Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

Global research trends and prospects of cellular metabolism in colorectal cancer

BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

Cellular Chemical Field and Cellular Homeostasis

1.Introduction Cell structure and function are controlled by a complex regulatory networking process,in which molecular adaptation and interaction are essential to maintain cellular homeostasis following dynamic multi-omics rules and multi-systematic changes.This complex chemical process is an important mechanism for stabilizing the cell microenvironment.

Current and future research directions in cellular metabolism of colorectal cancer:A bibliometric analysis

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.

Cellular Senescence and SENEX Gene on the Peripheral CD4+CD25+ Treg Cells Enhancement in Elderly

Cellular senescence is a signal transduction process which maintained genomic stability and stopped mammalian cell growth. Furthermore, cellular senescence induces a protective response to a variety of DNA damage. However, this process is also associated with apoptosis, upregulated secretion of inflammatory cytokine, and promoted surrounding tissue damage. When cellular senescence accumulates to a certain extent, it triggers geriatric diseases, such as chronic inflammation, immune senescence-associated tumors and incontrollable infections. Cellular senescence gene SENEX, which was cloned in 2004, has been demonstrated to play a unique gatekeeper function in human endothelial cells when stress-induced pre-mature senescence and apoptosis occurr. The phenomenon that CD4+CD25+ Treg cells accumulated in the aged population has been well studied in recent years. Now Treg accumulation related to immune-pathology has attracted more interest. CD4+CD25+ Treg did not decline and age, but accumulated and suppressed immunoreaction. The enhanced Treg number and function may be associated with stress-induced premature senescence-mediated unique cellular senescence protection mechanisms, and SENEX may play a critical role in this process. In this article, we summarize the cellular senescence and SENEX gene in the accumulation and functional activity of CD4+CD25+ Treg in the elderly.

Advances in micropillar arrays in cellular biomechanics detectionand tissue engineering

Cellular biomechanical features contributed to the occurrence and development of various physiological andpathological phenomena. Micropillar arrays have emerged as an important tool for both the assessment andmanipulation of cellular biomechanical characteristics. This comprehensive review provides an in-depthunderstanding of the fabrication methodologies of micropillar arrays and their applications in deciphering and finetuning cellular biomechanical properties and the innovative experimental platforms including organ-on-a-chip andorganoids-on-a-chip. This review provides novel insights into the potential of micropillar technology, poised toupdate the landscape of stem cell research and tissue engineering.

Simulation of Dynamic Recrystallization in 7075 Aluminum Alloy Using Cellular Automaton

The evolution of microstructure during hot deformation is key to achieving good mechanical properties in aluminum alloys.We have developed a cellular automaton(CA) based model to simulate the microstructural evolution in 7075 aluminum alloy during hot deformation.Isothermal compression tests were conducted to obtain material parameters for 7075 aluminum alloy,leading to the establishment of models for dislocation density,nucleation of recrystallized grains,and grain growth.Integrating these aspects with grain topological deformation,our CA model effectively predicts flow stress,dynamic recrystallization(DRX) volume fraction,and average grain size under diverse deformation conditions.A systematic comparison was made between electron back scattered diffraction(EBSD) maps and CA model simulated under different deformation temperatures(573 to 723 K),strain rates(0.001 to 1 s^(-1)),and strain amounts(30% to 70%).These analyses indicate that large strain,high temperature,and low strain rate facilitate dynamic recrystallization and grain refinement.The results from the CA model show good accuracy and predictive capability,with experimental error within 10%.

Design and mechanical properties analysis of a cellular Waterbomb origami structure

Cellular structures are commonly used to design energy-absorbing structures,and origami structures are becominga prevalent method of cellular structure design.This paper proposes a foldable cellular structure based on theWaterbomb origami pattern.The geometrical configuration of this structure is described.Quasi-static compressiontests of the origami tube cell of this cellular structure are conducted,and load-displacement relationship curvesare obtained.Numerical simulations are carried out to analyze the effects of aspect ratio,folding angle,thicknessand number of layers of origami tubes on initial peak force and specific energy absorption(SEA).Calculationformulas for initial peak force and SEA are obtained by the multiple linear regression method.The degree ofinfluence of each parameter on the mechanical properties of the single-layer tube cell is compared.The resultsshow that the cellular structure exhibits negative stiffness and periodic load-bearing capacity,as well as foldingangle has the most significant effect on the load-bearing and energy-absorbing capacity.By adjusting the designparameters,the stiffness,load-bearing capacity and energy absorption capacity of this cellular structure can beadjusted,which shows the programmable mechanical properties of this cellular structure.The foldability andthe smooth periodic load-bearing capacity give the structure potential for application as an energy-absorbing structure.

Misdiagnosis of synovial sarcoma-cellular myofibroma with SRFRELA gene fusion:A case report

BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.

Resource Allocation in Multi-User Cellular Networks:A Transformer-Based Deep Reinforcement Learning Approach

To meet the communication services with diverse requirements,dynamic resource allocation has shown increasing importance.In this paper,we consider the multi-slot and multi-user resource allocation(MSMU-RA)in a downlink cellular scenario with the aim of maximizing system spectral efficiency while guaranteeing user fairness.We first model the MSMURA problem as a dual-sequence decision-making process,and then solve it by a novel Transformerbased deep reinforcement learning(TDRL)approach.Specifically,the proposed TDRL approach can be achieved based on two aspects:1)To adapt to the dynamic wireless environment,the proximal policy optimization(PPO)algorithm is used to optimize the multi-slot RA strategy.2)To avoid co-channel interference,the Transformer-based PPO algorithm is presented to obtain the optimal multi-user RA scheme by exploring the mapping between user sequence and resource sequence.Experimental results show that:i)the proposed approach outperforms both the traditional and DRL methods in spectral efficiency and user fairness,ii)the proposed algorithm is superior to DRL approaches in terms of convergence speed and generalization performance.

Dynamics analysis and cryptographic implementation of a fractional-order memristive cellular neural network model

Due to the fact that a memristor with memory properties is an ideal electronic component for implementation of the artificial neural synaptic function,a brand-new tristable locally active memristor model is first proposed in this paper.Here,a novel four-dimensional fractional-order memristive cellular neural network(FO-MCNN)model with hidden attractors is constructed to enhance the engineering feasibility of the original CNN model and its performance.Then,its hardware circuit implementation and complicated dynamic properties are investigated on multi-simulation platforms.Subsequently,it is used toward secure communication application scenarios.Taking it as the pseudo-random number generator(PRNG),a new privacy image security scheme is designed based on the adaptive sampling rate compressive sensing(ASR-CS)model.Eventually,the simulation analysis and comparative experiments manifest that the proposed data encryption scheme possesses strong immunity against various security attack models and satisfactory compression performance.

Direct Correlation among Telomere Length, Cellular Aging, and Rejuvenation Effects of Honey Child Powder

Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.

Dynamics of Land Use/Land Cover Considering Ecosystem Services for a Dense-Population Watershed Based on a Hybrid Dual-Subject Agent and Cellular Automaton Modeling Approach

Land use/land cover represents the interactive and comprehensive influences between human activities and natural conditions,leading to potential conflicts among natural and human-related issues as well as among stakeholders.This study introduced economic standards for farmers.A hybrid approach(CA-ABM)of cellular automaton(CA)and an agent-based model(ABM)was developed to effectively deal with social and land-use synergic issues to examine human–environment interactions and projections of land-use conversions for a humid basin in south China.Natural attributes and socioeconomic data were used to analyze land use/land cover and its drivers of change.The major modules of the CA-ABM are initialization,migration,assets,land suitability,and land-use change decisions.Empirical estimates of the factors influencing the urban land-use conversion probability were captured using parameters based on a spatial logistic regression(SLR)model.Simultaneously,multicriteria evaluation(MCE)and Markov models were introduced to obtain empirical estimates of the factors affecting the probability of ecological land conversion.An agent-based CA-SLR-MCE-Markov(ABCSMM)land-use conversion model was proposed to explore the impacts of policies on land-use conversion.This model can reproduce observed land-use patterns and provide links for forest transition and urban expansion to land-use decisions and ecosystem services.The results demonstrated land-use simulations under multi-policy scenarios,revealing the usefulness of the model for normative research on land-use management.

Full-Scale Isogeometric Topology Optimization of Cellular Structures Based on Kirchhoff-Love Shells

Cellular thin-shell structures are widely applied in ultralightweight designs due to their high bearing capacity and strength-to-weight ratio.In this paper,a full-scale isogeometric topology optimization(ITO)method based on Kirchhoff-Love shells for designing cellular tshin-shell structures with excellent damage tolerance ability is proposed.This method utilizes high-order continuous nonuniform rational B-splines(NURBS)as basis functions for Kirchhoff-Love shell elements.The geometric and analysis models of thin shells are unified by isogeometric analysis(IGA)to avoid geometric approximation error and improve computational accuracy.The topological configurations of thin-shell structures are described by constructing the effective density field on the controlmesh.Local volume constraints are imposed in the proximity of each control point to obtain bone-like cellular structures.To facilitate numerical implementation,the p-norm function is used to aggregate local volume constraints into an equivalent global constraint.Several numerical examples are provided to demonstrate the effectiveness of the proposed method.After simulation and comparative analysis,the results indicate that the cellular thin-shell structures optimized by the proposed method exhibit great load-carrying behavior and high damage robustness.

Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

Unveiling the cellular microstructure-property relations in martensitic stainless steel via laser powder bed fusion

Laser powder bed fusion(LPBF)is a widely recognized additive manufacturing technology that can fabricate complex components rapidly through layer-by-layer formation.However,there is a paucity of research on the effect of laser scanning speed on the cellular microstructure and mechanical properties of martensitic stainless steel.This study systematically investigated the influence of laser scanning speed on the cellular microstructure and mechanical properties of a developed Fe11Cr8Ni5Co3Mo martensitic stainless steel produced by LPBF.The results show that increasing the laser scanning speed from 400 to 1000 mm/s does not lead to a noticeable change in the phase fraction,but it reduces the average size of the cellular microstructure from 0.60 to 0.35μm.The scanning speeds of 400 and 1000 mm/s both had adverse effects on performances of sample,resulting in inadequate fusion and keyhole defects respectively.The optimal scanning speed for fabricating samples was determined to be 800 mm/s,which obtained the highest room temperature tensile strength and elongation,with the ultimate tensile strength measured at(1088.3±2.0)MPa and the elongation of(16.76±0.10)%.Furthermore,the mechanism of the evolution of surface morphology,defects,and energy input were clarified,and the relationship between cellular microstructure size and mechanical properties was also established.

A novel method for clustering cellular data to improve classification

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are missing.We recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within clusters.Here we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical testing.These general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical datasets.We demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

Modeling and Performance Analysis of UAV-Aided Millimeter Wave Cellular Networks with Stochastic Geometry

UAV-aided cellular networks,millimeter wave(mm-wave) communications and multi-antenna techniques are viewed as promising components of the solution for beyond-5G(B5G) and even 6G communications.By leveraging the power of stochastic geometry,this paper aims at providing an effective framework for modeling and analyzing a UAV-aided heterogeneous cellular network,where the terrestrial base stations(TBSs) and the UAV base stations(UBSs) coexist,and the UBSs are provided with mm-wave and multi-antenna techniques.By modeling the TBSs as a PPP and the UBSs as a Matern hard-core point process of type Ⅱ(MPH-Ⅱ),approximated but accurate analytical results for the average rate of the typical user of both tiers are derived through an approximation method based on the mean interference-to-signal ratio(MISR) gain.The influence of some relevant parameters is discussed in detail,and some insights into the network deployment and optimization are revealed.Numerical results show that some trade-offs are worthy of being considered,such as the antenna array size,the altitude of the UAVs and the power control factor of the UBSs.

A Hybrid Level Set Optimization Design Method of Functionally Graded Cellular Structures Considering Connectivity

With the continuous advancement in topology optimization and additive manufacturing(AM)technology,the capability to fabricate functionally graded materials and intricate cellular structures with spatially varying microstructures has grown significantly.However,a critical challenge is encountered in the design of these structures–the absence of robust interface connections between adjacent microstructures,potentially resulting in diminished efficiency or macroscopic failure.A Hybrid Level Set Method(HLSM)is proposed,specifically designed to enhance connectivity among non-uniform microstructures,contributing to the design of functionally graded cellular structures.The HLSM introduces a pioneering algorithm for effectively blending heterogeneous microstructure interfaces.Initially,an interpolation algorithm is presented to construct transition microstructures seamlessly connected on both sides.Subsequently,the algorithm enables the morphing of non-uniform unit cells to seamlessly adapt to interconnected adjacent microstructures.The method,seamlessly integrated into a multi-scale topology optimization framework using the level set method,exhibits its efficacy through numerical examples,showcasing its prowess in optimizing 2D and 3D functionally graded materials(FGM)and multi-scale topology optimization.In essence,the pressing issue of interface connections in complex structure design is not only addressed but also a robust methodology is introduced,substantiated by numerical evidence,advancing optimization capabilities in the realm of functionally graded materials and cellular structures.