The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.

Cytomegalovirus (CMV) has successfully established a long-lasting latent infection in humans due to its ability to counteract the host antiviral innate immune response. During coevolution with the host, the virus has evolved various evasion techniques to evade the host's innate immune surveillance. At present, there is still no vaccine available for the prevention and treatment of CMV infection, and the interaction between CMV infection and host antiviral innate immunity is still not well understood. However, ongoing studies will offer new insights into how to treat and prevent CMV infection and its related diseases. Here, we update recent studies on how CMV evades antiviral innate immunity, with a focus on how CMV proteins target and disrupt critical adaptors of antiviral innate immune signaling pathways. This review also discusses some classic intrinsic cellular defences that are crucial to the fight against viral invasion. A comprehensive review of the evasion mechanisms of antiviral innate immunity by CMV will help investigators identify new therapeutic targets and develop vaccines against CMV infection.

Levodopa-induced dyskinesia: brain iron deposition as a new hypothesis.

Parkinson's disease (PD) is a common neurodegenerative disease in the older adults. The main pathological change in PD is the degenerative death of dopamine (DA) neurons in the midbrain substantia nigra, which causes a significant decrease in the DA content of the striatum. However, the exact etiology of this pathological change remains unclear. Genetic factors, environmental factors, aging, and oxidative stress may be involved in the degenerative death of dopaminergic neurons in PD. Pharmacological treatment using levodopa (L-DOPA) remains the main treatment for PD. Most patients with PD consuming L-DOPA for a long time usually develop levodopa-induced dyskinesia (LID) after 6.5 years of use, and LID seriously affects the quality of life and increases the risk of disability. Recently, studies have revealed that cerebral iron deposition may be involved in LID development and that iron deposition has neurotoxic effects and accelerates disease onset. However, the relationship between cerebral iron deposition and LID remains unclear. Herein, we reviewed the mechanisms by which iron deposition may be associated with LID development, which are mainly related to oxidative stress, neuroinflammation, and mitochondrial and lysosomal dysfunction. Using iron as an important target, the search and development of safe and effective brain iron scavengers, and thus the alleviation and treatment of LID, has a very important scientific and clinical value, as well as a good application prospect.

[Three-dimensional finite element analysis of lumbar disc herniation under different body positions].

OBJECTIVE: To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation (LDH) by finite element analysis. METHODS: Lumbar CT image of a 48-year-old female patient with LDH (heighted 163 cm, weighted 53 kg) was collected. Mimics 20.0, Geomagic Studio, Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments. Compression techniques under horizontal position, 30° forward bending and 10° backward extension were simulated respectively. After applying the pressure, the effects of compression techniques under different positions on stress, strain and displacement of various tissues of intervertebral disc and nerve root were observed. RESULTS: L4, 5 segment finite element model was successfully established, and the model was validated. When compression manipulation was performed on the horizontal position, 30° flexion and 10° extension, the annular stress were 0.732, 5.929, 1.286 MPa, the nucleus pulposus stress were 0.190, 1.527, 0.295 MPa, and the annular strain were 0.097, 0.922 and 0.424, the strain sizes of nucleus pulposus were 0.153, 1.222 and 0.282, respectively. The overall displacement distance of intervertebral disc on Y direction were -3.707, -18.990, -4.171 mm, and displacement distance of nerve root on Y direction were +7.836, +5.341, +3.859 mm, respectively. The relative displacement distances of nerve root and intervertebral disc on Y direction were 11.543, 24.331 and 8.030 mm, respectively. CONCLUSION: Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend, by increasing the distance between herniated intervertebral disc and nerve root, to reduce symptoms of nerve compression, to achieve purpose of treatment for patients with LDH, in which the compression manipulation is more effective when the forward flexion is 30°.

Shear Field-Controlled Synthesis of Nitrogen-Doped Carbon Nanochains Forest with High-Density sp3 Defects for Efficient CO2 Electroreduction Reaction.

Defect engineering and nitrogen doping being effective strategies for modulating the surface chemical state of the carbon matrix have been widely explored to promote the catalytic activity in the territory of electrochemical energy storage and conversion devices. However, the controllable synthesis of carbon material with high-density specific defects and high nitrogen doping is still full of challenges. Here, we first synthesize one-dimensional necklace-like nitrogen-doped carbon nanochains (N-CNCs) with abundant defects on carbon fiber paper (CFP) by chemical vapor deposition (CVD) method. The resultant nanostructures are a bunch of interconnected carbon spheres with a hollow structure at the internode and present the complete one-dimensional nanochain configuration. Specifically, the N-CNCs with a corrugated surface possesses high content of sp3 defects (31.2%) and nitrogen (23.6 at %). Combining finite element analysis and experimental results, it reveals that the robust shear field generated by etching gas releasing from thermal decomposition of melamine in situ modulates the CVD process via changing the size and force environment of the metal catalyst droplets for formation of N-CNCs. Benefiting from the high ratio of sp3/sp2 and nitrogen doped on the surface, the N-CNCs@CFP displays a superior electrocatalytic performance for CO2RR, delivering CO Faradaic efficiency of 95.9% and a current density of 23.2 mA cm-2 at -0.86 V vs RHE. This work provides promising synthesis strategy and some inspirations for construction of ultradense and specific defects coupling with nitrogen doping sites into carbon materials to achieve high-efficiency electrocatalysis applications.

Microscopic-Level Insights into P-O-Induced Strong Electronic Coupling Over Nickel Phosphide with Efficient Benzyl Alcohol Electrooxidation.

Electrooxidation of biomass into fine chemicals coupled with energy-saving hydrogen production for a zero-carbon economy holds great promise. Advanced anode catalysts determine the cell voltage and electrocatalytic efficiency greatly, further the rational design and optimization of their active site coordination remains a challenge. Herein, a phosphorus-oxygen terminals-rich species (Ni2P-O-300) via an anion-assisted pyrolysis strategy is reported to induce strong electronic coupling and high valence state of active nickel sites over nickel phosphide. This ultimately facilitates the rapid yet in-situ formation of high-valence nickel with a high reaction activity under electrochemical conditions, and exhibits a low potential of 1.33 V vs. RHE at 10 mA cm-2, exceeding most of reported transition metal-based catalysts. Advanced spectroscopy, theoretical calculations, and experiments reveal that the functional P-O species can induce the favorable local bonding configurations for electronic coupling, promoting the electron transfer from Ni to P and the adsorption of benzyl alcohol (BA). Finally, the hydrogen production efficiency and kinetic constant of BA electrooxidation by Ni2P-O-300 are increased by 9- and 2.8- fold compared with the phosphorus-oxygen terminals-deficient catalysts (Ni2P-O-500). This provides an anion-assisted pyrolysis strategy to modulate the electronic environment of the Ni site, enabling a guideline for Ni-based energy/catalysis systems.

Recent Advances in Low-Temperature Liquid Electrolyte for Supercapacitors.

As one of the key components of supercapacitors, electrolyte is intensively investigated to promote the fast development of the energy supply system under extremely cold conditions. However, high freezing point and sluggish ion transport kinetics for routine electrolytes hinder the application of supercapacitors at low temperatures. Resultantly, the liquid electrolyte should be oriented to reduce the freezing point, accompanied by other superior characteristics, such as large ionic conductivity, low viscosity and outstanding chemical stability. In this review, the intrinsically physical parameters and microscopic structure of low-temperature electrolytes are discussed thoroughly, then the previously reported strategies that are used to address the associated issues are summarized subsequently from the aspects of aqueous and non-aqueous electrolytes (organic electrolyte and ionic liquid electrolyte). In addition, some advanced spectroscopy techniques and theoretical simulation to better decouple the solvation structure of electrolytes and reveal the link between the key physical parameters and microscopic structure are briefly presented. Finally, the further improvement direction is put forward to provide a reference and guidance for the follow-up research.

A Ferricyanide Anion-Philic Interface Induced by Boron Species within Carbon Framework for Efficient Charge Storage in Supercapacitors.

Carbon materials with hierarchical porous structures hold great potential for redox electrolyte-enhanced supercapacitors. However, restricted by the intrinsic inert and nonpolar characteristics of carbon, the energy barrier of anchoring redox electrolytes on the pore walls is relatively high. As such, the redox process at the interface less occurs, and the rate of mass transfer is impaired, further leading to a poor electrochemical performance. Here, a ferricyanide anion-philic interface made of in situ inserted boron species into carbon rings is constructed for enhanced charge storage in supercapacitors. Profiting from the unique component-driven effects, the polar anchoring sites on the pore wall can be built to grasp the charged redox ferricyanide anion from the bulk electrolyte and promote the redox process; the dynamics process is fastened correspondingly. Especially, the boron atoms in BC2O and BCO2 units with higher positive natural bond orbital values in the carbon skeleton are pinpointed as intrinsic active sites to bind the negatively charged nitrogen atoms in the ferricyanide anion via electrostatic interaction, confirmed by density functional theoretical calculations. This will suppress the shuttle and diffusion effects of the ferricyanide anion from the surface of the electrode to the bulk electrolyte. Finally, the well-designed PC-3 with high content of BC2O and BCO2 units can reach 1099 F g-1 at 2 mV s-1, which is a more than 2-fold increase over boron-free units of carbon (428 F g-1). The work offers a novel version for designing high-performance carbon materials with unique yet reaction species-philic effects.

FeOOH with Low Spin State Iron as Electron Acceptors for High Yield Rate Electrosynthesis of Urea from Nitrate and Carbon Dioxide.

Co electroreduction of carbon dioxide and nitrate to synthesize urea provides an alternative strategy to high energy-consumption traditional methods. However, the complexity of the reaction mechanism and the high energy barrier of nitrate reduction result in a diminished production of urea. Herein, a convenient electrodeposition technique to prepare the FeOOH with low spin state iron that increases the yield rate of urea efficiently is employed. According to soft X-ray Absorption Spectroscopy and theoretical calculations, the unique configuration of low spin state iron as electron acceptors can effectively induce electron pair transfer from the occupied σ orbitals of intermediate * NO to empty d orbitals of iron. This σ→d donation mechanism leads to a reduction in the energy barrier associated with the rate-determining step (* NOOH→* NO + * OH), hence augmenting the urea generation. The low spin state iron presents a high urea yield rate of 512 µg h-1  cm-2 , representing approximately two times compared to the medium spin state iron. The key intermediates (* NH2 and * CO) in the formation of C─N bond are detected with in situ Fourier transform infrared spectroscopy. The coupling of * NH2 and * CO contributes to the formation of * CONH2 , which subsequently endures multi-step proton-coupled electron transfer to generate urea.

NFYB increases chemosensitivity in glioblastoma by promoting HDAC5-mediated transcriptional inhibition of SHMT2.

Temozolomide (TMZ) is a commonly used chemotherapeutic agent for glioblastoma (GBM), but acquired drug resistance prevents its therapeutic efficacy. We investigated potential mechanisms underlying TMZ resistance and glycolysis in GBM cells through regulation by nuclear transcription factor Y subunit ß (NFYB) of the oncogene serine hydroxymethyltransferase 2 (SHMT2). GBM U251 cells were transfected with NFYB-, SHMT2-, and the potential NFYB target histone deacetylase 5 (HDAC5)-related vectors. Glucose uptake and lactate production were measured with detection kits. CCK-8/colony formation, scratch, Transwell, and flow cytometry assays were performed to detect cell proliferation, migration, invasion, and apoptosis, respectively. The binding of NFYB to the HDAC5 promoter and the regulation of NFYB on HDAC5 promoter activity were detected with chromatin immunoprecipitation and dual-luciferase reporter assays, respectively. NFYB and HDAC5 were poorly expressed and SHMT2 was expressed at high levels in GBM U251 cells. NFYB overexpression or SHMT2 knockdown decreased glucose uptake, lactate production, proliferation, migration, and invasion and increased apoptosis and TMZ sensitivity of the cells. NFYB activated HDAC5 to inhibit SHMT2 expression. SHMT2 overexpression nullified the inhibitory effects of NFYB overexpression on glycolysis and TMZ resistance. Thus, NFYB may reduce tumorigenicity and TMZ resistance of GBM through effects on the HDAC5/SHMT2 axis.

Processable Hydroxide Ink with Oriented Microstructure.

The intrinsic poor processability of hydroxide originating from the structural property greatly hinders their practical applications. Here, a processable highly-concentrated nickel/cobalt double hydroxide ink is reported to meet the practical demand. The inner nanoflakes in ink possess a high width/thickness ratio (>100), which endows the highly-concentrated ink (60 mg mL-1 ) with liquid-like rheology properties. Further, the elliptical diffusive arc in small-angle X-ray scattering pattern and porous and ordered alignment morphology in cryogenic temperature scanning electron microscopy confirms the locally oriented arrangement of nanoflakes in the ink. Benefiting from this interior-ordered structure, the ink can be processed into meter-level film, continuous yarn, and rigid and free-standing aerogel, respectively. In particular, the films can be used as electrodes directly in aqueous zinc ion batteries and deliver a favorable capacity (382 mAh g-1 @ 200 mA g-1 ) as well as long cycle stability (capacity retention rate of 88% @ 1000 mA g-1 after 400 cycles). Moreover, the enlarged-batched fabrication with the introduction of efficient thermal conduction in a 10 L reactor is also carried out successfully. These results clarify the inner relationship between microstructure-rheology and mechanical engineering for hydroxides, thus paving the way to develop hydroxide-based products for future practical applications.

Microscopic-Level Insights into Solvation Chemistry for Nonsolvating Diluents Enabling High-Voltage/Rate Aqueous Supercapacitors.

Localized "water-in-salt" (LWIS) electrolytes are promising candidates for the next generation of high-voltage aqueous electrolytes with low viscosity/salt beyond high-salt electrolytes. An effective yet high-function diluent mainly determines the properties of LWIS electrolytes, being a key issue. Herein, the donor number of solvents is identified to serve as a descriptor of interaction intensity between solvents and salts to screen the organic diluents having few impacts on the solvation microenvironment and intrinsic properties of the original high-salt electrolyte, further leading to the construction of a novel low-viscosity electrolyte with a low dosage of the LiNO3 salt and well-kept intrinsic Li+-NO3--H2O clusters. Nonsolvating diluents, especially acetonitrile (AN) that has never been reported previously, are presented with the capability of constructing a LWIS electrolyte with nonflammability, electrode-philic features, lower viscosity, decreased salt dosage, and a greatly enhanced ion diffusion coefficient by about 280 times. This strongly relies on a huge difference of about 5000 times in coordination and solubility between AN and H2O toward LiNO3 (0.05 vs 25 mol kgsolvent-1) and the moderate interaction between AN and H2O. Multi-spectroscopic techniques and molecular dynamics simulations uncover the solvation chemistry at the microscopic level and the interplay among cations, anions, and H2O without/with AN. The identified unique diluting and nonsolvating effects of AN reveal well-maintained cation-anion-H2O clusters and enhanced intermolecular hydrogen bonding between AN and H2O, further reinforcing the H2O stability and expanding the voltage window up to 3.28 V. This is a breakthrough that is far beyond high-viscosity/salt electrolytes for high-voltage and high-rate aqueous supercapacitors.

Broadband Transient Response and Wavelength-Tunable Photoacoustics in Plasmonic Hetero-nanoparticles.

The optically driven acoustic modes and nonlinear response of plasmonic nanoparticles are important in many applications, but are strongly resonant, which restricts their excitation to predefined wavelengths. Here, we demonstrate that multilayered spherical plasmonic hetero-nanoparticles, formed by alternating layers of gold and silica, provide a platform for a broadband nonlinear optical response from visible to near-infrared wavelengths. They also act as a tunable optomechanical system with mechanically decoupled layers in which different acoustic modes can be selectively switched on/off by tuning the excitation wavelength. These observations not only expand the knowledge about the internal structure of composite plasmonic nanoparticles but also allow for an additional degree of freedom for controlling their nonlinear optical and mechanical properties.

pH-Switchable Pickering miniemulsion enabled by carbon quantum dots for quasi-homogenized biphasic catalytic system.

A quasi-homogenized miniemulsion system enabled by carbon quantum dot solid nanoparticles for biphasic catalysis is proposed, which breaks existing limits for an immiscibly biphasic system and overcomes issues for large-sized solid particle-stabilized emulsion droplets. The presented Pickering miniemulsion features pH-responsive behavior, finally triggering facile product separation and catalyst recycling in one reaction vessel.

Carbon-Hybridized Hydroxides for Energy Conversion and Storage: Interface Chemistry and Manufacturing.

Carbon-hybridized hydroxides (CHHs) have been intensively investigated for uses in the energy conversion/storage fields. Nevertheless, the intrinsic structure-activity relationships between carbon and hydroxides within CHHs are still blurry, which hinders the fine modulation of CHHs in terms of practical applications to some degree. This review aims to figure out the intrinsic role of carbon materials in CHHs with a focus on the interface chemistry and the engineering strategy in-between two components. The fundamental effects of the carbon materials in enhancing the charge/mass transfer kinetics are first analyzed, particularly the extra electron pathways for fast charge transfer and the anchoring sites for boosting the mass transfer. Subsequently, the surface-guided/confined effects of carbon materials in CHHs to modify the morphology and tailor the hydroxides, and functional heterojunction for regulating the inner electronic structure are decoupled. The methods to efficiently construct a stable yet robust solid-solid heterointerface are summarized, including oxygen functional groups engrafting, topological defective sites construction and heteroatom incorporation to activate the inert carbon surface. The smart CHHs in some typical energy applications are demonstrated. Additionally, the methodologies that can reveal the hybridization electron configuration between two components are summed up. At last, the perspective and challenges faced by the CHHs for energy-related applications are outlined.

Inhibition of Glycogen Synthase Kinase 3ß Activity in the Basolateral Amygdala Disrupts Reconsolidation and Attenuates Heroin Relapse.

Exposure to a heroin-associated conditioned stimulus can reactivate drug reward memory, trigger drug cravings, and induce relapse in heroin addicts. The amygdala, a brain region related to emotions and motivation, is involved in processing rewarding stimulus. Recent evidence demonstrated that disrupting the reconsolidation of the heroin drug memories attenuated heroin seeking which was associated with the basolateral amygdala (BLA). Meanwhile, neural functions associated with learning and memory, like synaptic plasticity, are regulated by glycogen synthase kinase 3 beta (GSK-3ß). In addition, GSK-3ß regulated memory processes, like retrieval and reconsolidation of cocaine-induced memory. Here, we used a heroin intravenous self-administration (SA) paradigm to illustrate the potential role of GSK-3ß in the reconsolidation of drug memory. Therefore, we used SB216763 as a selective inhibitor of GSK-3ß. We found that injecting the selective inhibitor SB216763 into the BLA, but not the central amygdala (CeA), immediately after heroin-induced memory retrieval disrupted reconsolidation of heroin drug memory and significantly attenuated heroin-seeking behavior in subsequent drug-primed reinstatement, suggesting that GSK-3ß is critical for reconsolidation of heroin drug memories and inhibiting the activity of GSK-3ß in BLA disrupted heroin drug memory and reduced relapse. However, no retrieval or 6 h after retrieval, administration of SB216763 into the BLA did not alter heroin-seeking behavior in subsequent heroin-primed reinstatement, suggesting that GSK-3ß activity is retrieval-dependent and time-specific. More importantly, a long-term effect of SB216763 treatment was observed in a detectable decrease in heroin-seeking behavior, which lasted at least 28 days. All in all, this present study demonstrates that the activity of GSK-3ß in BLA is required for reconsolidation of heroin drug memory, and inhibiting GSK-3ß activity of BLA disrupts reconsolidation and attenuates heroin relapse.

Mismatching integration-enabled strains and defects engineering in LDH microstructure for high-rate and long-life charge storage.

Layered double hydroxides (LDH) have been extensively investigated for charge storage, however, their development is hampered by the sluggish reaction dynamics. Herein, triggered by mismatching integration of Mn sites, we configured wrinkled Mn/NiCo-LDH with strains and defects, where promoted mass & charge transport behaviors were realized. The well-tailored Mn/NiCo-LDH displays a capacity up to 518 C g-1 (1 A g-1), a remarkable rate performance (78%@100 A g-1) and a long cycle life (without capacity decay after 10,000 cycles). We clarified that the moderate electron transfer between the released Mn species and Co2+ serves as the pre-step, while the compressive strain induces structural deformation with promoted reaction dynamics. Theoretical and operando investigations further demonstrate that the Mn sites boost ion adsorption/transport and electron transfer, and the Mn-induced effect remains active after multiple charge/discharge processes. This contribution provides some insights for controllable structure design and modulation toward high-efficient energy storage.

Clinical characteristics, surgical management, and prognostic factors for supratentorial hemangioblastoma: A retrospective study.

Background: Supratentorial hemangioblastoma is an extremely rare neoplasm. The aim of this study is to delineate the clinical features among cystic and solid supratentorial hemangioblastoma patients and evaluate the risk factors for progression-free survival (PFS). Methods: We conducted a literature search in PubMed for histopathologically identified supratentorial hemangioblastoma between 1947 and 2021 and extracted and collected the clinical features of patients treated at our own institute. The rate of PFS was determined using Kaplan-Meier analysis. Differences in categorical factors, such as the location of tumor and diagnosis of von Hippel-Lindau disease, were analyzed using the Pearson χ 2 test. A Cox regression analysis was performed to evaluate the association between various variates and survival outcomes. Results: A total of 237 cases of supratentorial hemangioblastoma were identified from 169 studies. A survival analysis found that patients with cystic tumors had a significantly better prognosis than those with solid tumors (log-rank, p = 0.0122). Cox regression analysis suggested that cystic hemangioblastoma (hazard ratio (HR): 0.186, 95% CI: 0.043-0.803, p < 0.05) and gross total resection (GTR) (HR: 0.126, 95% CI: 0.049-0.323, p < 0.001) were significant predictors of longer survival (PFS) for supratentorial hemangioblastoma. Following an analysis of 13 supratentorial hemangioblastoma cases from our institute, we validated that cystic tumor had improved prognosis than solid tumor (log-rank, p = 0.0096) and GTR was superior to subtotal resection (log-rank, p = 0.0029). Conclusions: Cystic hemangioblastoma vs. solid hemangioblastoma may be two tumoral statuses with different clinical features, and a specific treatment strategy should be considered.

Efficacy of the Suboccipital Paracondylar-Lateral Cervical Approach: The Series of 64 Jugular Foramen Tumors Along With Follow-Up Data.

OBJECTIVE: Complete resection of jugular foramen tumors with minimal cranial nerve complications remains challenging even for skilled neurosurgeons. Here, we introduce a modified paracondylar approach, named the suboccipital paracondylar-lateral cervical (SPCLC) approach for this purpose. We also share the follow-up data of our series and discuss the advantages and limitations of this modified paracondylar approach. METHODS: We included 64 patients with jugular foramen tumors who underwent surgery by the same senior neurosurgeon between November 2011 and August 2020. All patients were treated with the SPCLC approach, which aimed for gross total tumor removal in a single-stage operation. The clinical characteristics, including preoperative and postoperative neurological status, the extent of surgical resection, and follow-up data were retrospectively acquired and evaluated. RESULTS: There were 48 schwannomas, nine meningiomas, three paragangliomas, one hemangiopericytoma, one chordoma, one endolymphatic sac tumor, and one Langerhans' cell histiocytosis. The median age of our patients was 43 years (range: 21-77 years). Dysphagia, hoarseness, and tongue deviation were observed in 36, 26, and 28 patients, respectively. Thirty-two patients had hearing function impairments, including hearing loss or tinnitus. Gross total resection was achieved in 59 patients (59/64, 92.2%). Gamma Knife treatment was used to manage residual tumors in five patients. Postoperatively, new-onset or aggravative dysphagia and hoarseness occurred in 26 and 18 cases, respectively. Nine patients developed new-onset facial palsy, and one patient developed new-onset hearing loss. There were no cases of intracranial hematoma, re-operation, tracheostomy, or death. At the latest follow-up, hearing loss and tinnitus had improved in 20 cases (20/32, 62.5%), dysphagia alleviated in 20 cases (20/36, 55.6%), and hoarseness improved in 14 cases (14/26, 53.8%). Over a mean follow-up period of 27.8 ± 19.5 months (range: 3-68 months), tumor recurrence was observed in one patient. CONCLUSION: The SPCLC approach, modified from the paracondylar approach, and was less invasive, safe, and efficient for certain jugular foramen tumors. Taking advantage of the anatomic understanding, clear operational vision, and appropriate surgical skills, it is possible to achieve gross total tumor removal and the preservation of neurological function.