Combinatorial therapies for spinal cord injury repair

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

Secretome of polarized macrophages:potential for targeting inflammatory dynamics in spinal cord injury

Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

Perceptions and emotions in postoperative recovery of patients with perianal diseases

This article examines the complex relationship between disease perception,negative emotions,and their impact on postoperative recovery in patients with perianal diseases.These conditions not only cause physical discomfort,but also carry a significant emotional burden,often exacerbated by social stigma.Psycho-logical factors,including stress,anxiety,and depression,activate neuroendocrine pathways,such as the hypothalamic–pituitary–adrenal axis,disrupting the gut microbiota and leading to dysbiosis.This disruption can delay wound healing,prolong hospital stay,and intensify pain.Drawing on the findings of Hou et al,our article highlights the critical role of illness perception and negative emotions in shaping recovery outcomes.It advocates for a holistic approach that integrates psychological support and gut microbiota modulation,to enhance healing and improve overall patient outcomes.

Direct Photolithography of WO_(x) Nanoparticles for High‑Resolution Non‑Emissive Displays

High-resolution non-emissive displays based on electrochromic tungsten oxides(WOx)are crucial for future near-eye virtual/augmented reality interactions,given their impressive attributes such as high environmental stability,ideal outdoor readability,and low energy consumption.However,the limited intrinsic structure of inorganic materials has presented a significant challenge in achieving precise patterning/pixelation at the micron scale.Here,we successfully developed the direct photolithography for WOx nanoparticles based on in situ photo-induced ligand exchange.This strategy enabled us to achieve ultra-high resolution efficiently(line width<4μm,the best resolution for reported inorganic electrochromic materials).Additionally,the resulting device exhibited impressive electrochromic performance,such as fast response(<1 s at 0 V),high coloration efficiency(119.5 cm^(2) C^(−1)),good optical modulation(55.9%),and durability(>3600 cycles),as well as promising applications in electronic logos,pixelated displays,flexible electronics,etc.The success and advancements presented here are expected to inspire and accelerate research and development(R&D)in high-resolution non-emissive displays and other ultra-fine micro-electronics.

Recognition and quality mapping of traditional herbal drugs:way forward towards artificial intelligence

The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.

Spontaneous Orientation Polarization of Anisotropic Equivalent Dipoles Harnessed by Entropy Engineering for Ultra‑Thin Electromagnetic Wave Absorber

The synthesis of carbon supporter/nanoscale high-entropy alloys(HEAs)electromagnetic response composites by carbothermal shock method has been identified as an advanced strategy for the collaborative competition engineering of conductive/dielectric genes.Electron migration modes within HEAs as manipulated by the electronegativity,valence electron configurations and molar proportions of constituent elements determine the steady state and efficiency of equivalent dipoles.Herein,enlightened by skin-like effect,a reformative carbothermal shock method using carbonized cellulose paper(CCP)as carbon supporter is used to preserve the oxygencontaining functional groups(O·)of carbonized cellulose fibers(CCF).Nucleation of HEAs and construction of emblematic shell-core CCF/HEAs heterointerfaces are inextricably linked to carbon metabolism induced by O·.Meanwhile,the electron migration mode of switchable electronrich sites promotes the orientation polarization of anisotropic equivalent dipoles.By virtue of the reinforcement strategy,CCP/HEAs composite prepared by 35%molar ratio of Mn element(CCP/HEAs-Mn_(2.15))achieves efficient electromagnetic wave(EMW)absorption of−51.35 dB at an ultra-thin thickness of 1.03 mm.The mechanisms of the resulting dielectric properties of HEAs-based EMW absorbing materials are elucidated by combining theoretical calculations with experimental characterizations,which provide theoretical bases and feasible strategies for the simulation and practical application of electromagnetic functional devices(e.g.,ultra-wideband bandpass filter).

A Geometric Model Simplification Strategy for CFD Simulation of the Cockpit Internal Environment

Computational Fluids Dynamics(CFD)simulations are essential for optimizing the design of a cockpit’s internal environment,but the complex geometric models consume a significant amount of computational resources and time.Arbitrary simplification of geometric models may result in inaccurate calculations of physical fields.To address this issue,this study establishes a geometric model simplification strategy and successfully applies it to a cockpit.The implementation of the whole approach is divided into three steps,summarized in three methods,namely Sensitivity Analysis Method(SAM),Detail Suppression Method(DSM),and Evaluation Standards Method(ESM).Sensitivity analysis of the detailed features of the geometric model is performed using the adjoint method.The details of the geometric model are suppressed based on the principle of curvature continuity.After evaluation,the suppression degrees of detailed features with different sensitivity levels are obtained.The results demonstrate that this strategy can be employed to achieve precise simplification standards,thereby avoiding excessive deviations caused by arbitrary simplification and reducing the significant costs associated with trial-and-error simplification.

Efficacy of sodium-glucose cotransporter-2 inhibitors and glucagonlike peptide-1 receptor agonists on proteinuria and weight in a diabetes cohort

BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.

Machine learning based damage state identification:A novel perspective on fragility analysis for nuclear power plants considering structural uncertainties

Seismic fragility analysis(SFA)is known as an effective probabilistic-based approach used to evaluate seismic fragility.There are various sources of uncertainties associated with this approach.A nuclear power plant(NPP)system is an extremely important infrastructure and contains many structural uncertainties due to construction issues or structural deterioration during service.Simulation of structural uncertainties effects is a costly and time-consuming endeavor.A novel approach to SFA for the NPP considering structural uncertainties based on the damage state is proposed and examined.The results suggest that considering the structural uncertainties is essential in assessing the fragility of the NPP structure,and the impact of structural uncertainties tends to increase with the state of damage.Subsequently,machine learning(ML)is found to be superior in high-precision damage state identification of the NPP for reducing the time of nonlinear time-history analysis(NLTHA)and could be applied in the damage state-based SFA.Also,the impact of various sources of uncertainties is investigated through sensitivity analysis.The Sobol and Shapley additive explanations(SHAP)method can be complementary to each other and able to solve the problem of quantifying seismic and structural uncertainties simultaneously and the interaction effect of each parameter.

From earthquake resistance structure to earthquake resilience city–urban seismic resilience assessment

Earthquakes pose significant perils to the built environment in urban areas.To avert the calamitous aftermath of earthquakes,it is imperative to construct seismic resilient cities.Due to the intricacy of the concept of urban seismic resilience(USR),its assessment is a large-scale system engineering issue.The assessment of USR should be based on the notion of urban seismic capacity(USC)assessment,which includes casualties,economic loss,and recovery time as criteria.Functionality loss is also included in the assessment of USR in addition to these criteria.The assessment indicator system comprising five dimensions(building and lifeline infrastructure,environment,society,economy,and institution)and 20 indicators has been devised to quantify USR.The analytical hierarchy process(AHP)is utilized to compute the weights of the criteria,dimensions,and indicators in the urban seismic resilience assessment(USRA)indicator system.When the necessary data for a city are obtainable,the seismic resilience of that city can be assessed using this framework.To illustrate the proposed methodology,a moderate-sized city in China was selected as a case study.The assessment results indicate a high level of USR,suggesting that the city possesses strong capabilities to withstand and recover from potential future earthquakes.

Propagating subduction initiation of the Caroline Plate at the Mussau Trench

New seismic imaging from the Mussau Trench confirms that,under horizontal compression on an oceanic plate boundary,it is within the young and weak oceanic plate that a trench will develop,and it is the young plate,not so long after its birth,that starts to subduct toward the old plate.The Mesozoic Pacific Plate cannot easily bend,under the joint horizontal compression and vertical gravity pull,even with a pre-existing weak zone in place and with a large age offset across the plate boundary.The bending of the Caroline Plate near the northern end of the Mussau Trench started only after a long-time span of trench migration,and/or after a prolonged transition from initial compression to trench development.Highly contrasting trench deformation and sedimentary accretion between two parallel seismic sections support an evident migration of underthrusting or significant longitudinal heterogeneity along the trench.The swift transition from underthrusting to non-thrusting can be explained by a counter-clockwise rotation of the Caroline Plate.That miniature accretionary wedges develop even before the subduction initiates imply strong compression and uplifting before the underthrusting can kick-start.Rotation of the Caroline Plate have been halted as the Mussau Trench is seismically rather quiet and the Lyra Trough to the east shows relaxational extension.

Gradient‑Layered MXene/Hollow Lignin Nanospheres Architecture Design for Flexible and Stretchable Supercapacitors

With the rapid development of flexible wearable electronics,the demand for stretchable energy storage devices has surged.In this work,a novel gradient-layered architecture was design based on single-pore hollow lignin nanospheres(HLNPs)-intercalated two-dimensional transition metal carbide(Ti_(3)C_(2)T_(x) MXene)for fabricating highly stretchable and durable supercapacitors.By depositing and inserting HLNPs in the MXene layers with a bottom-up decreasing gradient,a multilayered porous MXene structure with smooth ion channels was constructed by reducing the overstacking of MXene lamella.Moreover,the micro-chamber architecture of thin-walled lignin nanospheres effectively extended the contact area between lignin and MXene to improve ion and electron accessibility,thus better utilizing the pseudocapacitive property of lignin.All these strategies effectively enhanced the capacitive performance of the electrodes.In addition,HLNPs,which acted as a protective phase for MXene layer,enhanced mechanical properties of the wrinkled stretchable electrodes by releasing stress through slip and deformation during the stretch-release cycling and greatly improved the structural integrity and capacitive stability of the electrodes.Flexible electrodes and symmetric flexible all-solid-state supercapacitors capable of enduring 600%uniaxial tensile strain were developed with high specific capacitances of 1273 mF cm^(−2)(241 F g^(−1))and 514 mF cm^(−2)(95 F g^(−1)),respectively.Moreover,their capacitances were well preserved after 1000 times of 600%stretch-release cycling.This study showcased new possibilities of incorporating biobased lignin nanospheres in energy storage devices to fabricate stretchable devices leveraging synergies among various two-dimensional nanomaterials.

Smart Cellulose‑Based Janus Fabrics with Switchable Liquid Transportation for Personal Moisture and Thermal Management

The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human comfort.However,the development of smart and dynamic fabrics capable of managing personal moisture/thermal comfort in response to changing external environments remains a challenge.Herein,a smart cellulose-based Janus fabric was designed to dynamically manage personal moisture/heat.The cotton fabric was grafted with N-isopropylacrylamide to construct a temperature-stimulated transport channel.Subsequently,hydrophobic ethyl cellulose and hydrophilic cellulose nanofiber were sprayed on the bottom and top sides of the fabric to obtain wettability gradient.The fabric exhibits anti-gravity directional liquid transportation from hydrophobic side to hydrophilic side,and can dynamically and continuously control the transportation time in a wide range of 3–66 s as the temperature increases from 10 to 40℃.This smart fabric can quickly dissipate heat at high temperatures,while at low temperatures,it can slow down the heat dissipation rate and prevent the human from becoming too cold.In addition,the fabric has UV shielding and photodynamic antibacterial properties through depositing graphitic carbon nitride nanosheets on the hydrophilic side.This smart fabric offers an innovative approach to maximizing personal comfort in environments with significant temperature variations.

Topology Data Analysis-Based Error Detection for Semantic Image Transmission with Incremental Knowledge-Based HARQ

Semantic communication(SemCom)aims to achieve high-fidelity information delivery under low communication consumption by only guaranteeing semantic accuracy.Nevertheless,semantic communication still suffers from unexpected channel volatility and thus developing a re-transmission mechanism(e.g.,hybrid automatic repeat request[HARQ])becomes indispensable.In that regard,instead of discarding previously transmitted information,the incremental knowledge-based HARQ(IK-HARQ)is deemed as a more effective mechanism that could sufficiently utilize the information semantics.However,considering the possible existence of semantic ambiguity in image transmission,a simple bit-level cyclic redundancy check(CRC)might compromise the performance of IK-HARQ.Therefore,there emerges a strong incentive to revolutionize the CRC mechanism,thus more effectively reaping the benefits of both SemCom and HARQ.In this paper,built on top of swin transformer-based joint source-channel coding(JSCC)and IK-HARQ,we propose a semantic image transmission framework SC-TDA-HARQ.In particular,different from the conventional CRC,we introduce a topological data analysis(TDA)-based error detection method,which capably digs out the inner topological and geometric information of images,to capture semantic information and determine the necessity for re-transmission.Extensive numerical results validate the effectiveness and efficiency of the proposed SC-TDA-HARQ framework,especially under the limited bandwidth condition,and manifest the superiority of TDA-based error detection method in image transmission.

Designing Electronic Structures of Multiscale Helical Converters for Tailored Ultrabroad Electromagnetic Absorption

Atomic-scale doping strategies and structure design play pivotal roles in tailoring the electronic structure and physicochemical property of electromagnetic wave absorption(EMWA)materials.However,the relationship between configuration and electromagnetic(EM)loss mechanism has remained elusive.Herein,drawing inspiration from the DNA transcription process,we report the successful synthesis of novel in situ Mn/N co-doped helical carbon nanotubes with ultrabroad EMWA capability.Theoretical calculation and EM simulation confirm that the orbital coupling and spin polarization of the Mn–N4–C configuration,along with cross polarization generated by the helical structure,endow the helical converters with enhanced EM loss.As a result,HMC-8 demonstrates outstanding EMWA performance,achieving a minimum reflection loss of−63.13 dB at an ultralow thickness of 1.29 mm.Through precise tuning of the graphite domain size,HMC-7 achieves an effective absorption bandwidth(EAB)of 6.08 GHz at 2.02 mm thickness.Furthermore,constructing macroscale gradient metamaterials enables an ultrabroadband EAB of 12.16 GHz at a thickness of only 5.00 mm,with the maximum radar cross section reduction value reaching 36.4 dB m2.This innovative approach not only advances the understanding of metal–nonmetal co-doping but also realizes broadband EMWA,thus contributing to the development of EMWA mechanisms and applications.

Neurotransmitter-mediated artificial synapses based on organic electrochemical transistors for future biomimic and bioinspired neuromorphic systems

Organic electrochemical transistors have emerged as a solution for artificial synapses that mimic the neural functions of the brain structure,holding great potentials to break the bottleneck of von Neumann architectures.However,current artificial synapses rely primarily on electrical signals,and little attention has been paid to the vital role of neurotransmitter-mediated artificial synapses.Dopamine is a key neurotransmitter associated with emotion regulation and cognitive processes that needs to be monitored in real time to advance the development of disease diagnostics and neuroscience.To provide insights into the development of artificial synapses with neurotransmitter involvement,this review proposes three steps towards future biomimic and bioinspired neuromorphic systems.We first summarize OECT-based dopamine detection devices,and then review advances in neurotransmitter-mediated artificial synapses and resultant advanced neuromorphic systems.Finally,by exploring the challenges and opportunities related to such neuromorphic systems,we provide a perspective on the future development of biomimetic and bioinspired neuromorphic systems.

Lycium barbarum polysaccharide inhibits retinal neovascularization and inflammation in vitro and in vivo

AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N2),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.

Movement analysis in the diagnosis and management of Parkinson’s disease

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall phenotype.Clinically,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses inexorably.New biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).