Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

A Model of Grand Unified Theory: Suggested Solution for CP-Violation Using Ideas of Phase Paths

This study demonstrates that beyond standard model (BSM) cosmic fundamental interactions—weak, strong, and electromagnetic forces—can be unified through a common basis of representation. This unification allows for the derivation of the fine structure constant with running points of α(t) ≈ 1/(136.9038) at high energy scales, based on electroweak interactions. Through the application of the Ising model, the running point of the elementary charge e at high energy scales is determined, and Coulomb’s law is actually derived from the Yukawa potential. Theoretically, based on S. Weinberg’s electroweak interaction theory, this study unifies the strong and electromagnetic forces by representing them with rYuka, and further advances the reconstruction of the SU(3)C×SU(1)L×U(1)EMframework on the basis of electroweak interaction concepts. In fact, the cosmic fundamental forces can interchange at the mass gap, defined as the Yukawa turning phase at rYuka ≃1.9404 fm, with the SU(3)Diag structural constant fijk on glueballs calculated, estimating a spectrum mass gap of ∆0 > 0.

Evaluating the role of large language models in inflammatory bowel disease patient information

This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.

Solving the Olbers’s Paradox, Explaining the “Red-Shift”, and Challenging the Relativities by “Sun Matters Theory” and “Sun Model of Universe”, an Evolution of the Einstein’s Static Universe Model

Olbers’s paradox, known as the dark night paradox, is an argument in astrophysics that the darkness of the night sky conflicts with the assumption of an infinite and eternal static universe. Big-Bang theory was used to partially explain this paradox, while introducing new problems. Hereby, we propose a better theory, named Sun Matters Theory, to explain this paradox. Moreover, this unique theory supports and extended the Einstein’s static universe model proposed by Albert Einstein in 1917. Further, we proposed our new universe model, “Sun Model of Universe”. Based on the new model and novel theory, we generated innovative field equation by upgrading Einstein’s Field Equation through adding back the cosmological constant, introducing a new variable and modifying the gravitationally-related concepts. According to the Sun Model of Universe, the dark matter and dark energy comprise the so-called “Sun Matters”. The observed phenomenon like the red shift is explained as due to the interaction of ordinary light with Sun Matters leading to its energy and frequency decrease. In Sun Model, our big universe consists of many universes with ordinary matter at the core mixed and surrounded with the Sun Matters. In those universes, the laws of physics may be completely or partially different from that of our ordinary universe with parallel civilizations. The darkness of night can be easily explained as resulting from the interaction of light with the Sun Matters leading to the sharp decrease in the light intensity. Sun Matters also scatter the light from a star, which makes it shining as observed by Hubble. Further, there is a kind of Sun Matters named “Sun Waters”, surrounding every starts. When lights pass by the sun, the Sun Waters deflect the lights to bend the light path. According to the Sun Model, it is the light bent not the space bent that was proposed in the theory of relativities.

Hubble Tension Explanation from This Cosmological Model AΛΩ (Slow Bang Model, SB)

In this article we present a model of Hubble-Lemaître law using the notions of a transmitter (galaxy) and a receiver (MW) coupled to a model of the universe (Slow Bang Model, SB), based on a quantum approach of the evolution of space-time as well as an equation of state that retains all the infinitesimal terms. We find an explanation of the Hubble tension H0. Indeed, we have seen that this constant depends on the transceiver pair which can vary from the lowest observable value, from photons of the CMB (theoretical [km/s/Mpc]) to increasingly higher values depending on the earlier origin of the formation of the observed galaxy or cluster (ETG ~0.3 [Gy], ~74 [km/s/Mpc]). We have produced a theoretical table of the values of the constant according to the possible pairs of transmitter/receiver in the case where these galaxies follow the Hubble flow without large disturbance. The calculated theoretical values of the constant are in the order of magnitude of all values mentioned in past studies. Subsequently, we applied the models to 9 galaxies and COMA cluster and found that the models predict acceptable values of their distances and Hubble constant since these galaxies mainly follow the Hubble flow rather than the effects of a galaxy cluster or a group of clusters. In conclusion, we affirm that this Hubble tension does not really exist and it is rather the understanding of the meaning of this constant that is questioned.

A Biogas Production Model from the Combination of Pig Manure and Cow Dung in N’Zérékoré City, Republic of Guine

This present research work focuses on the valorization of pig droppings for production of biogas in mono digestion and co-digestion with proportions of cow dung from the urban commune of N’Zérékoré. It was carried out in December 2020 in the Physics laboratory of the University of N’Zérékoré. The anaerobic digestion process took 25 days in an almost constant ambient temperature of 25˚C. Five digesters were loaded on 12/06/2020, two of which with 1 kg of pig dung and 1 kg of cow dung both in mono-digestion. The 3 other digesters in co-digestion with different proportions of pig manure and cow dung. The substrate in each digester is diluted in 2 liters of water, with a proportion of (1/2). The main results obtained are: 1) the evolution of the temperature and pH during digestion process, 2) the average biogas productions 0.61 liters for (D1);1.20 liter for (D2);1.65 liter for (D3);1.51 liter for (D4) and 1.31 liter for (D5). The cumulative amounts of biogas are respectively: D1 (7.95 liters), D2 (15.60 liters), D3 (21.50 liters), D4 (19.65 liters) and D5 (17.05 liters). The total cumulative production is 81.75 liters at the end of the process. The originality of this research work is that the proposed model examines the relation between the daily biogas production and the variation of temperature, pH and pressure. The combustibility test showed the biogas produced during the first week was no combustible (contains less than 50% methane). Combustion started from the biogas produced from the 15th day and it is from the 20th day that a significant amount of stable yellow/blue flame was observed. The results of this study show the combination of pig manure and cow dung presents advantages for optimal biogas production.

Analysis of Porter’s Five Forces Competitive Model in China’s Property Rights Trading Market

In recent years,China’s property rights trading market has been extremely competitive,but there are also new contradictions and challenges.This paper aims to analyze the external and internal competitive market of the property rights market through Porter’s five forces competition model,then find out the problems and defects in the development,thereby promoting the better development and progress of China’s property rights trading market.

R-Factor Analysis of Data Based on Population Models Comprising R- and Q-Factors Leads to Biased Loading Estimates

Effects of performing an R-factor analysis of observed variables based on population models comprising R- and Q-factors were investigated. Although R-factor analysis of data based on a population model comprising R- and Q-factors is possible, this may lead to model error. Accordingly, loading estimates resulting from R-factor analysis of sample data drawn from a population based on a combination of R- and Q-factors will be biased. It was shown in a simulation study that a large amount of Q-factor variance induces an increase in the variation of R-factor loading estimates beyond the chance level. Tests of the multivariate kurtosis of observed variables are proposed as an indicator of possible Q-factor variance in observed variables as a prerequisite for R-factor analysis.

深水采油树Spring-Seal密封圈接触模型构建与实验测试

为提高深水采油树在高压、高温、低温等工况下长时间工作的稳定性,对采油树密封圈进行重新设计,提出Spring-Seal密封圈(以下简称S密封圈);基于赫兹接触理论、填料密封接触理论,重新构建S密封圈接触力学模型;建立有限元仿真分析模型,分析不同条件下S密封圈的密封性能,同时验证新建接触模型的合理性;利用实验测试S密封圈的实际密封效果。研究结果表明:S密封圈在高压、高温、低温等工况下能够长时间稳定工作且密封性能良好。研究结果可为S密封圈的接触研究及工程运用提供理论参考。

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

A bibliometric analysis using machine learning to track paradigm shifts and analytical advances in forest ecology and forestry journal publications from 2010 to 2022

Forest habitats are critical for biodiversity,ecosystem services,human livelihoods,and well-being.Capacity to conduct theoretical and applied forest ecology research addressing direct(e.g.,deforestation)and indirect(e.g.,climate change)anthropogenic pressures has benefited considerably from new field-and statistical-techniques.We used machine learning and bibliometric structural topic modelling to identify 20 latent topics comprising four principal fields from a corpus of 16,952 forest ecology/forestry articles published in eight ecology and five forestry journals between 2010 and 2022.Articles published per year increased from 820 in 2010 to 2,354 in 2021,shifting toward more applied topics.Publications from China and some countries in North America and Europe dominated,with relatively fewer articles from some countries in West and Central Africa and West Asia,despite globally important forest resources.Most study sites were in some countries in North America,Central Asia,and South America,and Australia.Articles utilizing R statistical software predominated,increasing from 29.5%in 2010 to 71.4%in 2022.The most frequently used packages included lme4,vegan,nlme,MuMIn,ggplot2,car,MASS,mgcv,multcomp and raster.R was more often used in forest ecology than applied forestry articles.R software offers advantages in script and workflow-sharing compared to other statistical packages.Our findings demonstrate that the disciplines of forest ecology/forestry are expanding both in number and scope,aided by more sophisticated statistical tools,to tackle the challenges of redressing forest habitat loss and the socio-economic impacts of deforestation.

Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer’s disease mice

Amyloid beta(Aβ)monomers aggregate to form fibrils and amyloid plaques,which are critical mechanisms in the pathogenesis of Alzheimer’s disease(AD).Given the important role of Aβ1-42 aggregation in plaque formation,leading to brain lesions and cognitive impairment,numerous studies have aimed to reduce Aβaggregation and slow AD progression.The diphenylalanine(FF)sequence is critical for amyloid aggregation,and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings.In this study,we examined the effects of a moderate-intensity rotating magnetic field(RMF)on Aβaggregation and AD pathogenesis.Results indicated that the RMF directly inhibited Aβamyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro.Using the AD mouse model APP/PS1,RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments,including exploration and spatial and non-spatial memory abilities.Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation,attenuated microglial activation,and reduced oxidative stress in the APP/PS1 mouse brain.These findings suggest that RMF holds considerable potential as a non-invasive,high-penetration physical approach for AD treatment.

Elevation transition of aquatic insects closely matches a thermal feature in the Yungas of Northwestern Argentina

Temperature is a key factor that shapes the distribution of organisms.Having knowledge about how species respond to temperature is relevant to devise strategies for addressing the impacts of climate change.Aquatic insects are particularly vulnerable to climate change,yet there is still much to learn about their ecology and distribution.In the Yungas ecoregion of Northwestern Argentina,cold-and warm-adapted species of the orders Ephemeroptera,Plecoptera,and Trichoptera(EPT)are segregated by elevation.We modeled the ecological niche of South American EPT species in this region using available data and projected their potential distribution in geographic space.Species were grouped based on their ecogeographic similarity,and we analyzed their replacement pattern along elevation gradients,focusing on the ecotone where opposing thermal preferences converge.Along this interface,we identified critical points where the combined incidence of cold and warm assemblages maximizes,indicating a significant transition zone.We found that the Montane Cloud Forest holds the interface,with a particularly greater suitability at its lower boundary.The main axis of the interface runs in a N-S direction and falls between 14°C-16°C mean annual isotherms.The probability of a particular location within a basin being classified as part of the interface increases as Kira’s warmth index approaches a score around 150.Understanding the interface is critical for defining the thermal limits of species distribution and designing biomonitoring programs.Changes in the location of thermal constants related to mountainous ecotones may cause vertical displacement of aquatic insects and vegetation communities.We have recognized significant temperature thresholds that serve as indicators of suitability for the interface.As global warming is anticipated to shift these indicators,we suggest using them to monitor the imprints of climate change on mountain ecosystems.

Real-Time Co-optimization of Gear Shifting and Engine Torque for Predictive Cruise Control of Heavy-Duty Trucks

Fuel consumption is one of the main concerns for heavy-duty trucks.Predictive cruise control(PCC)provides an intriguing opportunity to reduce fuel consumption by using the upcoming road information.In this study,a real-time implementable PCC,which simultaneously optimizes engine torque and gear shifting,is proposed for heavy-duty trucks.To minimize fuel consumption,the problem of the PCC is formulated as a nonlinear model predictive control(MPC),in which the upcoming road elevation information is used.Finding the solution of the nonlinear MPC is time consuming;thus,a real-time implementable solver is developed based on Pontryagin’s maximum principle and indirect shooting method.Dynamic programming(DP)algorithm,as a global optimization algorithm,is used as a performance benchmark for the proposed solver.Simulation,hardware-in-the-loop and real-truck experiments are conducted to verify the performance of the proposed controller.The results demonstrate that the MPC-based solution performs nearly as well as the DP-based solution,with less than 1%deviation for testing roads.Moreover,the proposed co-optimization controller is implementable in a real-truck,and the proposed MPC-based PCC algorithm achieves a fuel-saving rate of 7.9%without compromising the truck’s travel time.

Proximity to corridors benefits bird communities in vegetated interrow vineyards in Mendoza, Argentina

Management under ecological schemes and increasing habitat heterogeneity,are essential for enhancing biodiversity in vineyards.Birds provide several contributions to agriculture,for example pest control,recreation and enhancing human mental health,and have intrinsic value.Birds are also ideal model organisms because they are easy to survey,and species respond differently to agricultural land use at different scales.Vegetated borders of crops are key for many species of birds,and distance to the border have been found to be an important factor in vineyard-dominated agroecosystems.We evaluate if there are differences in the bird assemblage,between the interior compared to borders within vineyards,using a hierarchical community occupancy model.We hypoth-esized that occupancy of birds is greater in environments with greater heterogeneity,which in this study was considered to be contributed by the proximity to vegetated corridors.We expected that vineyard borders close to corridors will have higher bird occupancy than the center of the vineyard.The research was conducted in three vineyards with biodiversity-friendly management practices,in Gualtallary,Mendoza,Argentina.Bird surveys were conducted over three breeding seasons from 2018 to 2020.Occupancy and richness of the bird community was more closely associated with the borders adjacent to the corridors than with the interior of the vineyards,as we initially predicted,although the assemblage of birds did not differ much.More than 75%of the registered species consume exclusively or partially invertebrates.Biodiversity-friendly management and ecological schemes,together with vegetated corridors provide multiple benefits for biodiversity conservation.These ap-proaches not only minimize the use of agrochemicals but also prioritize soil cover with spontaneous vegetation,which supports a diverse community of insectivorous bird species,potentially contributing to pest control.

Prospects for Jovian seismology with the Lenghu planetary telescope

Jupiter is one of the top priorities for deep space exploration in China and other countries.The structure of Jupiter’s interior,in particular,is a crucial but still unclear scientific topic.This paper discusses current scientific understanding of Jupiter’s interior by summarizing the history of past and current exploration and data analysis.We review recent space-based and ground-based observation methods and analyze their feasibility.To gain new insight into the internal structure of Jupiter,we propose to study Jupiter’s innards by planetary seismology.Ground-based observation,namely the Jupiter Seismologic Interferometer Polarization Imager(SIPI)in Lenghu,will be developed to obtain the Doppler velocity distribution on the surface of Jupiter and identify oscillation signals.Lenghu has observation conditions that are not only exceptional in China but even in the world,capable of providing novel insight into the interior of Jupiter.This will also be the first study in China of the interior of Jupiter using asteroseismology,which has significant implications for China’s plans to explore Jupiter via spacecraft-mounted instruments.

Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

Gas hydrate saturation from NGHP 02 LWD data in the Mahanadi Basin

During the Indian National Gas Hydrate Program(NGHP)Expedition 02,Logging-while-drilling(LWD)logs were acquired at three sites(NGHP-02-11,NGHP-02-12,and NGHP-02-13)across the Mahanadi Basin in area A.We applied rock physics theory to available sonic velocity logs to know the distribution of gas hydrate at site NGHP-02-11 and NGHP-02-13.Rock physics modeling using sonic velocity at well location shows that gas hydrate is distributed mainly within the depth intervals of 150-265 m and 100 -215 mbsf at site NGHP-02-11 and NGHP-02-13,respectively,with an average saturation of about 4%of the pore space and the maximum concentration of about 40%of the pore space at 250 m depth at site NGHP-02-11,and at site NGHP-02-13 an average saturation of about 2%of the pore space and the maximum concentration of about 20%of the pore space at 246 m depth,as gas hydrate is distributed mainly within 100-246 mbsf at this site.Saturation of gas hydrate estimated from the electrical resistivity method using density derived porosity and electrical resistivity logs from Archie's empirical formula shows high saturation compared to that from the sonic log.However,estimates of hydrate saturation based on sonic P-wave velocity may differ significantly from that based on resistivity,because gas and hydrate have higher resistivity than conductive pore fluid and sonic P-wave velocity shows strong effect on gas hydrate as a small amount of gas reduces the velocity significantly while increasing velocity due to the presence of hydrate.At site NGHP-02-11,gas hydrate saturation is in the range of 15%e30%,in two zones between 150-180 and 245-265 mbsf.Site NGHP-02-012 shows a gas hydrate saturation of 20%e30%in the zone between 100 and 207 mbsf.Site NGHP-02-13 shows a gas hydrate saturation up to 30%in the zone between 215 and 246 mbsf.Combined observations from rock physics modeling and Archie’s approximation show the gas hydrate concentrations are relatively low(<4%of the pore space)at the sites of the Mahanadi Basin in the turbidite channel system.