Resident immune responses to spinal cord injury:role of astrocytes and microglia

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 years.As proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple seasons.Such differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular damage.The present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged darkness.As chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our hypotheses.We predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to annuals.Chlorophyll levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using spectrophotometry.While chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as predicted.When plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,chlorophyll resynthesis rates did not consistently differ between annuals and perennials,though they tended to be higher in the latter,as predicted.Overall,our study illuminates that evolutionary transitions between life history strategies in plants have been accompanied by physiological modifications to chlorophyll dynamics that permit perennial species to better maintain chlorophyll levels—and thus photosynthetic energy acquisition-in the face of exogenous stressors,which likely underlies their capacity to survive for multiple growing seasons.Future studies should explore whether other key biomolecules(e.g.,proteins,DNA)are also better maintained in perennial plants,especially in the face of exogenous stress.

Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

Effect of Artificial Electric Field Surface by Wave-Driven Triboelectricity on Anti-Bioadhesion for Riser Protection

Biofouling has been a persistent problem in marine riser system, resulting in energy waste and equipment damage. Inthis study, a kind of water wave-driven contact-mode flexible triboelectric nanogeneration has been prepared byusing graphene-doped PDMS as dielectric friction material. When the graphene content is 2%, the average outputvoltage can reach 46 V under the contact frequency 10 Hz. The flexible triboelectric nanogeneration encapsulationmodule is impinged by water waves to generate alternating microelectric field on the riser surface and destroy theadhesion conditions of microorganisms during the biofilm stage. In the biofouling experiments at different stages, thebiofouling area of the platymonas subcordiformis has been reduced by 53%, 62% and 61%. It provides a new ideafor effective treatment of biofouling of mussels, oysters and barnacles attached to risers.

Use of endoscopic ultrasound-guided gallbladder drainage as a rescue approach in cases of unsuccessful biliary drainage

This narrative review provides an overview of the utilization of endoscopic ultrasound-guided gallbladder drainage(EUS-GBD)as a salvage approach in cases of unsuccessful conventional management.EUS-GBD is a minimally invasive and effective technique for drainage in patients with acute cholecystitis with high risk of surgery.The procedure has demonstrated impressive technical and clinical success rates with low rates of adverse events,making it a safe and effective option for appropriate candidates.Furthermore,EUS-GBD can also serve as a rescue option for patients who have failed endoscopic retrograde cholangiopancreatography or EUS biliary drainage for relief of jaundice in malignant biliary stricture.However,patient selection is critical for the success of EUS-GBD,and proper patient selection and risk assessment are important to ensure the safety and efficacy of the procedure.As the field continues to evolve and mature,ongoing research will further refine our understanding of the benefits and limitations of EUS-GBD,ultimately leading to improved outcomes for patients.

Effects of fracture evolution and non-Darcy flow on the thermal performance of enhanced geothermal system in 3D complex fractured rock

In fractured geothermal reservoirs,the fracture networks and internal fluid flow behaviors can significantly impact the thermal performance.In this study,we proposed a non-Darcy rough discrete fracture network(NR-DFN)model that can simultaneously consider the fracture evolution and non-Darcy flow dynamics in studying the thermo-hydro-mechanical(THM)coupling processes for heat extraction in geothermal reservoir.We further employed the model on the Habanero enhanced geothermal systems(EGS)project located in Australia.First,our findings illustrate a clear spatial-temporal variation in the thermal stress and pressure perturbations,as well as uneven spatial distribution of shear failure in 3D fracture networks.Activated shear failure is mainly concentrated in the first fracture cluster.Secondly,channeling flow have also been observed in DFNs during heat extraction and are further intensified by the expansion of fractures driven by thermal stresses.Moreover,the combined effect of non-Darcy flow and fracture evolution triggers a rapid decline in the resulting heat rate and temperature.The NR-DFN model framework and the Habanero EGS's results illustrate the importance of both fracture evolution and non-Darcy flow on the efficiency of EGS production and have the potential to promote the development of more sustainable and efficient EGS operations for stakeholders.

Disorders of potassium homeostasis after kidney transplantation

Disturbances of potassium balance are often encountered when managing kidney transplant recipients(KTR).Both hyperkalemia and hypokalemia may present either as medical emergencies or chronic outpatient abnormalities.Despite the high incidence of hyperkalemia and its potential life-threatening implications,consensus on its management in KTR is lacking.Hypokalemia in KTR is also well-described,although it is given less attention by clinicians compared to hyper-kalemia.This article discusses the etiology,pathophysiology and management of both types of potassium disorders in KTR.Once any emergent situation has been corrected,treatment approaches include correcting insulin deficiency if present,adjusting non-immunosuppressive and immunosuppressive medications,elimi-nating or supplementing potassium as needed,and dietary counselling.Although commonly of multifactorial etiology,ascertaining the specific cause in a particular patient will help guide successful management.Monitoring KTR through regular laboratory testing is essential to detect serious disturbances in potassium balance since patients are often asymptomatic.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces

Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.

Effect of roughness on the shear behavior of rock joints subjected to impact loading

The shear behavior is regarded as the dominant property of rock joints and is dramatically affected by the joint surface roughness.To date,the effect of surface roughness on the shear behavior of rock joints under static or cyclic loading conditions has been extensively studied,but such effect under impact loading conditions keeps unclear.To address this issue,a series of impact shear tests was performed using a novel-designed dynamic experimental system combined with the digital image correlation(DIC)technique.The dynamic shear strength,deformability and failure mode of the jointed specimens with various joint roughness coefficients(JRC)are comprehensively analyzed.Results show that the shear strength and shear displacement characteristics of the rock joint under the impact loading keep consistent with those under static loading conditions.However,the temporal variations of shear stress,slip displacement and normal displacement under the impact loading conditions show obviously different behaviors.An elastic rebound of the slip displacement occurs during the impact shearing and its value increases with increasing joint roughness.Two identifiable stages(i.e.compression and dilation)are observed in the normal displacement curves for the rougher rock joints,whereas the joints with small roughness only manifest normal compression displacement.Besides,as the roughness increases,the maximum compression tends to decrease,while the maximum dilation gradually increases.More-over,the microstructural analysis based on scanning electron microscope(SEM)suggests that the roughness significantly affects the characteristics of the shear fractured zone enclosing the joint surface.

Microscopic damage evolution of anisotropic rocks under indirect tensile conditions: Insights from acoustic emission and digital image correlation techniques

The anisotropy induced by rock bedding structures is usually manifested in the mechanical behaviors and failure modes of rocks.Brazilian tests are conducted for seven groups of shale specimens featuring different bedding angles. Acoustic emission (AE) and digital image correlation (DIC) technologies are used to monitor the in-situ failure of the specimens. Furthermore, the crack morphology of damaged samples is observed through scanning electron microscopy (SEM). Results reveal the structural dependence on the tensile mechanical behavior of shales. The shale disk exhibits compression in the early stage of the experiment with varying locations and durations. The location of the compression area moves downward and gradually disappears when the bedding angle increases. The macroscopic failure is well characterized by AE event location results, and the dominant frequency distribution is related to the bedding angle. The b-value is found to be stress-dependent.The crack turning angle between layers and the number of cracks crossing the bedding both increase with the bedding angle, indicating competition between crack propagations. SEM results revealed that the failure modes of the samples can be classified into three types:tensile failure along beddings with shear failure of the matrix, ladder shear failure along beddings with tensile failure of the matrix, and shear failure along multiple beddings with tensile failure of the matrix.

On the calibration and verification of Voronoi-based discontinuous deformation analysis for modeling rock fracture

Since its introduction,discontinuous deformation analysis(DDA)has been widely used in different areas of rock mechanics.By dividing large blocks into subblocks and introducing artificial joints,DDA can be applied to rock fracture simulation.However,parameter calibration,a fundamental issue in discontinuum methods,has not received enough attention in DDA.In this study,the parameter calibration of DDA for intact rock is carefully studied.To this end,a subblock DDA with Voronoi tessellation is presented first.Then,a modified contact constitutive law is introduced,in which the tensile and shear meso-strengths are modified to be independent of the bond lengths.This improvement can prevent the unjustified preferential failure of short edges.A method for imposing confining pressure is also introduced.Thereafter,sensitivity analysis is performed to investigate the influence of the calculated parameters and meso-parameters on the mechanical properties of modeled rock.Based on the sensitivity analysis,a unified calibration procedure is suggested for both cases with and without confining pressure.Finally,the calibration procedure is applied to two examples,including a biaxial compression test.The results show that the proposed Voronoi-based DDA can simulate rock fracture with and without confining pressure very well after careful parameter calibration.

Use of metaphors when treating unexplained medical symptoms

The words one chooses to describe personal pain mirror current usage, but may also hold echoes of an individual’s lived experience. They may provide clues to the origin of physical symptoms that are medically hard to explain. The aim of this commentary is to propose, on the basis of the available literature, that verbal metaphors can prove effective in the psychotherapy of such conditions. I provide a case history of a 45 year old woman referred to psychiatry because of extreme ‘burning’ pain in her mouth and tongue. She had been to numerous doctors, had undergone a variety of tests, had tried many medical treatments, and had been prescribed a number of different pharmaceutical agents. She had changed her diet, done her daily dental mouth exercises, drunk a lot of water, but the burning continued and interfered, with her job(she was a teacher), her friendships, and her everyday life. This made her angry and recalcitrant to therapy, but the metaphor ‘burning with rage,’ as applicable to her pain, worked to establish a good alliance that led to a decrease of symptoms. Burning Mouth Syndrome is a medically unexplained condition of complex etiology that psychotherapy alone cannot reverse. The literature bears out, however, that the use of metaphors can help to open avenues of psychological exploration that accelerate adaptation to pain and improve quality life.

Applications and safety of gold nanoparticles as therapeutic devices in clinical trials

Use of gold nanoparticles(GNPs)in medicine is an emerging field of translational research with vast clinical implications and exciting therapeutic potential.However,the safety of using GNPs in human subjects is an important question that remains unanswered.This study reviews over 20 clinical trials focused on GNP safety and aims to summarize all the clinical studies,completed and ongoing,to identify whether GNPs are safe to use in humans as a therapeutic platform.In these studies,GNPs were implemented as drug delivery devices,for photothermal therapy,and utilized for their intrinsic therapeutic effects by various routes of delivery.These studies revealed no major safety concerns with the use of GNPs;however,the number of trials and total patient number remains limited.Multi-dose,multicenter blinded trials are required to deepen our understanding of the use of GNPs in clinical settings to facilitate translation of this novel,multifaceted therapeutic device.Expanding clinical trials will require collaboration between clinicians,scientists,and biotechnology companies.

Correction of dynamic Brazilian disc tensile strength of rocks under preloading conditions considering the overload phenomenon and invoking the Griffith criterion

Dynamic tensile failure is a common phenomenon in deep rock practices,and thus accurately evaluating the dynamic tensile responses of rocks under triaxial pressures is of great significance.The Brazilian disc(BD)test is the suggested method by the International Society for Rock Mechanics and Rock Engineering(ISRM)for measuring both the static and dynamic tensile strengths of rock-like materials.However,due to the overload phenomenon and the complex preloading conditions,the dynamic tensile strengths of rocks measured by the BD tests tend to be overestimated.To address this issue,the dynamic BD tensile strength(BTS)of Fangshan marble(FM)under different preloading conditions were measured through a triaxial split Hopkinson pressure bar(SHPB).The fracture onset in BD specimen was captured through a strain gage around the disc center.The discrepancy between the traditional tensile strength(TTS,determined by the peak load P_(f) of the BD specimen)and the nominal tensile strength(NTS,obtained from the load P_(i) when the diametral fracture commences in the tested BD specimen)was applied to quantitatively evaluating the overload phenomenon.The Griffith criterion was used to rectify the calculation of the tensile stress at the disc center under triaxial stress states.The results demonstrate that the overload ratio(s)increases with the loading rate(σ)and decreases with the hydrostatic pressure(σ_(s)).The TTS corrected by the Griffith criterion is independent of theσ_(s)due to the overload phenomenon,while the NTS corrected by the Griffith criterion is sensitive to both the andσ.Therefore,it is essential to modify the tensile stress in dynamic confined BD tests using both the overload correction and the Griffith criterion rectification to obtain the accurate dynamic BTS of rocks.

Dynamic responses and failure mechanisms of the existing tunnel under transient excavation unloading of an adjacent tunnel

Engineering disasters(e.g.rock slabbing and rockburst)of the tunnel groups induced by the transient excavation of an adjacent tunnel threaten the stability of the existing tunnel,especially for those excavated by using the drill and blast tunneling(D&B).However,the dynamic response and failure mechanism of surrounding rocks of the existing tunnel caused by adjacent transient excavation are not clear due to the difficulty in conducting field tests and laboratory experiments.Therefore,a novel transient unloading experimental system for deep tunnel excavation was proposed in this study.The real stress path and the unloading rate can be reproduced by using this proposed system.The experiments were conducted for observing the dynamic response of the existing tunnel induced by adjacent transient excavation under different lateral pressure coefficients l(?0.4,0.6,0.8,1,1.2,1.4,1.6,1.8)with a polymethyl methacrylate(PMMA)specimen.The propagation of the impact wave and unloading surface wave was detected through the digital image correlation(DIC)analysis.The reflection of the unloading surface wave on the incident side of the existing tunnel(tunnel-E)was observed and analyzed.Moreover,the dynamic characteristics of the stress redistribution,the particle displacement and vibration velocity of surrounding rocks of tunnel-E were analyzed and summarized.In addition,the Mohr-Coulomb(MeC)failure criterion with tension cut-off was adopted to evaluate the stability of the existing tunnel under adjacent transient excavation.The results indicate that the incident side of the existing tunnel under the dynamic disturbance of transient excavation of an adjacent tunnel was more prone to fail,followed by the shadow side and the top/bottom side.

Principles of Nanoparticle Delivery to Solid Tumors

The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site.Nanoparticles provide an essential transport system.We present 5 principles to consider when designing nanoparticles for cancer targeting:(a)Nanoparticles acquire biological identity in vivo,(b)organs compete for nanoparticles in circulation,(c)nanoparticles must enter solid tumors to target tumor components,(d)nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting,and(e)size,shape,surface chemistry,and other physicochemical properties of nanoparticles influence their transport process to the target.This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.

Increased odds of high body mass index in depression with self-reported antidepressant use

To theeditor:The incidence of depression and obesity is on the rise,posing significant public health concerns.While the literature largely supports a positive correlation between depression and body mass index(BMI),I2 earlier studies have suggested an inverse relationship or indicated a lack of association between depression and obesity.

What Is Dentists’ Role in Modulating Environmental and Epigenetic Determinant in Oral Health of Diabetic Patients?

Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start of the deadly disease. As the sixth complication of diabetes, periodontitis is a chronic inflammatory condition that leads directly and indirectly to a severer condition of diabetes via its underlying mechanisms. Interestingly, both diseases are not been fully identified in their bidirectional relationships by researchers. Thus, healthcare agencies must pay appropriate attention. This literature review paper aims to investigate and discuss dentists’ role in modulating environmental and epigenetic determinants in the oral health of diabetic patients based on the bidirectional relationship between these diseases, their prevalence and how treatment of one disease affects the other. Methods: The authors conducted electronic searches in PubMed, Google Scholar, One Search UofT, ScienceDirect, and the National Library of Medicine. The paper also included gray literature from government resources related to the topic. The paper will review the epidemiology, pathogenesis, and epigenetics of both diabetes and periodontal disease and their functions with each other. Results: The literature has consistently shown that diabetes and periodontal disease have responded to the formation and severity of each other. Patients with pre- and diabetes have potentially higher risks of causing periodontal disease and other complications if adequate diagnosis and treatment are not involved timely. The combination of risk factors, including individual, social, environmental, and genetic, play a crucial role in the development of diabetes and the severity of periodontitis. Conclusions: Based on the results, the collaboration between dentists and other healthcare practitioners is inevitable in the overall development of treatment for both diseases. With the proper and updated knowledge, dentists can benefit patients’ overall physical conditions through strategic intervention in diabetes patients.

Bionic Flexible Texture Design Based on Bio-Fouling Suppression Effect for Protection of Marine Structures

Marine equipments such as marine risers and oil pipelines operate in complex underwater environments and are usually attached by animals,plants and microorganisms.The attachment of marine fouling organisms will accelerate the corrosion damage of offshore structure and greatly reduce the service life.Studies have shown that non-smooth bionic surfaces with specific microstructures can inhibit fouling formation.Based on the idea of bionics,this paper proposes a new type of underwater flexible fretting texture,which is a composite material prepared by mixing graphene and silicone rubber,and modified by pulsed laser to construct a hexagonal bionic surface texture.Under the impact of specific water flow,the flexible texture can produce an angular displacement around 8°and a linear displacement in the amplitude range of 165μm,and the inhibition rate of fouling biological diatoms up to 97.5%,which can effectively avoid the occurrence of marine biological fouling.The results provide a new idea for the surface protection of marine structures,which is of great significance for the development of marine industry.