Search

Background: The cardiac resynchronization therapy (CRT) non‐response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. Methods: Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non‐response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF) < 5% at a 6‐month follow‐up. Results: A total of 132 patients (mean age 63.0 ± 10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (‐) group. The CRT non‐response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (‐) group (68.8% vs. 33.3%, p <.001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non‐response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5–15.0, p =.007). Conclusion: Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non‐response in patients with HF and LBBB. [ABSTRACT FROM AUTHOR]

Inorganic modified green mudstone (MGM) was prepared from the green mudstone (GM) residue of Fushun West Open Pit Mine and characterized by XRF, XRD, FTIR, and SEM of GM and MGM. According to the calculation of pore size and the BET equation, the pore size and specific surface area of the MGM were larger. The results of adsorption kinetics and isothermal adsorption experiments showed that the adsorption capacity of MGM for phosphate increased from 0.1 mg/g to 0.71 mg/g, which was obviously better than that of GM. The GM and MGM accorded with the quasi-second-order kinetic model. The isothermal adsorption data of GM accorded with the Freundlich model, and the isothermal data of MGM accorded with the Langmuir model, which indicated that the model of GM and MGM was an adsorption process from a double layer to a single layer. Thermodynamic data showed that the increase in temperature was beneficial to the adsorption of MGM. The internal diffusion model showed that due to the change of pore size structure after modification, the number of adsorption sites that could provide phosphate was increased, and at the same time, the change of internal elements led to the extension of the chemical reaction time by 700 min. Because of the ligand exchange and electrostatic interaction between phosphate, GM, and MGM, the adsorption results showed that acidity was better than alkalinity. To improve the recycling ability of MGM, hydrochloric acid with a concentration of 0.1 mol/L was determined as the best phosphorus resolving agent, and the resolving rate was still close to 80% after five cycles. The results showed that the MGM could be a promising adsorbent for the removal of phosphorus, providing a new way for resource utilization of mining waste residue. [ABSTRACT FROM AUTHOR]

Regarding the complex properties of various cations, the design of aqueous batteries that can simultaneously store multi‐ions with high capacity and satisfactory rate performance is a great challenge. Here an amorphization strategy to boost cation‐ion storage capacities of anode materials is reported. In monovalent (H+, Li+, K+), divalent (Mg2+, Ca2+, Zn2+) and even trivalent (Al3+) aqueous electrolytes, the capacity of the resulting amorphous MoOx is more than quadruple than that of crystalline MoOx and exceeds those of other reported multiple‐ion storage materials. Both experimental and theoretical calculations reveal the generation of ample active sites and isotropic ions in the amorphous phase, which accelerates cation migration within the electrode bulk. Amorphous MoOx can be coupled with multi‐ion storage cathodes to realize electrochemical energy storage devices with different carriers, promising high energy and power densities. The power density exceeded 15000 W kg−1, demonstrating the great potential of amorphous MoOx in advanced aqueous batteries. [ABSTRACT FROM AUTHOR]

A robust ionospheric model is indispensable for providing the atmospheric delay corrections for global navigation satellite system (GNSS) navigation and positioning and forecasting the space environment. The accuracy of ionospheric models is limited due to the simplified model structures. Complicated spatiotemporal variations in total electron content (TEC) biases between GNSS and international reference ionosphere (IRI) suggest a robust strategy to optimally combine GNSS and IRI TEC for high-precision modeling. In this paper, we propose a novel ionospheric data assimilation method, which is a local ensemble transform Kalman filter (LETKF), to construct an ionospheric model over Yunnan in southwestern China. We used the LETKF method to assimilate the ionospheric TEC extracted from GNSS observations in Yunnan into the IRI-2016 model. The experimental results indicate that the ionospheric data assimilation has a more pronounced improvement effect on the IRI empirical model during periods of geomagnetic quiet than during periods of geomagnetic disturbance. On quiet magnetic days, the skill score (SKS) of the assimilation is 0.60 and the root mean square error (RMSE) values before and after assimilation are 5.08 TECU and 2.02 TECU, respectively. The correlation coefficient after assimilation increases from 0.94 to 0.99. On magnetic storm days, the SKS of the assimilation is 0.42 and the RMSE values before and after assimilation are 5.99 TECU and 3.46 TECU, respectively. The correlation coefficient after assimilation increases from 0.98 to 0.99. The results suggest that the LETKF algorithm can be considered an effective method for ionospheric data assimilation. [ABSTRACT FROM AUTHOR]

Altered abundance or activity of the dual-function transient receptor potential melastatin-like 7 (TRPM7) protein is implicated in neurodegenerative disorders, including Alzheimer's disease (AD). Toxic aggregation of amyloid-β (Aβ) in neurons is implicated in AD pathology. Here, we found that the kinase activity of TRPM7 is important to stimulate the degradation of Aβ. TRPM7 expression was decreased in hippocampal tissue samples from patients with AD and two mouse models of AD (APP/PS1 and 5XFAD). In cultures of hippocampal neurons from mice, overexpression of full-length TRPM7 or of its functional kinase domain M7CK prevented synapse loss induced by exogenous Aβ. In contrast, this neuroprotection was not afforded by overexpression of either the functional ion channel portion alone or a TRPM7 mutant lacking kinase activity. M7CK overexpression in the hippocampus of young and old 5XFAD mice prevented and reversed, respectively, memory deficits, synapse loss, and Aβ plaque accumulation. In both neurons and mice, M7CK interacted with and activated the metalloprotease MMP14 to promote Aβ degradation. Thus, TRPM7 loss in patients with AD may contribute to the associated Aβ pathology. Editor's summary: The abundance of the dual-function ion channel and kinase TRPM7 is decreased in postmortem brain samples from patients with Alzheimer's disease (AD). Zhang et al. uncovered a pathological role for loss of TRPM7 in AD. In mice modeling amyloid-β–induced pathology, synapse formation and cognitive function were restored in aged mice and preserved in pre-symptomatic, younger mice upon overexpression of the kinase portion of TRPM7 (called M7CK). M7CK directly activated the protease MMP14, which promoted amyloid-β degradation and clearance. The findings may provide a mechanistic link between TRPM7 loss and amyloid pathology in AD patients.–Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

Aqueous zinc-ion batteries (ZIBs) have attracted increasing attention due to their low cost and high safety. MoS2 is a promising cathode material for aqueous ZIBs due to its favorable Zn2+ accommodation ability. However, the structural strain and large volume changes during intercalation/deintercalation lead to exfoliation of active materials from substrate and cause irreversible capacity fading. In this work, a highly stable cathode was developed by designing a hierarchical carbon nanosheet-confined defective MoSx material (CNS@MoSx). This cathode material exhibits an excellent cycling stability with high capacity retention of 88.3% and ∼ 100% Coulombic efficiency after 400 cycles at 1.2 A·g−1, much superior compared to bare MoS2. Density functional theory (DFT) calculations combined with experiments illustrate that the promising electrochemical properties of CNS@MoSx are due to the unique porous conductive structure of CNS with abundant active sites to anchor MoSx via strong chemical bonding, enabling MoSx to be firmly confined on the substrate. Moreover, this unique hierarchical complex structure ensures the fast migration of Zn2+ within MoSx interlayer. [ABSTRACT FROM AUTHOR]

Aqueous zinc‐ion battery is one of the candidates for the next generation batteries due to its reliable safety, environmental friendliness and low cost. While the poor structurally stability and limited cyclic reversibility of the cathode restricts its practical application. In this work, we elaborately design hierarchical three‐dimensional (3D) carbon networks (CNs) for the embedding of non‐stoichiometry MnOx with abundant defects (MnOx/CNs), which provide 3D diffusion pathway and efficient electrochemical active sites for zinc‐ion storage. The as‐designed Zn//MnOx/CNs battery delivers high energy density of 452.2 Wh kg−1 at a power density of 133.0 W kg−1, much superior to that of MnO2/CNs and pristine MnO2. Moreover, defective manganese species experience stable phase transformation during charging/discharging process, providing a long‐term cycling performance with a high reversible capacity of 263.3 mAh g−1 at 1 A g−1 after 1000 cycles. [ABSTRACT FROM AUTHOR]

Simple Summary: Spodoptera litura is an important agricultural pest widely distributed around the world, which can damage numerous crops. Despite its economic importance, research on the population genetics of S. litura has been limited, preventing insight into the spread of the pest. In this study, we conducted a population genetic analysis of 24 populations of S. litura in Southern China using microsatellite markers, demonstrating the information on the genetic diversity and genetic structure of the tested populations. The results will provide pest control management strategies for S. litura in Southern China. Population genetic structure is strongly affected by dispersal events, especially for migratory species. The investigation of population structure is therefore conducive to increasing our understanding of species dispersal. Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is an important tobacco pest in China causing serious damage to multiple crops. In this study, we explore its dispersal dynamics by clarifying the fine-scale population genetics using 545 S. litura samples collected from tobacco plantations at 24 locations (mainly in Baise, Hechi, and Hezhou, Southern China). We analyzed the genetic diversity, genetic structure, and gene flow of these populations using seven microsatellite loci. Our results revealed high genetic diversity and low population genetic structure among S. litura. The genetic distance was uncorrelated with geographical distance, indicating the complete randomness of dispersal among the local populations. Our results suggest that the movement scope of contemporary S. litura might be much higher than the local-level spatial scale, which will provide a theoretical basis for pest management. [ABSTRACT FROM AUTHOR]

Near-infrared emitting nano-sized particles of ZnGa2−x(Mg/Si)xO4:Cr3+ (x = 0–0.15, termed as ZGMSO:Cr3+) with persistent luminescence were prepared by sol-gel processing followed by calcination. The samples were tested by XRD, TEM, STEM, SAED, Raman, XPS, UV-Vis-NIR, TL, PLE/PL spectroscopy, and persistent luminescence decay analysis. Equimolar incorporation of Mg2+ and Si4+ ions did not change the spindle structure of ZnGa2O4 seriously. Most Mg2+ ions are more likely to occupy the sites in octahedron, but Si4+ ions are more likely to occupy the sites in tetrahedron in priority. A broader bandgap, up shift of conduction band minimum, and more anti-defects were found at a higher Mg2+/Si4+ doping concentration. ZGMSO:Cr3+ outputs near-infrared emission with a dominated band at 694 nm (2E → 4A2 transition of Cr3+), which can last longer than 48 h after the stoppage of UV irradiation. Mg2+/Si4+ doping contributes to a better near-infrared persistent luminescence, and the strongest and the longest NIR afterglow was observed at x = 0.05, owing to that the x = 0.05 sample has the deepest defects. The synthesized nanoparticles of ZGMSO:Cr3+ not only output intense NIR afterglow but also can be recharged by the red light of LED several times, indicating that they are the potential nano probes for bio imaging in living animals. [ABSTRACT FROM AUTHOR]

China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥ 65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1± 5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China. [ABSTRACT FROM AUTHOR]

Ionospheric total electron content (TEC) is important data for ionospheric morphology, and also an important parameter for ionospheric correction in Global Navigation Satellite System (GNSS) precise positioning, navigation, and radio science. In this study, we present a data assimilation model for regional ionosphere based on a local ensemble Kalman filter (LEnKF) with the International Reference Ionosphere 2016 (IRI-2016) model as the background, to assimilate ionospheric TEC observations from GNSS. To demonstrate the results, the TEC estimates from the Crustal Movement Observation Network of China (CMONOC), which is about 260 stations in China, are applied as observation. The assessments are performed against the TEC estimates from BeiDou Navigation Satellite System (BDS) geostationary earth orbit (GEO) and against the final products from the Center for Orbit Determination in Europe (CODE). The assimilation results are in good agreement with BDS GEO TEC and the CODE TEC on a quiet or disturbed day. The correlation coefficient after assimilation is increased by about 17% compared with that before assimilation, and the RMSE after assimilation is decreased by about 42% compared with that before assimilation. Furthermore, the assimilated method is also evaluated in the single-frequency precise point positioning (PPP). The experimental results indicate that the PPP/Assimilated method can improve the GNSS positioning accuracy more effectively in comparison to the PPP/CODE. These results reveal that the LEnKF method can be considered as a useful tool for ionospheric assimilation. [ABSTRACT FROM AUTHOR]

Lithium–sulfur batteries (Li–S) have been gradually becoming one of the most promising next-generation storage systems, but their practical application is still limited by the extremely low S loading as well as the poor rate capability. Herein, Li–S batteries with boosting rate performance under high mass-loading of S have been achieved based on the hierarchical NCNT@Co-CoP nanowire integrated electrode. The experiments and density functional theory calculations demonstrate that the Co-CoP heterojunction interface simultaneously improves the ion transportation/electron migration, and efficiently confines and catalyzes the conversion of lithium polysulfides (LiPSs). Moreover, the ex situ scanning electron microscopy image and in situ Raman spectra further demonstrate the obviously reduced volume expansion and efficient catalytic conversion of LiPSs on NCNT@Co-CoP-1 even at a high S loading. As a result, Li–S batteries with the NCNT@Co-CoP cathode deliver superior cyclability and remarkable rate capability with 603.9 mA h g−1 after 900 cycles at 5C. Moreover, a high areal capacity retention of 4.4 mA h cm−2 after 100 cycles at 2C rate can also be achieved even under higher loading (10 mg cm−2) and low E/S ratio (7 μL mg−1), illustrating its great practical application in high-rate performance Li–S batteries. [ABSTRACT FROM AUTHOR]

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization. In the steady state, Tsc1 in T cells intrinsically suppresses spontaneous GC-Tfh cell differentiation and subsequent GC-B cell formation and autoantibody production. In immune responses to antigen immunization, Tsc1 in T cells is required for efficient GC-Tfh cell expansion, GC-B cell induction, and antigen-specific antibody responses, at least in part via promoting GC-Tfh cell mitochondrial integrity and survival. Interestingly, in mixed bone marrow chimeric mice reconstituted with both wild-type and T cell-specific Tsc1-deficient bone marrow cells, Tsc1 deficiency leads to enhanced GC-Tfh cell differentiation of wild-type CD4 T cells and increased accumulation of wild-type T regulatory cells and T follicular regulatory cells. Such bystander GC-Tfh cell differentiation suggests a potential mechanism that could trigger self-reactive GC-Tfh cell/GC responses and autoimmunity via neighboring GC-Tfh cells. [ABSTRACT FROM AUTHOR]

Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)‐mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKζ function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKζ function are still poorly understood. We report here that DGKζ dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKζ mutant defective in nuclear localization displayed enhanced ability to inhibit TCR‐induced DAG‐mediated signaling in primary T cells, maturation of conventional αβT and iNKT cells, and activation of peripheral T cells compared with WT DGKζ. Our study reveals for the first time nuclear sequestration of DGKζ as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKζ nucleus‐cytosol shuttling as a novel strategy to modulate DGKζ activity and immune responses for treatment of autoimmune diseases and cancer. [ABSTRACT FROM AUTHOR]

Zinc‐ion batteries (ZIBs) have attracted considerable attention and global interest due to their high gravimetric and high volumetric capacities (820 mAh g−1 and 5855 mAh cm−3). However, the Zn protrusions/dendrites during the plating/stripping process of Zn (Zn2+) severely affect the performance of Zn anode, causing a low Coulombic efficiency, rapid degradation of capacity, and even failure of Zn‐anode‐based batteries. In order to reduce the dendritic deposition of Zn, the key is to adjust the initial uniform nucleation, which determines the subsequent uniform deposition of Zn. Herein, a cathode material (MnO2) ultrathin film is first modified on the surface of the carbon cloth as active sites for the in situ nucleation and directed epitaxial growth of metal Zn. As a result, the CC@MnO2‐UTF@Zn anode can be cycled in aqueous electrolyte and maintain stable cycling performance during repeated Zn deposition/stripping processes. Subsequently, the CC@MnO2‐UTF@Zn anode and CC@MnO2 cathode are assembled into full cells, which deliver a superior electrochemical performance. Moreover, the flexible solid‐state ZIBs with the CC@MnO2‐UTF@Zn anode show excellent capacities and high energy/power densities, which is superior to the most reported results so far. This work provides a new strategy to design an advanced flexibility Zn anode toward future high‐performance wearable electronic ZIBs. [ABSTRACT FROM AUTHOR]

Mucosal‐associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19‐Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR and their regulation in MAIT cells are unknown. Diacylglycerol (DAG) is a critical second messenger that relays the TCR signal to multiple downstream signaling cascades. DAG is terminated by DAG kinase (DGK)‐mediated phosphorylation and conversion to phosphatidic acid. We have demonstrated here that downregulation of DAG caused by enhanced DGK activity impairs late‐stage MAIT cell maturation in both thymus and spleen. Moreover, deficiency of DGKζ but not DGKα by itself causes modest decreases in MAIT cells, and deficiency of both DGKα and ζ results in severe reductions of MAIT cells in an autonomous manner. Our studies have revealed that DAG signaling is not only critical but also must be tightly regulated by DGKs for MAIT cell development and that both DGKα and, more prominently, DGKζ contribute to the overall DGK activity for MAIT cell development. [ABSTRACT FROM AUTHOR]

Thripidae, one of the largest families of Thysanoptera, is widely distributed throughout the world. To explore the phylogenetic relationships and current classification of Thripidae, a cladistic analysis is presented based on 117 morphological characters scored from 114 species representing 94 genera. This analysis was used to reconstruct the ancestral feeding habits of Thripidae, with the result that leaf-feeding is recognised as ancestral within this family, and flower-feeding derived. Thripidae is recovered as a monophyletic group, but the three subfamilies Dendrothripinae, Sericothripinae and Panchaetothripinae are all recovered as nested within the fourth and major subfamily Thripinae. Sericothripinae is related to the Scirtothrips genus-group in Thripinae, but a close relationship to Echinothrips is not supported. Intergeneric relationships within Dendrothripinae are relatively well resolved. Three tribes in Panchaetothripinae are not monophyletic but Tryphactothripini genera form a clade with Panchaetothrips. Subfamily Thripinae is paraphyletic, but includes several monophyletic genus-groups (Rhamphothrips genus-group, Trichromothrips genus-group, Thrips genus-group, Frankliniella genus-group, Chirothrips genus-group). Relationships within the Thrips genus-group are poorly resolved, presumably due to a high degree of homoplasy. Five genera (Amomothrips , Moundinothrips , Smilothrips , Ctenothrips and Sciothrips) are placed into the Taeniothrips genus-group, and three genera (Salpingothrips , Tusothrips and Chaetanaphothrips) are proposed as the Chaetanaphothrips genus-group. The previously accepted Anaphothrips genus-group and Mycterothrips genus-group are not recovered, presumably because the supporting characters are merely superficial resemblance with no phylogenetic significance. This work resolves the systematic relationships among most thripid genera, as well as providing a morphological background for the evolution of Thripidae. Thripidae is the second largest family of Thysanoptera, but little emphasis has been placed on phylogenetic relationships among genera. This cladistic analysis based on morphology revealed the monophyly of the subfamilies and several genus-groups, and resolved the systematic relationships among most genera. This work provides a factual background for better understanding the evolution of Thripidae genera, as well as the phylogeny of Thysanoptera. [ABSTRACT FROM AUTHOR]

Scirtothrips , one of the largest genera of Thripinae, includes several species that are important pests for agricultural and horticultural plants. Scirtothrips genus-group comprises 11 genera, but phylogenetic relationships among these are unclear, as are the interspecific relationships within Scirtothrips. We used 61 morphological characters to study the morphological variation and phylogenetic relationships among the members of this genus-group. Phylogenetic analysis supported the inclusion of eight genera in Scirtothrips genus-group but excluded Ajothrips and Scirtidothrips , although the monophyly of Scirtothrips was not well-supported. Our analysis strongly supported two different species-groups both comprising species associated with Acacia in Australia, suggesting the occurrence of at least two separate radiations onto this plant genus. The monophyly of Scirtothrips perseae species-group was not supported; members of this group are involved in damage to avocado in the New World. The Scirtothrips aurantii species-group was recognised as comprising S. aurantii , Scirtothrips dodonaeae and Scirtothrips mugambii , based on one synapomorphic character, male hind femora with a comb of setae. We demonstrated that the conspicuous drepanae that occur in males of some Scirtothrips species evolved separately in New and Old World species. We discussed the relationships among Scirtothrips species together with data on geographic distributions and host plants, and noted inconsistencies that presumably result from homoplasy. [ABSTRACT FROM AUTHOR]

Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world's medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined. Infection of rAd-HGF produced secretory HGF and promoted hBMSC proliferation in a MOI-dependent manner, while the osteogenesis was also strengthened as indicated by enhanced calcium nodule formation with the strongest effects achieved at MOI = 250. Blocking the activities of c-MET or its downstream signaling pathways, WNT, ERK1/2, and PI3K/AKT led to differential consequents. Specifically, blockage of the WNT pathway significantly promoted osteogenic differentiation, which also showed additive effects when combined application with rAd-HGF. Our data demonstrated the pro-osteogenic effects of optimized MOIs of rAd-HGF, while inhibition of WNT pathway or activation of PI3K/AKT pathway may act as candidate adjuvant modalities for promoting osteogenic differentiation in rAd-HGF-modified hBMSC treatment on ANFH. [ABSTRACT FROM AUTHOR]

Arctigenin (ARC), a phenylpropanoid dibenzylbutyrolactone lignan derived from Arctium lappa L, has been reported to protect against cerebral ischemia injury in rats, but the underlying mechanism is unclear. In this study, we investigated whether ARC ameliorated ischemic stroke by inhibiting NLRP3 inflammasome-derived neuroinflammation and whether SIRT1 signaling was involved in this process. ARC (20 mg/kg) or vehicle were intraperitoneally injected to Sprague-Dawley rats for 3 days before middle cerebral artery occlusion (MCAO) surgery performed. The infarct volume, neurological score, brain water content, neuroinflammation, NLRP3 inflammasome activation and SIRT1 protein expression were assessed. Furthermore, we also investigated whether ARC protected against cerebral ischemia via SIRT1-dependent inhibition of NLRP3 inflammasome by administrating EX527, a specific SIRT1 inhibitor, under oxygen–glucose deprivation (OGD) condition. We found that ARC pretreatment decreased infarct volume, neurological score and brain water content. Moreover, ARC treatment effectively inhibited cerebral ischemia induced NLRP3 inflammasome activation and IL-1β, IL-18 secretion both in vivo and in vitro . Futhermore, ARC treatment activated Silent information regulator 1 (SIRT1) singnaling in the brain. Importantly, suppress of SIRT1 reversed the inhibitory effect of ARC on NLRP3 inflammasome activation. Taken together our results demonstrated that ARC may confer protection against ischemic stroke by inhibiting NLRP3 inflammasome activation. The activation of SIRT1 signaling pathway may contribute to the neuroprotection of ARC in MCAO. [ABSTRACT FROM AUTHOR]

Na0.5Bi0.5TiO3 ( NBT) platelets with high aspect ratio were synthesized from Na0.5Bi4.5Ti4O15 ( NBIT) precursors via a topochemical microcrystal conversion in molten salt conditions. The effect of the synthesis parameters, such as the molten salt system, synthesis temperature, and the molar ratio of Na2 CO3 and NBIT, was investigated. The results showed that NaCl- KCl molten salt environment and excess Na2 CO3 played a positive role in the synthesis, square-shaped NBT was obtained at 950°C in NaCl- KCl molten salt and a TiO2-free environment, and it was a suitable template candidate to achieve NBT-based textured ceramics using the reactive template grain growth ( RTGG) method. [ABSTRACT FROM AUTHOR]

Background: Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study.Methods: The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2-GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2-GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA.Results: The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice.Conclusion: These results suggested that IL2-GMCSF can efficiently regulate immune responses against tumors. Furthermore, as the bridging effect relies on both IL-2R and GM-CSFR and promotes interactions between immune and tumor cells, IL2-GMCSF may be utilized as a useful tool for dissecting specific immune responses for future clinical applications. [ABSTRACT FROM AUTHOR]

Background/Aims: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. Methods: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. Results: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-a, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-a, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. Conclusions: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment. [ABSTRACT FROM AUTHOR]

Abstract: HBx, a transcriptional transactivating protein of hepatitis B virus (HBV), is required for viral infection and has been implicated in virus-mediated liver oncogenesis. However, the precise molecular mechanism remains largely elusive. We used the yeast two-hybrid system to identify that HBx interacts with MIF directly. Macrophage migration inhibitory factor (MIF) is implicated in the regulation of inflammation, cell growth, and even tumor formation. The interaction between HBx and MIF was verified with co-immunoprecipitation, GST pull-down, and cellular colocalization. The expression of MIF was up-regulated in HBV particle producing cell 2.2.15 compared with HepG2 cell. Both HBx and MIF cause HepG2 cell G0/G1 phase arrest, proliferation inhibition, and apoptosis. However, MIF can counteract the apoptotic effect of HBx. These results may provide evidence to explain the link between HBV infection and hepatocellular carcinoma. [Copyright &y& Elsevier]

Beclin 1 is a well-established core mammalian autophagy protein. Autophagy has been demonstrated to play roles in cellular responses to DNA damage, such as cell cycle regulation and apoptosis. In the present study, we investigated the exact mechanism by which Beclin 1 acts as a bridge between autophagy and cell cycle, when cells are exposed to ionizing radiation (IR). Western blotting and coimmunoprecipitation were performed to investigate protein expression levels and interactions. Immunofluorescence was used to monitor the localization and distribution of the indicated proteins. The levels of apoptosis and cell cycle changes were evaluated by flow cytometry. Double thymidine deoxyribonucleoside (TdR) blocking was conducted to differentiate G2 from mitotic delay. In vitro kinase assays using ATM kinase were performed to elucidate the specific phosphorylation site in Beclin 1. In this study, we show that Beclin 1 knockdown reduces IR-induced autophagy. IR enhanced Beclin 1/PIK3CIII complex activity as demonstrated by the results of coimmunoprecipitation and immunofluorescence assays. An investigation to assess the possible relationship between autophagy and G2/M arrest showed that, similar to the autophagy inhibitor 3MA, Beclin 1 knockdown delayed IR-induced G2/M arrest. Furthermore, the interactions between Beclin 1 and several G2/M checkpoint-related proteins, namely, PLK1 and CDC25C, were observed to increase. In addition, we observed that both 3MA and Beclin 1 inhibition decreased IR-induced apoptosis. Regarding the potential mechanism associated with this phenomenon, we showed that IR induced the interaction between Beclin 1 and Tip60 as well as their redistribution. Furthermore, we demonstrated that Beclin 1 T57 may be a targeted phosphorylation site for ATM. In the present study, we demonstrate the crucial and intricate roles of Beclin 1 in IR-induced autophagy, G2/M cell cycle arrest, and apoptosis. Additionally, Tip60 and ATM were identified as important molecular regulators of Beclin 1. Our findings show the precise mechanism of crosstalk between IR-induced autophagy and G2/M cell cycle arrest. • The roles of Beclin 1 in IR-induced autophagy, G2/M cell cycle arrest, and apoptosis. • Tip60 and ATM were identified as important molecular regulators of Beclin 1. • Beclin 1 mediated the crosstalk between IR-induced autophagy and G2/M cell cycle. [ABSTRACT FROM AUTHOR]

The main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2-like tumor-associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, this study shows that the tumor suppressive protein SHISA3 regulates the antitumor functions of TAMs. Local delivery of mRNA encoding Shisa3 enables cancer immunotherapy by reprogramming TAMs toward an antitumoral phenotype, thus enhancing the efficacy of programmed cell death 1 (PD-1) antibody. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8 + T cell-mediated antitumor immunity. The expression of SHISA3 is induced by damage/pathogen-associated molecular patterns (DAMPs/PAMPs) in macrophages via nuclear factor-κB (NF-κB) transcription factors. Reciprocally, SHISA3 forms a complex with heat shock protein family A member 8 (HSPA8) to activate NF-κB signaling thus maintaining M1 polarization of macrophages. Knockout Shisa3 largely abolishes the antitumor efficacy of combination immunotherapy with Toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and PD-1 antibody. It further found that higher expression of SHISA3 in antitumoral TAMs is associated with better overall survival in lung cancer patients. Taken together, the findings describe the role of SHISA3 in reprogramming TAMs that ameliorate cancer immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Aqueous zinc metal batteries are a viable candidate for next-generation energy storage systems, but suffer from poor cycling efficiency of the Zn anode. Emerging approaches aim to regulate zinc plating behavior to suppress uncontrolled dendrites, while the stripping process is seldom considered. Herein, an oriented metal stripping strategy is demonstrated to stabilize the Zn anode by removing high-index facets for exposing the (002) plane through the addition of anionic additive sodium citrate (SC). Consequently, high-index facets that coordinate strongly with SC are preferentially stripped out due to a reduced stripping barrier, rendering stable (002) facet preponderant in epitaxial plating. After repeat stripping/plating, the ultra-high proportion of 93% for (002) and large-size grains of ≈100 µm (six times larger than before) can be obtained. Zn anode shows continuous 25 000 cycles with low overpotential at 100 mA cm -2 in symmetric cells and more than 70 h of stable operation even at an ultra-high depth of discharge of 92.3%. Moreover, an extremely long lifespan of 12 000 cycles at 10 A g -1 with a high capacity retention of 89% is achieved by the assembled Zn//I 2 battery. This work provides a distinctive approach to improving the stripping process to design highly efficient zinc anodes for promising aqueous zinc metal batteries., (© 2024 Wiley‐VCH GmbH.)

Virus-related diseases are seriously threatening human health, but there are currently only 10 viruses with clinically approved antiviral drugs available. As non-cellular organisms, viruses parasitize in living cells and rely on the protein synthesis mechanism of the host cells. In this study, we found that the antipsychotic drug trifluoperazine (TFP), a dual dopamine receptor D2 (DRD2)/calmodulin (CALM) antagonist, increases the phosphorylation of eukaryotic initiation factor 2α (eIF2α), a key factor in the regulation of protein synthesis and significantly inhibits vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) replication. CALM but not DRD2 is involved in the antiviral activity of TFP. By knockdown of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) we found that the antiviral function of TFP is dependent on PERK, a stress response kinase that mediates eIF2α phosphorylation. Furthermore, the results of animal experiments showed that TFP protects mice from lethal VSV attacks, improving the survival rate and reducing lung injury. Taken together, these data suggests that TFP inhibits virus replication through PERK-eIF2α axis, and this broad-spectrum of mechanisms are worth further evaluation in clinical trials in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mao, Wang, Yao, Zeng, Cheng, Zhang, Chen and Sheng.)

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein β-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of β-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that β-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated β-arrestin 2 expression in human macrophages, and silencing of β-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. β-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, β-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of β-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting β-arrestin 2 to modulate the TLR2-β-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Nonhomologous end joining (NHEJ) and homologous recombination (HR) are major repair pathways of DNA double-strand breaks (DSBs). The pathway choice of HR and NHEJ is tightly regulated in cellular response to DNA damage. Here, we demonstrate that the interaction of TIP60 with DNA-PKcs is attenuated specifically in S phase, which facilitates HR pathway activation. SUMO2 modification of TIP60 K430 mediated by PISA4 E3 ligase blocks its interaction with DNA-PKcs, whereas TIP60 K430R mutation recovers its interaction with DNA-PKcs, which results in abnormally increased phosphorylation of DNA-PKcs S2056 in S phase and marked inhibition of HR efficiency, but barely affects NHEJ activity. TIP60 K430R mutant cancer cells are more sensitive to radiation and PARP inhibitors in cancer cell killing and tumor growth inhibition. Collectively, coordinated regulation of TIP60 and DNA-PKcs facilitates HR pathway choice in S-phase cells. TIP60 K430R mutant is a potential target of radiation and PARPi cancer therapy., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

A cladistic analysis based on 31 morphological characters of female adults recovered two genera currently placed in subfamily Thripinae, Bradinothrips Hood and Parascolothrips Mound, as closely related to two Panchaetothripinae genera, Monilothrips Moulton and Zaniothrips Bhatti. Thus, following the results of this analysis, we propose the transference of the first two genera to subfamily Panchaetothripinae, under the tribe Monilothripini.

Variation is discussed concerning the number of antennal segments in adults, and the number of their sense cones, among 182 of the 289 genera of Thripidae. Brief comments are also made concerning antennal structure and sensoria among the other seven terebrantian families. The plesiotypic condition for Thysanoptera is 9-segmented antennae, but fusion between various segments leads to a reduction in number to as few as five segments, and such fusion occurs in unrelated species. In Thripidae, antennal segment III never bears more than one sense cone, but the distribution of sense cones on segments IV-VIII varies and is tabulated. On antennal segment IV, species in nearly all Panchaetothripinae genera and more than half of Thripinae genera have two sense cones, but genera of Dendrothripinae and Sericothripinae bear only one on this segment. The differing patterns of segmental fusion that occur in Thripidae are discussed in association with the number of sense cones on VI-VIII; species with 7, 8 or 9 segmented antennae almost always lack a sense cone on the terminal segment. It is concluded that the number of antennal segments is subject to irregular homoplasy, and is thus sometimes an unreliable indicator of relationships.