Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological thresholds.Mild hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate intake.Severe hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left untreated.Individuals with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

Deep eutectic solvents for separation and purification applications in critical metal metallurgy:Recent advances and perspectives

Solvent extraction,a separation and purification technology,is crucial in critical metal metallurgy.Organic solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and flammability,causing a spectrum of hazards to human health and environmental safety.Neoteric solvents have been recognized as potential alternatives to these harmful organic solvents.In the past two decades,several neoteric solvents have been proposed,including ionic liquids(ILs)and deep eutectic solvents(DESs).DESs have gradually become the focus of green solvents owing to several advantages,namely,low toxicity,degradability,and low cost.In this critical review,their classification,formation mechanisms,preparation methods,characterization technologies,and special physicochemical properties based on the most recent advancements in research have been systematically described.Subsequently,the major separation and purification applications of DESs in critical metal metallurgy were comprehensively summarized.Finally,future opportunities and challenges of DESs were explored in the current research area.In conclusion,this review provides valuable insights for improving our overall understanding of DESs,and it holds important potential for expanding separation and purification applications in critical metal metallurgy.

Transient extreme insulin resistance in a critically ill patient:A case report

BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.

Forging an easier path through graduation:Improving the patient transition from paediatric to adult critical care

Adolescence and the journey to adulthood involves exciting opportunities as well as psychosocial stress for young people growing up.These normal experiences are potentially magnified for teenagers living with chronic illness or disability and their families.Advances in care have improved survival for children with a variety of serious chronic medical conditions such that many who may once have died in childhood now survive well into adulthood with ongoing morbidity.For those with highly complex needs,care is often provided at major paediatric hospitals with expertise,specially trained personnel,and resources to support young people and their families for the first decades of life.At the end of adolescence,however,it is generally appropriate and necessary for young adults and their caregivers to transition to the care of clinicians trained in the care of adults at general hospitals.While there are some well-managed models to support this journey of transition,these are often specific to certain conditions and usually do not involve intensive care.Many patients may encounter considerable challenges during this period.Difficulties may include the loss of established therapeutic relationships,a perception of austerity and reduced amenity in facilities oriented to caring for adult patients,and care by clinicians with less experience with more common paediatric conditions.In addition,there is a risk of potential conflict between clinicians and families regarding goals of care in the event of a critical illness when it occurs in a young adult with major disability and long-term health issues.These challenges present genuine opportunities to better understand the transition from paediatric to adult-based care and to improve processes that assist clinicians who support patients and families as they shift between healthcare settings.

Effect of dietary fibre on the gastrointestinal microbiota during critical illness:A scoping review

The systemic effects of gastrointestinal(GI)microbiota in health and during chronic diseases is increasingly recognised.Dietary strategies to modulate the GI microbiota during chronic diseases have demonstrated promise.While changes in dietary intake can rapidly change the GI microbiota,the impact of dietary changes during acute critical illness on the microbiota remain uncertain.Dietary fibre is metabolised by carbohydrate-active enzymes and,in health,can alter GI microbiota.The aim of this scoping review was to describe the effects of dietary fibre supplementation in health and disease states,specifically during critical illness.Randomised controlled trials and prospective cohort studies that include adults(>18 years age)and reported changes to GI microbiota as one of the study outcomes using non-culture methods,were identified.Studies show dietary fibres have an impact on faecal microbiota in health and disease.The fibre,inulin,has a marked and specific effect on increasing the abundance of faecal Bifidobacteria.Short chain fatty acids produced by Bifidobacteria have been shown to be beneficial in other patient populations.Very few trials have evaluated the effect of dietary fibre on the GI microbiota during critical illness.More research is necessary to establish optimal fibre type,doses,duration of intervention in critical illness.

DETERMINING CRITICAL TIME OF ROCK DYNAMIC FRACTURE BY DYNAMIC MOIRE METHOD

An effective Dynamic Moire method was presented to determine the critical time of crack instable propagation in rock dynamic fracture. Two pieces of grating were installed near the notch of Short Rod specimen to form the Moire fringes, then the COD versus time could be monitored from the movement of the Moire fringes, and finally the critical time could be determined from the velocity of COD. This method was also compared with another one.It could be concluded that the critical time determined by Dynamic Moire method corresponds with that of the Transmitted Wave method at the loading rates from 103 to 104 MPa·m(1/2)·S(-1).

面向Critical MTC的无连接传输

关键机器类通信(Critical MTC)对时延和可靠性都有极高的要求。支持海量Critical MTC的终端是一个巨大挑战。提出了一种面向海量Critical MTC终端的无连接传输方案。为了降低时延,提出了基于竞争的无连接单次传输方案;为了实现高可靠性,设计了具有极低导频碰撞概率的稀疏正交多导频。进一步利用大规模多输入多输出(MIMO)的增益来提高可靠性以及在空域复用大量用户。仿真结果表明,提出的方案可以支持海量Critical MTC终端,同时满足低时延和高可靠的严格要求。

Critical Time and Temper Embrittlement Isotherms

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Mental health status among COVID-19 patients survivors of critical illness in Saudi Arabia:A 6-month follow-up questionnaire study

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODS This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the Hospital Anxiety and Depression Scale(HADS).The primary outcome was the mean HADS score.The secondary outcomes were risk factors of anxiety and/or depression.RESULTS Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADS score for anxiety and depression at 6 months post-ICU discharge was 11.4(SD±8.5).A HADS score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;P<0.05].CONCLUSION Six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADS score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

Critical Solvation Structures Arrested Active Molecules for Reversible Zn Electrochemistry

Aqueous Zn-ion batteries(AZIBs)have attracted increasing attention in next-generation energy storage systems due to their high safety and economic.Unfortunately,the side reactions,dendrites and hydrogen evolution effects at the zinc anode interface in aqueous electrolytes seriously hinder the application of aqueous zinc-ion batteries.Here,we report a critical solvation strategy to achieve reversible zinc electrochemistry by introducing a small polar molecule acetonitrile to form a“catcher”to arrest active molecules(bound water molecules).The stable solvation structure of[Zn(H_(2)O)_(6)]^(2+)is capable of maintaining and completely inhibiting free water molecules.When[Zn(H_(2)O)_(6)]^(2+)is partially desolvated in the Helmholtz outer layer,the separated active molecules will be arrested by the“catcher”formed by the strong hydrogen bond N-H bond,ensuring the stable desolvation of Zn^(2+).The Zn||Zn symmetric battery can stably cycle for 2250 h at 1 mAh cm^(-2),Zn||V_(6)O_(13) full battery achieved a capacity retention rate of 99.2%after 10,000 cycles at 10 A g^(-1).This paper proposes a novel critical solvation strategy that paves the route for the construction of high-performance AZIBs.

Semi-analytical solution for drained expansion analysis of a hollow cylinder of critical state soils

The expansion of a thick-walled hollow cylinder in soil is of non-self-similar nature that the stress/deformation paths are not the same for different soil material points.As a result,this problem cannot be solved by the common self-similar-based similarity techniques.This paper proposes a novel,exact solution for rigorous drained expansion analysis of a hollow cylinder of critical state soils.Considering stress-dependent elastic moduli of soils,new analytical stress and displacement solutions for the nonself-similar problem are developed taking the small strain assumption in the elastic zone.In the plastic zone,the cavity expansion response is formulated into a set of first-order partial differential equations(PDEs)with the combination use of Eulerian and Lagrangian descriptions,and a novel solution algorithm is developed to efficiently solve this complex boundary value problem.The solution is presented in a general form and thus can be useful for a wide range of soils.With the new solution,the non-self-similar nature induced by the finite outer boundary is clearly demonstrated and highlighted,which is found to be greatly different to the behaviour of cavity expansion in infinite soil mass.The present solution may serve as a benchmark for verifying the performance of advanced numerical techniques with critical state soil models and be used to capture the finite boundary effect for pressuremeter tests in small-sized calibration chambers.

Critical dwell time of switched linear systems

In this paper, we consider the relation between the switching dwell time and the stabilization of switched linear control systems. First of all, a concept of critical dwell time is given for switched linear systems without control inputs, and the critical dwell time is taken as an arbitrary given positive constant for a switched linear control systems with controllable switching models. Secondly, when a switched linear system has many stabilizable switching models, the problem of stabilization of the overall system is considered. An on-line feedback control is designed such that the overall system is asymptotically stabilizable under switching laws which depend only on those of uncontrollable subsystems of the switching models. Finally, when a switched system is partially controllable （While some switching models are probably unstabilizable）, an on-line feedback control and a cyclic switching strategy are designed such that the overall system is asymptotically stabilizable if all switching models of this uncontrollable subsystems are asymptotically stable. In addition, algorithms for designing switching laws and controls are presented.

Examination of Silicate Limitation of Primary Production in Jiaozhou Bay, China Ⅱ. Critical Value and Time of Silicate Limitation and Satisfaction of the Phytoplankton Growth

Analysis and comparison of Jiaozhou Bay data collected from May 1991 to February 1994 revealed the spatiotemporal variations of the ambient Si(OH) 4∶NO 3 (Si∶N) concentration ratios and the seasonal variations of (Si∶N) ratios in Jiaozhou Bay and showed that the Si∶N ratios were < 1 throughout Jiaozhou Bay in spring, autumn, and winter. These results provide further evidence that silicate limits the growth of phytoplankton (i.e. diatoms) in spring, autumn and winter. Moreover, comparison of the spatiotemporal variations of the Si∶N ratio and primary production in Jiaozhou Bay suggested their close relationship. The spatiotemporal pattern of dissolved silicate matched well that of primary production in Jiaozhou Bay. Along with the environmental change of Jiaozhou Bay in the last thirty years, the N and P concentrations tended to rise, whereas Si concentration showed cyclic seasonal variations. With the variation of nutrient Si limiting the primary production in mind, the authors found that the range of values of primary production is divided into three parts: the basic value of Si limited primary production, the extent of Si limited primary production and the critical value of Si limited primary production, which can be calculated for Jiaozhou Bay by Equations (1), (2) and (3), showing that the time of the critical value of Si limitation of phytoplankton growth in Jiaozhou Bay is around November 3 to November 13 in autumn; and that the time of the critical value of Si satisfaction of phytoplankton growth in Jiaozhou Bay is around May 22 to June 7 in spring. Moreover, the calculated critical value of Si satisfactory for phytoplankton growth is 2.15-0.76 μmol/L and the critical value of Si limitation of phytoplankton growth is 1.42-0.36 μmol/L; so that the time period of Si limitation of phytoplankton growth is around November 13 to May 22 in the next year; the time period of Si satisfactory for phytoplankton growth is around June 7 to November 3. This result also explains why critical values of nutrient silicon affect phytoplankton growth in spring and autumn are different in different waters of Jiaozhou Bay and also indicates how the silicate concentration affects the phytoplankton assemblage structure. The dilution of silicate concentration by seawater exchange affects the growth of phytoplankton so that the primary production of phytoplankton declines outside Jiaozhou Bay earlier than inside Jiaozhou Bay by one and half months. This study showed that Jiaozhou Bay phytoplankton badly need silicon and respond very sensitively and rapidly to the variation of silicon.

Theoretical and experimental studies on critical time delay of multi-DOF real-time hybrid simulation

This paper aims to investigate the critical stability of a multi-degree-of-freedom(multi-DOF)real-time hybrid simulation(RTHS).First,the critical time-delay analysis models are developed using the continuous-and discrete-time root locus(RL)techniques,respectively.A bilinear transform is introduced into the first-order Padéapproximation while conducting the discrete RL analysis.Based on this technique,the time delay can be explicitly used as the gain factor and thus the instability mechanism of the multi-DOF RTHS system can be analyzed.Subsequently,the critical time delays calculated by the continuous-and discrete-time RL techniques,respectively,are compared for a 2-DOF RTHS system.It is shown that assuming the RTHS system to be a continuous-time system will result in overestimating the critical time delay.Finally,theoretically calculated critical delays are demonstrated and validated by numerical simulation and a set of RTHS experiments.Parametric analysis provides a glimpse of the effects of time step,frequency and damping ratio in a performing partitioning scheme.The constructed analysis model proves to be useful for evaluating the critical time delay to predict stability and performance,therefore facilitating successful RTHS.

A Critical Review of Viewpoints on the Time of the Origin of Hongqu(Red Yeast Rice)

Through a summary of the results of past research on the time of the origin of hongqu(红曲,red yeast rice),a critical review is made of multiple pieces of published evidence supporting the various viewpoints that hongqu originated from the Han,Wei,Jin,Tang,or Song dynasties.Based on a newly discovered textual comment by Kong Guangtao孔广陶(1832–1890)that rectified the mistake of mis-quoting“red wheat powder in Guazhou”(Guazhou hongzhi瓜州红)as“red yeast rice in Guazhou”(Guazhou hongqu瓜州红麯)in Entry into Learning(Chuxue ji初学记),a conclusion can be drawn that the evidence for a Han dynasty origin that has dominated for nearly forty years is not well-grounded,and proposes that Chinese hongqu originated in the Tang dynasty(618–907).

Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo microcomputed tomographic and histologic e

The aim of the present real time in vivo micro-computed tomography （pCT） and histologic experiment was to assess the efficacy of guided bone regeneration （GBR） around standardized calvarial critical size defects （CSD） using bone marrow-derived mesenchymal stem cells （BMSCs）, and collagen membrane （CM） with and without tricalcium phosphate （TCP） graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD （diameter 4.6 mm） were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone （NFB） and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo pCT. At the lOth week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups I and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical ＂lock＂ between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adiunct BMSC therapy.

Effect of Holding Time on the Microstructure and Mechanical Properties of Dual-Phase Steel during Intercritical Annealing

Continuous annealing simulation tests were conducted by using a continuous annealing thermomechanical simulator. Holding times of 5, 60, 180, and 480 seconds for an intercritical annealing temperature of 820℃ were adopted to investigate the evolution of the mierostructure and mechanical properties of ferrite-bainite dual-phase steel. The ferrite-bainite dual-phase steel was characterized by high strength and low yield ratio due to the presence of the constituents （polygonal ferrite, bainite, martensite and retained austenite） of the steel microstructure. Specimen 3 exhibits the highest value of A50 （7.67%） and a product of Rm × A50 （10453MPa%） after a 180s holding. This is likely attributed to the presence of a C-enriched retained anstenite in the microstructure. And the effect of martensite islands and carbide precipitate is thought to be able to contribute in strengthening the present steel. It is expected that equilibrium of anstenite fraction would be reached for reasonable intercritical holding period, regardless of the heating temperature. The results suggest that long increasing holding times may not be needed because the major phase of the microstructure does not change very significantly. It is favorable for industrial production of DP steels to shorten holding times. Key words： ferrite-bainite dual-phase steel; holding time; martensite islands; mechanical properties

Enhancing Critical Path Problem in Neutrosophic Environment Using Python

In the real world,one of the most common problems in project management is the unpredictability of resources and timelines.An efficient way to resolve uncertainty problems and overcome such obstacles is through an extended fuzzy approach,often known as neutrosophic logic.Our rigorous proposed model has led to the creation of an advanced technique for computing the triangular single-valued neutrosophic number.This innovative approach evaluates the inherent uncertainty in project durations of the planning phase,which enhances the potential significance of the decision-making process in the project.Our proposed method,for the first time in the neutrosophic set literature,not only solves existing problems but also introduces a new set of problems not yet explored in previous research.A comparative study using Python programming was conducted to examine the effectiveness of responsive and adaptive planning,as well as their differences from other existing models such as the classical critical path problem and the fuzzy critical path problem.The study highlights the use of neutrosophic logic in handling complex projects by illustrating an innovative dynamic programming framework that is robust and flexible,according to the derived results,and sets the stage for future discussions on its scalability and application across different industries.

Predicted Critical State Based on Invariance of the Lyapunov Exponent in Dual Spaces

Critical states in disordered systems,fascinating and subtle eigenstates,have attracted a lot of research interests.However,the nature of critical states is difficult to describe quantitatively,and in general,it cannot predict a system that hosts the critical state.We propose an explicit criterion whereby the Lyapunov exponent of the critical state should be 0 simultaneously in dual spaces,namely the Lyapunov exponent remains invariant under the Fourier transform.With this criterion,we can exactly predict a one-dimensional quasiperiodic model which is not of self-duality,but hosts a large number of critical states.Then,we perform numerical verification of the theoretical prediction and display the self-similarity of the critical state.Due to computational complexity,calculations are not performed for higher dimensional models.However,since the description of extended and localized states by the Lyapunov exponent is universal and dimensionless,utilizing the Lyapunov exponent of dual spaces to describe critical states should also be universal.Finally,we conjecture that some kind of connection exists between the invariance of the Lyapunov exponent and conformal invariance,which can promote the research of critical phenomena.