Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Multifunctional Nacre‑Like Nanocomposite Papers for Electromagnetic Interference Shielding via Heterocyclic Aramid/MXene Template‑Assisted In‑Situ Polypyrrole Assembly

Robust, ultra-flexible, and multifunctional MXene-basedelectromagnetic interference (EMI) shielding nanocomposite filmsexhibit enormous potential for applications in artificial intelligence,wireless telecommunication, and portable/wearable electronic equipment.In this work, a nacre-inspired multifunctional heterocyclic aramid(HA)/MXene@polypyrrole (PPy) (HMP) nanocomposite paper withlarge-scale, high strength, super toughness, and excellent tolerance tocomplex conditions is fabricated through the strategy of HA/MXenehydrogel template-assisted in-situ assembly of PPy. Benefiting from the"brick-and-mortar" layered structure and the strong hydrogen-bondinginteractions among MXene, HA, and PPy, the paper exhibits remarkable mechanical performances, including high tensile strength (309.7 MPa),outstanding toughness (57.6 MJ m−3), exceptional foldability, and structural stability against ultrasonication. By using the template effect ofHA/MXene to guide the assembly of conductive polymers, the synthesized paper obtains excellent electronic conductivity. More importantly,the highly continuous conductive path enables the nanocomposite paper to achieve a splendid EMI shielding effectiveness (EMI SE) of 54.1 dBat an ultra-thin thickness (25.4 μm) and a high specific EMI SE of 17,204.7 dB cm2g−1. In addition, the papers also have excellent applicationsin electromagnetic protection, electro-/photothermal de-icing, thermal therapy, and fire safety. These findings broaden the ideas for developinghigh-performance and multifunctional MXene-based films with enormous application potential in EMI shielding and thermal management.

3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

Near-infrared brain functional characteristics of mild cognitive impairment with sleep disorders

BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.

Research on the Construction of Intellectual Property System and Optimization of Business Environment in China

With the rapid development of globalization and information technology,intellectual property has been one of the key drivers of economic growth,and the construction of intellectual property system has become an important criterion for measuring the quality of business environment.This article is intended to explore the current status of intellectual property system construction in China,the challenges,and its relationship with the business environment,to propose the corresponding countermeasures and suggestions.The study finds that the legal system of intellectual property in China is gradually improving,and judicial and administrative protection are continuously strengthened.However,the challenges still remain such as frequent infringements,rights hard to protect and insufficient international cooperation.These issues not only affect the legitimate rights and interests of innovation entities,but also for the market fairness and the level of the business environment.Therefore,this article proposes that strengthening the perfection of the intellectual property legal system,enhancing intellectual property services and support capabilities,strengthening international cooperation and exchanges,and accelerating the cultivation of composite talents.It aims to provide theoretical references for the construction of intellectual property system and the optimization of the business environment,promote the high-quality development of economy and enhance the global competitiveness of the country.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

The Similarity Transformation of Regularizing Functionals and Simularity Property of Their Fourier Transformations

Let and denote respectively the functionswhere λ≥1, The author discusses the similarity transformation of the regularizing functionals of these functions and the similar property of their Fourier transformation.

Effect of Graphene Surface Functional Groups on the Mechanical Property of PMMA Microcellular Composite Foams

The functional groups on graphene sheets surface affect their dispersion and interfacial adhesion in polymer matrix. We compared the mechanical property of polymethymethacrylate（PMMA） microcellular foams reinforced with graphene oxide（GO） and reduced graphene oxide（RGO） to investigate this influence of functional groups. RGO sheets were fabricated by solvent thermal reduction in DMF medium. UV-Vis, FT-IR and XPS analyses indicate the difference of oxygen-containing groups on GO and RGO sheets surface. The observation of SEM illustrates that the addition of a smaller number of GO or RGO sheets causes a fine cellular structure of PMMA foams with a higher cell density(about 1011 cells/cm3) and smaller cell sizes（about 1-2 μm） owing to their remarkable heterogeneous nucleation effect. Compared to GO reinforced foams, the RGO/PMMA foams own lower cell density and bigger cell size in their microstructure, and their compressive strength is lower even when the reinforcement contents are the same and the foam bulk density is higher. These results indicate that the oxygen-containing groups on GO sheets’ surface are beneficial to adhere CO2 to realize a larger nucleation rate, and their strong interaction with PMMA matrix improves the mechanical property of PMMA foams.

Synthesis, Crystal Structure and Anion Recognition Property of a Flexible Urea-functionalized Receptor

A flexible urea-functionalized receptor bearing two p-nitrobenzene units was designed and synthesized from the reaction of precursors 4-nitrophenyl isocyanate and 1,2-bis（2?-aminophenoxy） benzene. The receptor was characterized by 1 H NMR, MS, FTIR and elemental analysis, and the crystal structure of the receptor was determined by X-ray diffraction analysis. The crystal belongs to the orthorhombic system, space group Pca21 with a = 12.740（2）, b =14.133（3）, c = 15.842（3） ?, V = 2852.4（9） ?3, Z = 4, Mr = 620.57, Dc = 1.445 g/cm3, F（000） = 1288,= 0.0585 and wR = 0.1032 for 3177 observed reflections（Ⅰ > 2σ（Ⅰ））, and R = 0.1304 and wR =for all data. The results show that the receptor displays selective recognition ability for H2PO4– in DMSO with a series of anions using UV-Vis absorption spectra technique. Furthermore, the coordination reaction of the receptor with H2PO4– was investigated via UV-Vis spectra and 1 H NMR.The stoichiometric ratio and the association constant（Ka） of the coordination reaction were obtained as well.

Mechanical property and biological behaviour of additive manufactured TiNi functionally graded lattice structure

Bio-inspired porous metallic scaffolds have tremendous potential to be used as artificial bone substitutes.In this work,a radially graded lattice structure (RGLS),which mimics the structures of natural human bones,was designed and processed by laser powder bed fusion of martensitic Ti-rich TiNi powder.The asymmetric tension-compression behaviour,where the compressive strength is significantly higher than the tensile strength,is observed in this Ti-rich TiNi material,which echoes the mechanical behaviour of bones.The morphologies,mechanical properties,deformation behaviour,and biological compatibility of RGLS samples were characterised and compared with those in the uniform lattice structure.Both the uniform and RGLS samples achieve a relative density higher than 99%.The graded porosities and pore sizes in the RGLS range from 40%-80% and 330-805 µm,respectively,from the centre to the edge.The chemical etching has significantly removed the harmful partially-melted residual powder particles on the lattice struts.The compressive yield strength of RGLS is 71.5 MPa,much higher than that of the uniform sample (46.5 MPa),despite having a similar relative density of about 46%.The calculated Gibson-Ashby equation and the deformation behaviour simulation by finite element suggest that the dense outer regions with high load-bearing capability could sustain high applied stress,improving the overall strength of RGLS significantly.The cell proliferation study suggests better biological compatibility of the RGLS than the uniform structures.The findings highlight a novel strategy to improve the performance of additively manufactured artificial implants by bio-inspiration.

A Novel Copper(Ⅱ) Complex of Asymmetrically N-Functionalized 1,4,7-Triazacyclononane Ligand： Syntheses, Structure, Electrochemical Property and Biological Activities

A novel copper（Ⅱ） complex derived from 1,4,7-triazacyclononane[CuL]_2（PF_6）_3×MeCN×H_2 O was synthesized and crystallographically characterized {L = 1,4-bis（2-carbamoylethyl）-7-benzimidazole-2-yl-methyl-1,4,7-triazacyclononane}. It crystallizes in triclinic, space group P1, with a = 13.2425（13）, b = 14.0807（15）, c = 17.6798（18）, α = 86.296（2）, β = 72.773（2）, γ= 68.905（2）o, V = 2934.5（5）A^3, Z = 2, D_c = 1.611 g/m^3, F（000） = 1456, M_r = 1423.09, m = 0.920 mm^-1. The final R = 0.0671 and wR = 0.1874 for 6501 observed reflections with I 〉 2σ（I）. The structural analysis shows that the complex cation（[CuL]_2^3＋） was formed by two complex cations, namely（[CuL^3]^2＋） and [CuL_（-H）~3]~＋） through a hydrogen bond. In each complex cation, the Cu（Ⅱ） lies in a distorted square pyramidal geometry. The redox behavior was studied by cyclic voltammetry（CV） in aqueous solution which indicates a reversible one electron redox reaction. The result of UV absorption, ethidium bromide（EB） fluorescence spectra indicated that the complex binds to CT-DNA in an intercalative mode. Superoxide dismutase（SOD） activity of the complex was determined by photoreduction of NBT, and the value of IC_（50） is 5.22 μmol·L^-1.

Synthesis, Crystal Structure and Luminescent Property of Ladder-shaped Zinc Coordination Polymer with Mixed Polyfunctional Ligands

One new Zn（Ⅱ） complex [Zn2（cptpy）2（tzba）（H2O）]·H2O（1, Hcptpy = 4-（4-carboxyphenyl）-2,2＇：4＇,4＇＇-terpyridine（Hcptpy）, H_2tzba = 4-（tetrazol-5-yl）benzenecarboxylic acid） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction techniques. It is formulated as C52H36O8N10Zn2, crystallizes in monoclinic system, space group P21/c with α = 15.1599（13）, b = 28.083（2）, c = 10.9039（9） A, b = 97.517（8）o. V = 4602.3（6） A^3, Z = 4, Mr = 1059.68, Dc = 1.529 g/cm^3, F（000） = 2168 and μ = 1.112 mm^-1. The final R = 0.0831 and wR = 0.2143 for 8458 observed reflections with I 〉 2s（I）. The assembly of polyfunctional organic ligands Hcptpy and H_2tzba with Zn（II） atoms resulting in a rare example of double-edge ladders, which is further extended into a 3D supramolecular network via O–H…O/N hydrogen bonds. In addition, thermal gravimetric analysis（TGA） and PXRD patterns for 1 were studied. Photo luminescent property of 1 was also investigated.

Surface functional groups and redox property of modified activated carbons

A series of activated carbons（ACs） were prepared using HNO_3,H_2O_2 and steam as activation agents with the aim to introduce functional groups to carbon surface in the ACs preparation process.The effects of concentration of activation agent,activation time on the surface functional groups and redox property of ACs were characterized by Temperature Program Desorption（TPD） and Cyclic Voltammetry（CV）.Results showed that lactone groups of ACs activated by HNO_3 increase with activation time,and the carboxyl groups increase with the concentration of HNO_3.Carbonyl/quinine groups of ACs activated by H_2O_2 increase with the activation time and the concentration of H_2O_2,although the acidic groups decrease with the concentration of H_2O_2.The redox property reflected by CV at 0 and 0.5 V is different with any kinds of oxygen functional groups characterized by TPD,but it is consistent with the SO_2 catalytic oxidization /oxidation properties indicated by TPR.

Interfacial Charge Transfer Induced Electronic Property Tuning of MoS_2 by Molecular Functionalization

The modulation of electrical properties of MoS_2 has attracted extensive research interest because of its potential applications in electronic and optoelectronic devices.Herein,interfacial charge transfer induced electronic property tuning of MoS_2 are investigated by in situ ultraviolet photoelectron spectroscopy and x-ray photoelectron spectroscopy measurements.A downward band-bending of MoS_2-related electronic states along with the decreasing work function,which are induced by the electron transfer from Cs overlayers to MoS_2,is observed after the functionalization of MoS_2 with Cs,leading to n-type doping.Meanwhile,when MoS_2 is modified with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane(F_4-TCNQ),an upward band-bending of MoS_2-related electronic states along with the increasing work function is observed at the interfaces.This is attributed to the electron depletion within MoS_2 due to the strong electron withdrawing property of F_4-TCNQ,indicating p-type doping of MoS_2.Our findings reveal that surface transfer doping is an effective approach for electronic property tuning of MoS_2 and paves the way to optimize its performance in electronic and optoelectronic devices.

Combining stochastic density functional theory with deep potential molecular dynamics to study warm dense matter

In traditional finite-temperature Kohn–Sham density functional theory(KSDFT),the partial occupation of a large number of high-energy KS eigenstates restricts the use of first-principles molecular dynamics methods at extremely high temperatures.However,stochastic density functional theory(SDFT)can overcome this limitation.Recently,SDFT and the related mixed stochastic–deterministic density functional theory,based on a plane-wave basis set,have been implemented in the first-principles electronic structure software ABACUS[Q.Liu and M.Chen,Phys.Rev.B 106,125132(2022)].In this study,we combine SDFT with the Born–Oppenheimer molecular dynamics method to investigate systems with temperatures ranging from a few tens of eV to 1000 eV.Importantly,we train machine-learning-based interatomic models using the SDFT data and employ these deep potential models to simulate large-scale systems with long trajectories.Subsequently,we compute and analyze the structural properties,dynamic properties,and transport coefficients of warm dense matter.