Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

Tuning the crystallinity of titanium nitride on copper-embedded carbon nanofiber interlayers for accelerated electrochemical kinetics in lithium-sulfur batteries

The development of lithium-sulfur(Li-S)batteries is hindered by the disadvantages of shuttling of polysulfides and the sluggish redox kinetics of the conversion of sulfur species during discharge and charge.Herein,the crystallinities of a titanium nitride(TiN)film on copper-embedded carbon nanofibers(Cu-CNFs)are regulated and the nanofibers are used as interlayers to resolve the aforementioned crucial issues.A low-crystalline TiN-coated Cu-CNF(L-TiN-Cu-CNF)interlayer is compared with its highly crystalline counterpart(H-TiN-Cu-CNFs).It is demonstrated that the L-TiN coating not only strengthens the chemical adsorption toward polysulfides but also greatly accelerates the electrochemical conversion of polysulfides.Due to robust carbon frameworks and enhanced kinetics,impressive highrate performance at 2 C(913 mAh g^(-1)based on sulfur)as well as remarkable cyclic stability up to 300 cycles(626 mAh g^(-1))with capacity retention of 46.5%is realized for L-TiN-Cu-CNF interlayer-configured Li-S batteries.Even under high loading(3.8 mg cm^(-2))of sulfur and relatively lean electrolyte(10μL electrolyte per milligram sulfur)conditions,the Li-S battery equipped with L-TiN-Cu-CNF interlayers delivers a high capacity of 1144 mAh g^(-1)with cathodic capacity of 4.25 mAh cm^(-2)at 0.1 C,providing a potential pathway toward the design of multifunctional interlayers for highly efficient Li-S batteries.

Investigation of Projectile Impact Behaviors of Graphene Aerogel Using Molecular Dynamics Simulations

Graphene aerogel(GA),as a novel solid material,has shown great potential in engineering applications due to its unique mechanical properties.In this study,the mechanical performance of GA under high-velocity projectile impacts is thoroughly investigated using full-atomic molecular dynamics(MD)simulations.The study results show that the porous structure and density are key factors determining the mechanical response of GA under impact loading.Specifically,the impact-induced penetration of the projectile leads to the collapse of the pore structure,causing stretching and subsequent rupture of covalent bonds in graphene sheets.Moreover,the effects of temperature on the mechanical performance of GA have been proven to be minimal,thereby highlighting the mechanical stability of GA over a wide range of temperatures.Finally,the energy absorption density(EAD)and energy absorption efficiency(EAE)metrics are adopted to assess the energy absorption capacity of GA during projectile penetration.The research findings of this work demonstrate the significant potential of GA for energy absorption applications.

Timing and Spectral Analysis of the Black Hole X-Ray Binary MAXI J1803-298 with Insight-HXMT Data

We present a comprehensive analysis of the 2021 outburst of MAXI J1803–298 utilizing observations of the Insight-Hard X-ray Modulation Telescope(Insight-HXMT)spanning from the low hard state to the high soft state.Within the Insight-HXMT data set,compared to the previous work,we identify a more prolonged presence of typeC quasi-periodic oscillations(QPOs)with centroid frequencies ranging from~0.16 to 6.3 Hz,which present correlations with the hardness ratio and the photon index of the Comptonized component.For QPO frequencies less than~2 Hz,the QPO phase lags are hard(photons of 10–19 keV arrive later than those of 1–4 keV),while at higher frequencies,the lags become soft at and above~4 Hz.Furthermore,the spectra in all Insight-HXMT observations consist of a multi-color blackbody component and a Comptonized component,as commonly observed in classical black hole X-ray binaries.We analyze state transitions and the evolution of accretion geometry in this work.The fitted inner disk radius increases abnormally during the low hard state,hypothesized to result from the corona condensing onto the inner disk.Additionally,two significant drops in flux are observed during the soft intermediate state,maybe implying changes in the corona/jet and the disk,respectively.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Robust measurement of orbital angular momentum of a partially coherent vortex beam under amplitude and phase perturbations

The ability to overcome the negative effects,induced by obstacles and turbulent atmosphere,is a core challenge of long-distance information transmission,and it is of great significance in free-space optical communication.The spatial-coherence structure,that characterizes partially coherent fields,provides a new degree of freedom for carrying information.However,due to the influence of the complex transmission environment,the spatial-coherence structure is severely damaged during the propagation path,which undoubtedly limits its ability to transmit information.Here,we realize the robust far-field orbital angular momentum(OAM)transmission and detection by modulating the spatial-coherence structure of a partially coherent vortex beam with the help of the cross-phase.The cross-phase enables the OAM information,quantified by the topological charge,hidden in the spatial-coherence structure can be stably transmitted to the far field and can resist the influence of obstructions and turbulence within the communication link.This is due to the self-reconstruction property of the spatial-coherence structure embedded with the cross-phase.We demonstrate experimentally that the topological charge information can be recognized well by measuring the spatial-coherence structure in the far field,exhibiting a set of distinct and separated dark rings even under amplitude and phase perturbations.Our findings open a door for robust optical signal transmission through the complex environment and may find application in optical communication through a turbulent atmosphere.

Towards medical imaging of drug photoactivation:Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents

In recent years,the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology.One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups(PPGs).To effectively utilize light-activated drugs in future medical applications,physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents.Here,we describe the development and evaluation of magnetic resonance(MR)imaging agents that allow for the detection of light penetration and drug activation in the tissues using non-invasive whole-body magnetic resonance imaging(MRI)and chemical exchange saturation transfer(CEST)-MRI modalities.The approach relies on the use of PPG-protected MR contrast agents,which upon irradiation with light change their imaging signal.A Gadolinium(III)-based MRI contrast agent is presented that undergoes a significant change in relaxivity(25%)upon uncaging,providing a reliable indicator of lightinduced cargo release.Additionally,we introduce the first light-responsive CESTMRI imaging agent,enabling positive signal enhancement(off-to-on)upon light activation,offering a novel approach to visualize the activation of photoactive agents in living tissues.This research provides a proof-of-principle for the noninvasive,whole-body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and cognition.In the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to neurodegeneration.Among these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

MRI-determined fat content of human liver,pancreas and kidney

AIM:To assess and correlate the lipid content of various organs in obese subjects and in persons with a normal body weight.METHODS:Magnetic resonance spectroscopy and a previously validated gradient echo magnetic resonance imaging method with Dixon's two point technique were used in this study to quantify fat in liver,pancreas as well as kidney.RESULTS:In 36 volunteers with body mass index(BMI) ranging from 20.0 to 42.9 kg/m2,the median fat content of liver,pancreas and kidney was 2.3%(interquartile range:0.2%-7.8%),2.7%(1.0%-6.5%) and 0.7%(0.1%-1.4%),respectively.BMI and subcutaneous fat correlated significantly with liver and pancreas fat content.We show for the first time the significant correlation of liver and pancreas fat content in healthy controls(r = 0.43,P < 0.01).These observations are related to body weight as measured by BMI and the amount of subcutaneous fat.Kidney fat content is very low and correlates with none of the other fat depots.CONCLUSION:Renal lipid accumulation,unlike the coupled accumulations of fat in liver and pancreas,is not observed in obese subjects.Unlike suggestions made in previous studies,renal lipid accumulation appears not to be involved in the pathogenesis of renal disease in humans.

Evolving management of colorectal cancer

This article reviews recent advances in surgical techniques and adjuvant therapies for colorectal cancer, including total mesorectal excision, the resection of liver and lung metastasis and advances in chemoradiation and foreshadows some interventions that may lie just beyond the frontier. In particular, little is known about the intracellular and extracellular cascades that may influence colorectal cancer cell adhesion and metastasis. Although the phosphorylation of focal adhesion kinases and focal adhesion associated proteins in response to integrin-mediated cell matrix binding ("outside in integrin signaling") is well described, the stimulation of cell adhesion by intracellular signals activated by pressure prior to adhesion represents a different signal paradigm. However, several studies have suggested that increased pressure and shear stress activate cancer cell adhesion. Further studies of the pathways that regulate integrin-driven cancer cell adhesion may identify ways to disrupt these signals or block integrin-mediated adhesion so that adhesion and eventual metastasis can be prevented in the future.

Status and perspectives of hierarchical porous carbon materials in terms of high-performance lithium-sulfur batteries

Lithium-sulfur(Li-S)batteries,although a promising candidate of next-generation energy storage devices,are hindered by some bottlenecks in their roadmap toward commercialization.The key challenges include solving the issues such as low utilization of active materials,poor cyclic stability,poor rate performance,and unsatisfactory Coulombic efficiency due to the inherent poor electrical and ionic conductivity of sulfur and its discharged products(e.g.,Li2S2 and Li_(2)S),dissolution and migration of polysulfide ions in the electrolyte,unstable solid electrolyte interphase and dendritic growth on an odes,and volume change in both cathodes and anodes.Owing to the high specific surface area,pore volume,low density,good chemical stability,and particularly multimodal pore sizes,hierarchical porous carbon(HPC)mate rials have received considerable attention for circumventing the above pro blems in Li-S batteries.Herein,recent progress made in the synthetic methods and deployment of HPC materials for various components including sulfur cathodes,separators and interlayers,and lithium anodes in Li-S batteries is presented and summarized.More importantly,the correlation between the structures(pore volume,specific surface area,degree of pores,and heteroatom-doping)of HPC and the electrochemical performances of Li-S batteries is elaborated.Finally,a discussion on the challenges and future perspectives associated with HPCs for Li-S batteries is provided.

Methods of computed tomography screening and management of lung cancer in Tianjin: design of a population-based cohort study

Objective: European lung cancer screening studies using computed tomography(CT) have shown that a management protocol based on measuring lung nodule volume and volume doubling time(VDT) is more specific for early lung cancer detection than a diameter-based protocol. However, whether this also applies to a Chinese population is unclear. The aim of this study is to compare the diagnostic performance of a volume-based protocol with a diameter-based protocol for lung cancer detection and optimize the nodule management criteria for a Chinese population.Methods: This study has a population-based, prospective cohort design and includes 4000 participants from the Hexi district of Tianjin, China. Participants will undergo low-dose chest CT at baseline and after 1 year. Initially, detected lung nodules will be evaluated for diameter and managed according to a routine diameter-based protocol(Clinical Practice Guideline in Oncology for Lung Cancer Screening, Version 2.2018). Subsequently, lung nodules will be evaluated for volume and management will be simulated according to a volume-based protocol and VDT(a European lung nodule management protocol). Participants will be followed up for 4 years to evaluate lung cancer incidence and mortality. The primary outcome is the diagnostic performance of the European volume-based protocol compared to diameter-based management regarding lung nodules detected using low-dose CT.Results: The diagnostic performance of volume-and diameter-based management for lung nodules in a Chinese population will be estimated and compared.Conclusions: Through the study, we expect to improve the management of lung nodules and early detection of lung cancer in Chinese populations.

Management of rectal foreign bodies: Description of a new technique and clinical practice guidelines

A number of techniques have been described to remove rectal foreign bodies. In this report, a novel endoscopic technique using a pneumatic dilatation balloon normally used in achalasia patients is presented. In addition, a systematic review of the literature was performed for non-operative methods to remove foreign bodies from the rectum. These results are summarised, presented as a practical at-a- glance overview and a flow chart is offered to guide the clinician in treatment decisions. The design of the flow chart was based on the aims to treat the patient preferably on an outpatient basis with minimally invasive techniques and if possible under conscious sedation rather than general anaesthesia.

Micromanaging cardiac regeneration:Targeted delivery of micro RNAs for cardiac repair and regeneration

The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-ofthe-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on micro RNA-mediated reprogramming. Additionally, we discuss current advances on state-of-theart targeted drug delivery systems that can be employed to deliver these micro RNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in micro RNAbased therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.

Diagnostic yield of small bowel capsule endoscopy depends on the small bowel transit time

AIM： To investigate whether the small bowel transit time （SBTT） influences the diagnostic yield of capsule endoscopy （CE）. METHODS： Six hundred and ninety-one consecutive CE procedures collected in a database were analyzed. SBTT and CE findings were recorded. A running mean for the SBl-I- was calculated and correlated to the diagnostic yield with a Spearman＇s correlation test. Subgroup anal- yses were performed for the various indications for the procedure. RESULTS： There was a positive correlation between the diagnostic yield and SBT1- （Spearman＇s rho 0.58, P 〈 0.01）. Positive correlations between diagnostic yield and SB-FI-were found for the indication obscure gastro- intestinal bleeding （r = 0.54, P 〈 0.01）, for polyposis and carcinoid combined （r = 0.56, P 〈 0.01） and for the other indications （r = 0.90, P 〈0.01）, but not for suspected Crohn＇s disease （r = -0.40） CONCLUSION： The diagnostic yield in small bowel capsule endoscopy is positively correlated with the small bowel transit time. This is true for all indications except for suspected Crohn＇s disease.

A Technological Overview of Biogas Production from Biowaste

The current irrational use of fossil fuels and the impact of greenhouse gases on the environment are driving research into renewable energy production from organic resources and waste. The global energy demand is high, and most of this energy is produced from fossil resources. Recent studies report that anaerobic di- gestion （AD） is an efficient alternative technology that combines biofuel production with sustainable waste management, and various technological trends exist in the biogas industry that enhance the production and quality of biogas. Further investments in AD are expected to meet with increasing success due to the low cost of available feedstocks and the wide range of uses for biogas （i.e., for heating, electricity, and fuel）. Bio- gas production is growing in the European energy market and offers an economical alternative for bioenergy production. The objective of this work is to provide an overview of biogas production from lignocellulosic waste, thus providing information toward crucial issues in the biogas economy.

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.

Performance of the Montreal classification for inflammatory bowel diseases

AIM: To validate the Montreal classification system for Crohn&#x02019;s disease (CD) and ulcerative colitis (UC) within the Netherlands.

Assessment of Human Impacts on Vegetation in Built-up Areas in China Based on AVHRR,MODIS and DMSP_OLS Nighttime Light Data,1992–2010

Since the reform and opening-up program started in 1978,the level of urbanization has increased rapidly in China.Rapid urban expansion and restructuring have had significant impacts on the ecological environment especially within built-up areas.In this study,ArcGIS 10,ENVI 4.5,and Visual FoxPro 6.0 were used to analyze the human impacts on vegetation in the built-up areas of 656Chinese cities from 1992 to 2010.Firstly,an existing algorithm was refined to extract the boundaries of the built-up areas based on the Defense Meteorological Satellite Program Operational Linescan System(DMSP_OLS)nighttime light data.This improved algorithm has the advantages of high accuracy and speed.Secondly,a mathematical model(Human impacts(HI))was constructed to measure the impacts of human factors on vegetation during rapid urbanization based on Advanced Very High Resolution Radiometer(AVHRR)Normalized Difference Vegetation Index(NDVI)and Moderate Resolution Imaging Spectroradiometer(MODIS)NDVI.HI values greater than zero indicate relatively beneficial effects while values less than zero indicate proportionally adverse effects.The results were analyzed from four aspects:the size of cities(metropolises,large cities,medium-sized cities,and small cities),large regions(the eastern,central,western,and northeastern China),administrative divisions of China(provinces,autonomous regions,and municipalities)and vegetation zones(humid and semi-humid forest zone,semi-arid steppe zone,and arid desert zone).Finally,we discussed how human factors impacted on vegetation changes in the built-up areas.We found that urban planning policies and developmental stages impacted on vegetation changes in the built-up areas.The negative human impacts followed an inverted′U′shape,first rising and then falling with increase of urban scales.China′s national policies,social and economic development affected vegetation changes in the built-up areas.The findings can provide a scientific basis for municipal planning departments,a decision-making reference for government,and scientific guidance for sustainable development in China.

Clinical characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital

Objectives:To evaluate the characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital.Methods:Patients with pulmonary nodules 4–25 mm in diameter detected via computed tomography(CT)in 2013 were consecutively included.The analysis was restricted to patients with a histological nodule diagnosis or a 2-year follow-up period without nodule growth confirming benign disease.Patient information was collected from hospital records.Results:Among the 314 nodules examined in 299 patients,212(67.5%)nodules in 206(68.9%)patients were malignant.Compared to benign nodules,malignant nodules were larger(18.0 mm vs.12.5 mm,P<0.001),more often partly solid(16.0%vs.4.7%,P<0.001)and more often spiculated(72.2%vs.41.2%,P<0.001),with higher density in contrast-enhanced CT(67.0 HU vs.57.5 HU,P=0.015).Final diagnosis was based on surgery in 232 out of 314(73.9%)nodules,166 of which were identified as malignant[30(18.1%)stage III or IV]and 66 as benign.In 36 nodules(11.5%),diagnosis was confirmed by biopsy and the remainder verified based on stability of nodule size at follow-up imaging(n=46,14.6%).Among 65 nodules subjected to gene(EGFR)mutation analyses,28(43.1%)cases(EGFR19 n=13;EGFR21 n=15)were identified as EGFR mutant and 37(56.9%)as EGFR wild-type.Prior to surgery,the majority of patients[n=194(83.6%)]received a contrast-enhanced CT scan for staging of both malignant[n=140(84.3%)]and benign[n=54(81.8%)]nodules.Usage of positron emission tomography(PET)-CT was relatively uncommon[n=38(16.4%)].Conclusions:CT-derived nodule assessment assists in diagnosis of small to intermediate-sized malignant pulmonary nodules.Currently,contrast-enhanced CT is commonly used as the sole diagnostic confirmation technique for pre-surgical staging,often resulting in surgery for late-stage disease and unnecessary surgery in cases of benign nodules.