element model was used to quantitatively analyze the strain delay, and the results are validated by experiment. Strain delay can reduce DES precision, and therefore, a method based on prestretching was proposed to eliminate its influence. Precision of the DES can be remarkably improved after elimination of the strain delay.

How to design ultra-strong, light-weight Cu alloys is a long-term pursuit in materials community, which is technically superior and cost-effective for their promising energy-saving applications. In this work, we prepared Cu-Mg alloyed thin films to study light element Mg alloying effects on the microstructure, hardness and strain rate sensitivity (SRS) of nanocrystalline Cu thin films. In the studied Mg concentration-range spanning from 0 at.% to 16.8 at.%, both the grain size and the twin spacing decrease monotonously with increasing Mg composition while Cu-2.8 at.% Mg sample has the highest twin fraction of ∼75%. A combined strengthening model was employed to quantify the Mg concentration-dependent hardness of nanotwinned (NT) Cu-Mg thin films, in which the grain/twin boundary facilitates strengthening while the solute Mg atoms induce softening. Both the constant rate of loading tests and the nanoindentation creep tests uncover that compared with pure Cu samples, the NT Cu-Mg thin films manifest much lower SRS, particularly in the creep tests, owing to the activation of dynamic strain aging effects.

Interferon (IFN)‐inducible 44 like (IFI44L) is an IFN‐stimulated gene, the expression of which is induced by IFN and human immunodeficiency virus (HIV)‐1 infection. However, the mechanism has not yet been determined. In this study, we cloned the promoter of the IFI44L gene and found that interferon regulatory factor‐1 could bind directly to the IFN‐stimulated response element in the IFI44L promoter to activate IFI44L. Furthermore, we demonstrated that HIV‐1 can activate the IFI44L promoter to influence the expression of IFI44L., Interferon (IFN)‐inducible 44 like (IFI44L) is an IFN‐stimulated gene (ISG), which is located on the same chromosome as the known antiviral ISG IFI44. Expression of IFI44L is induced by IFN and HIV‐1 infection. However, the mechanism by which IFN‐I induces IFI44L production has not yet been determined. In this study, we analyzed transcriptional regulation of IFI44L via cloning of the IFI44L promoter. We found that IFI44L has two IFN‐stimulated response elements (ISRE), which are necessary for the basal level of IFI44L transcription. IFN‐I and IFN‐II can activate the IFI44L promoter through one of the two ISREs. IFN regulatory factor (IRF)‐1 can activate transcription of IFI44L by binding to one of the ISREs. Additionally, co‐transfection of the IFI44L promoter with an HIV‐1 infectious clone or HIV‐1 infection activated IFI44L promoter transcription, but did not upregulate IFI44L expression via ISREs. These findings will help to understand the interaction between IFI44L and HIV‐1, and aid in elucidation of the role of IFI44L in the antiviral innate immune response.

We demonstrate a strategy to stabilize nanoprecipitates in Al–Cu alloys, based on computational design that identifies synergistic solutes (Sc and Fe) that simultaneously segregate to the θ′-Al2Cu/Al interface and strongly bond to one another. Furthermore, Sc and Fe are predicted to each segregate into a separate atomic plane, forming a sandwiched structure reinforcing the interface. This interfacial architecture was realized through a simple heat treatment in a Sc–Fe–Si triple-microalloyed Al–Cu model alloy. Such a back-to-back layered interface, thermodynamically stable and kinetically robust, is found to suffocate nanoprecipitate coarsening at 300°C, enabling a dramatic reduction in creep rate. IMPACT STATEMENT The segregant architecture of synergistic solute at θ′-Al2Cu/Al interface was guided by computational calculations and artificially realized at atomic scale to achieve an ultra-high thermal stability of θ′-Al2Cu, leading to a high creep resistance at 300°C.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Long non-coding RNAs have important regulatory values in various human diseases. Non-coding RNA Activated by DNA Damage (NORAD) was reported to regulate PD progression in vitro, but its functional mechanism is fully unknown. We used 1-methyl-4-phenylpyridinium (MPP+ ) to establish the cell-based PD model. NORAD, microRNA-204-5p (miR-204-5p), and solute carrier family 5 member 3 (SLC5A3) levels were quantified using the quantitative real-time polymerase chain reaction. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry, respectively. The protein levels were analyzed via western blot. Cytotoxicity was assessed by the released lactate dehydrogenase level in cell supernatant. Oxidative stress and inflammation were measured by the standard indicators. Dual-luciferase reporter and RNA immunoprecipitation assays were performed for intergenic combination. First, we found that NORAD was obviously reduced in MPP+ -treated neuroblastoma cells and lightened the MPP+ -induced cytotoxicity, oxidative stress, and inflammatory response. Then, NORAD was shown to be a miR-204-5p sponge and avoided the injury induced by MPP+ in neuroblastoma cells via targeting miR-204-5p. SLC5A3 was a miR-204-5p target and could be regulated by NORAD/miR-204-5p axis. SLC5A3 knockdown assuaged the anti-miR-204-5p-induced protection for neuroblastoma cells from MPP+ . Altogether, NORAD played a neuroprotective role against the progression of MPP+ -induced PD model in neuroblastoma cells relying on the miR-204-5p/SLC5A3 axis. This study afforded the clear elaboration on the PD pathomechanism concerning NORAD.

An AC voltage induces a nonlinear vibration of dielectric elastomers (DEs), which enables DE to be served as soft dynamical devices and robots. As is known, a special beating vibration may occur during the nonlinear oscillation of DEs, leading to the undesired electromechanical failures and instabilities. In this article, a numerical study is developed to explore the beating vibration of DEs with establishment of the dynamics model. The effects of geometric sizes, limiting stretch, as well as amplitude and frequency of applied voltage on the beating vibration performance of DEs are investigated, respectively. The corresponding range of actuation and materials parameters that determines the occurrence of beating vibration is obtained. The phase paths and Poincare maps are employed to detect the stability and periodicity of nonlinear beating vibration of DEs. The bifurcation analyses of dynamic electromechanical performances of DE are also investigated.

It is generally considered that the Al3Sc nanoprecipitates are highly thermal stable, mainly due to quite slow Sc diffusion in the α-Al matrix. In this paper, we demonstrate in an Al-Cu-Sc alloy that the Cu atoms have dual effect on the coarsening of Al3Sc nanoprecipitates. On the one hand, the Cu atoms with high diffusivity tend to accelerate the Al3Sc coarsening, which results from the Cu-promoted Sc diffusion. On the other hand, some Cu atoms will segregate at the Al3Sc/matrix interface, which further stabilizes the Al3Sc nanoprecipitates by reducing the interfacial energy. Competition between these two effects is tailored by temperature, which rationalizes the experimental findings that the coarsening kinetics of Al3Sc nanoprecipitate is greatly boosted at 300 °C-overaging while significantly suppressed at 400 °C-overaging.

Smart hydrogels with good flexibility and biocompatibility have been widely used. The common near-infrared (NIR) photothermal agents are facing a trade-off between good photothermal-conversion efficiency and high biocompatibility. Therefore, developing new metal-free photothermal agents with low cost, high biocompatibility and excellent phase stability is still in urgent need. In this study, we successfully combined poly(N-isopropylacrylamide) (PNIPAM) with the two-dimensional (2D) silicene nanosheets via the in situ polymerization method. Attributed to the thermal-responsive nature of PNIPAM and the excellent photothermal properties of 2D silicene, the obtained silicene/PNIPAM composite hydrogels exhibited dual thermal and NIR responsive properties. This smart hydrogel showed rapid, reversible and repeatable NIR light-responsive behaviors. The volume of this smart hydrogels can shrink significantly under NIR irradiation and recover to its original size without the NIR irradiation. Remote near-infrared light-controlled microfluidic pipelines and electronic switches based on obtained silicene/PNIPAM composite hydrogels were also demonstrated. This work significantly broadens the application prospects of silicene-based hydrogels in remote light-controlled devices.

As is known, the internal material parameters of dielectric elastomers (DEs) may largely affect the corresponding electromechanical performances. In this article, the dynamic stability analysis of viscoelastic DEs with different material parameters is investigated by using the continuous method. Several affecting material parameters, including the geometrical size, viscous damping, limiting stretch, and shear modulus, are considered, respectively. Continuous variation of geometrical size is found to induce the dynamic instability of DE, while the viscous damping and limiting stretch have limited connection with the occurrence of dynamic instability. Furthermore, increase in the ratio of the shear modulus also causes the dramatic jump of dynamic deformation of DE membranes.

Zr/Mo and Zr/Ti nanostructured multilayers manifest a peak hardness at the critical layer thickness of ~10 and ~20 nm, respectively. The non-monotonical thickness-dependent hardness is understood in terms of the back stress, which is closely correlated with the dislocation absorption probability by the interfaces. It appears that strength softening occurs as gliding dislocations can be absorbed by interfaces at smaller layer thickness. Furthermore, incoherent interface in the Zr/Mo with discontinuous slip systems is more effective to block dislocation motion than the Zr/Ti with continuous ones, resulting in a higher dislocation storage ability.

In order to quantify the fracture toughness and reveal the failure mechanism of crystalline/amorphous nanolaminates (C/ANLs), in-situ micro-cantilever bending tests were performed on Ag/Cu–Zr and Mo/Cu–Zr C/ANLs in a scanning electron microscope over a wide range of cantilever widths from several microns to the submicron scale. The results demonstrate that the fracture behavior was strongly influenced by sample size and constituent phases, respectively. The Ag/Cu–Zr micro-cantilevers failed in a ductile manner, with fracture toughnesses higher than the Mo/Cu–Zr samples that exhibited brittle failure. Both materials also displayed different cantilever width-dependences of fracture toughness. The Ag/Cu–Zr beams showed a fracture toughness that increases with the cantilever width, mainly due to a size-dependent constraining effect on the deformation of the crystalline phase. For the Mo/Cu–Zr beams, the fracture toughness decreased gradually to a low plateau as the cantilever width exceeded ∼1500 nm, which can be rationalized by a transition in stress condition. The underlying fracture mechanism of the Ag/Cu–Zr micro-cantilevers was identified as the interconnection of microcracks initiated in the amorphous Cu–Zr layers, compared to a catastrophically penetrating crack propagation in the Mo/Cu–Zr samples. The discrepancy in size-dependent fracture behavior between the two material systems is discussed in terms of plastic energy dissipation of ductile phases, crack tip blunting, crack bridging and the effect of strain gradient in the plastic zone on crack propagation.

Nanostructured crystalline Al/amorphous AlN multilayer films with a wide layer thickness (h) range from ∼10 nm up to ∼200 nm were prepared by using magnetron sputtering. Nanotwins and 9R phase were substantially observed in the Al layers, showing a strong thickness dependence. The 9R phase predominantly penetrated through the Al layer in the II regime of h ≤ ∼20 nm, while mainly terminated within the layer interior in the I regime of h > ∼20 nm. On the contrary, the coherent nanotwins were boosted when h > ∼20 nm and the percentage of twinned Al grains was greatly increased. The formation mechanisms of 9R phase and coherent nanotwins were discussed in terms of the interfacial chemistry/physics modulated by the amorphous AlN layers, which displayed gradient characteristics and hence was sensitive to the layer thickness. A significant thickness dependence of hardness was also evident that the hardness monotonically increased with reducing h in the I regime, while reached a peak value and hold almost unchanged in the II regime. The hardness in the II regime is about 1 GPa greater than the predictions from an interfacial barrier crossing model. This discrepancy is mainly contributed by the layer-penetrating 9R phase rather than the nanotwins. This study provides a new perspective on fabricating nanotwinned Al by utilizing heterophase interfaces.

BACKGROUND This study aimed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphisms with left ventricular hypertrophy (LVH) in Han and Uighur hypertension-OSAHS (obstructive sleep apnea hypopnea syndrome) patients in China. MATERIAL AND METHODS A total of 162 Han and 72 Uygur patients with hypertension-OSAHS were independently subdivided into an LVH group and a non-LVH (NLVH) group based on the left ventricular mass index. The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction. The association of ACE gene insertion/deletion polymorphisms with LVH was assessed by chi-squared test. Logistic regression analysis was performed to obtain the odds ratios and 95% confidence intervals for the risk of LVH after adjusting for confounding factors. RESULTS In Uighur patients, the distributions of D allele and DD genotype showed significant differences between the LVH group and the NLVH group. The difference of DD genotype remained significant after multivariate adjustment. In contrast, no significant differences were observed in the distributions of D allele and DD genotype between the LVH group and the NLVH group in Han patients. Moreover, moderate-severe OSAHS was an independent risk factor for LVH. CONCLUSIONS D allele and DD genotype of ACE gene are possible genetic markers for the risk of LVH in Uighur but not Han hypertension-OSAHS patients.

The fragmentation and interfacial stress transfer of Cu75Zr25 amorphous films with varying film thickness (h) on polyimide substrates were systematically investigated by using uniaxial tensile testing, in combination with in situ optical microscope and atomic force microscope characterizations. It is revealed that the interfacial stress transfer length increases monotonically as h increases. The interfacial stress transfer mechanism changes from elastic-plastic to approximately linear elastic at a critical point of h = 250 nm. This is related to h-dependent deformation-induced devitrification (DID) near the interfaces that the thinner Cu-Zr amorphous films display more DID. This study elucidates for the first time the effect of DID on the interfacial stress transfer, which will be helpful to design the interface with desired property for nanotechnological applications.

This study reveals two-stage wrinkling behavior of Al films deposited on polydimethylsiloxane (PDMS) substrates by magnetron sputtering at a high temperature. The hierarchical structures with nano-micro dual scale wrinkles were created in Al films. The micro-scale wrinkles originated from thermal contraction, with the wavelength increasing with increasing film thickness, while nano-scale wrinkles, with an almost unchanged wavelength, are induced by the expansion of the mixed layer on the PDMS surface. The results provide a facile method to produce the hierarchical wrinkled surfaces for functionality.

We report the formation of wrinkles with tunable wavelength in Ag films and Mo films deposited on polydimethylsiloxane (PDMS) and PDMS/Si substrates by magnetron sputtering at 50 °C. The PDMS-supported Ag films have the wrinkles with μm-sized wavelength, while the sub-μm-sized wrinkles are engendered in the Ag films on PDMS/Si substrates due to the constraint from the substrates. By contrary, Mo films with a similar thickness range exhibit wrinkles with μm-sized wavelength on the PDMS/Si substrates, much larger than that of Ag films on the same substrates. This indicates that the wrinkle wavelength in metal films depends closely on the substrates and the characteristics of metal films. The possible reasons for the discrepancy in wavelength between experiments and theoretical predictions are discussed. The wettability of the wrinkled surfaces is predominantly controlled by the length scale of the wrinkles. In the Ag films with sub-μm-sized wrinkles, droplet contact angle is highly sensitive to the surface roughness, i.e., increasing quickly with the surface roughness. However, in the PDMS-supported Ag and PDMS/Si-supported Mo films both with μm-sized wrinkles, the contact angle raises slowly with the surface roughness. It is thus evident that a wettability spectrum derived from the wrinkling pattern can be artificially developed by tuning the wavelength in different length scales through controlling of substrates, metal films, and film thicknesses.

The mechanical behavior of (Fe40Mn40Co10Cr10)100−xCx (x = 0, 2.2, 3.3 at.%) high entropy alloys (HEA) at various temperatures (298 K, 159 K and 77 K) was investigated. For Fe40Mn40Co10Cr10 HEA, the jointly activated twinning and martensitic phase transformation concurrently increase the strength and ductility at 77 K. In contrast, twinning and phase transformation gradually vanish as temperature decreases for carbon alloyed HEAs, resulting in ductile-brittle transition. Our findings indicate that the additional interstitial carbon atoms increase the f.c.c. phase stability, and inhibit the deformability of Fe40Mn40Co10Cr10 HEA at low temperature.

The buckling and post-buckling behavior of the Cu–Zr amorphous films is highly dependent on film thickness (h) and applied strain (e). A buckling map has been developed with h and e as axes, where four buckling modes are detected, including uncracked triangular buckle, cracked rectangular buckle, cracked triangular buckle, and patches. Formation of the four buckling modes will be discussed in terms of the film thickness and size-dependent deformation.

In this work, cohesive and adhesive properties of Ti thin films on polyimide substrates were studied systematically as a function of grain size by in situ optical microscopy, resistance measurements and synchrotron X-ray diffraction under uniaxial tensile testing. The characteristic of cohesive and adhesive behavior can be well reflected in the stress-strain curves determined by synchrotron X-ray diffraction. Generally, the yield strength decreases while the cracking strain increases with increasing grain size, due to the constraint effect of grain size on dislocation activity. Different from the yield strength, the fracture strength is almost unchanged with grain size. The fracture toughness is found to increase as the grain size increases, which is attributed to the enhanced plasticity during fracture process. Additionally, the interfacial adhesion energy is determined to be 3.8 J m−2. The buckling strain increases with increasing grain size as a result of enhanced plastic dissipation. The formation of patches, instead of buckles, in Ti film with smaller grain size is ascribed to the low deformation capability of the film.

Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration.SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment.This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population.Chinese Clinical Trials Register ChiCTR2200061938.

The Fos proto‑oncogene, activator protein‑1 (AP‑1) transcription factor subunit (c‑fos) gene, a member of the immediate early gene family, encodes c‑Fos, which is a subunit of the AP‑1 transcription factor. The present study aimed to investigate the mechanism by which the translation efficiency of c‑fos mRNA is upregulated when cellular protein synthesis is shut off. The result of western blotting revealed that the protein expression levels of c‑Fos were increased in rhabdomyosarcoma cells infected with enterovirus 71 (EV71) compared with uninfected cells. PCR was used to get the c‑fos 5'‑untranslated region (UTR). The luciferase assay of a bicistronic vector containing the c‑fos 5'UTR revealed that the c‑fos 5'UTR contains an internal ribosome entry site (IRES) sequence and a 175 nucleotide sequence (between 31 and 205 nt) that is essential for IRES activity. Analysis of potential IRES trans‑acting factors revealed that poly(C)‑binding protein 2 (PCBP2) negatively regulated the activity of the c‑fos IRES, whereas the La autoantigen (La) positively regulated its activity. The results of RNA‑protein immunoprecipitation demonstrated that both PCBP2 and La bound to the c‑fos 5'UTR. Furthermore, the IRES activity of in vitro‑transcribed c‑fos mRNA was upregulated during EV71 infection. The present study suggested a mechanism for the effect of viral infection on host genes, and provided a novel target for gene translation regulation.

Membrane proteins of enveloped viruses have been reported to undergo palmitoylation, a post-translational modification often having a critical role in the function of these viral proteins and hence viral replication. In this study, we report that the foamy virus (FV) envelope (Env) glycoprotein is palmitoylated. Specifically, we found that bovine foamy virus (BFV) Env (BEnv) is palmitoylated at amino acid positions C58 and C59 by BDHHC3 and BDHHC20 in a DHHC motif-dependent manner. In addition, mutations C58S and C58/59S significantly decrease cell surface expression of BEnv, subviral particle (SVP) egress, and its membrane fusion activity, thus ultimately inhibiting BFV replication. The C59S mutation exerts a minor effect in this regard. Taken together, these data demonstrate that the function of BEnv in the context of BFV replication is under the regulation of palmitoylation.

The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their vascular endothelial growth factor-A (VEGFA) protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was down-regulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3′UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.

Background Parkinson's disease (PD) is the second most common neurodegenerative disease. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) has been demonstrated as an important regulator in PD pathology. However, the functional mechanisms played by SNHG14 in PD remain largely unclear. Methods We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) to establish PD mouse and cell models. The levels of SNHG14, miR-214-3p, and Kruppel-like factor 4 (KLF4) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Cell viability and apoptosis were determined using the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of inflammatory cytokines were evaluated by ELISA. The relationships among SNHG14, miR-214-3p, and KLF4 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results Our data indicated that SNHG14 was upregulated and miR-214-3p was downregulated in PD models. SNHG14 knockdown ameliorated MPP+-stimulated damage in SK-N-SH cells, as evidenced by the enhancement in cell viability and the suppression in cell apoptosis and pro-inflammatory cytokine production. Mechanistically, SNHG14 directly targeted miR-214-3p via binding to miR-214-3p, and SNHG14 knockdown protected SK-N-SH cell from MPP+-stimulated cytotoxicity by upregulating miR-214-3p. KLF4 was a direct target of miR-214-3p, and SNHG14 regulated KLF4 expression by acting as a miR-214-3p sponge. Furthermore, miR-214-3p overexpression alleviated MPP+-stimulated damage in SK-N-SH cells by downregulating KLF4. Conclusion Our current study first demonstrated the protective effect of SNHG14 knockdown on MPP+-stimulated cytotoxicity in SK-N-SH cells at least partially by targeting the miR-214-3p/KLF4 axis, illuminating a promising target for PD intervention and treatment.