Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

The effectiveness of physical activity interventions on blood pressure in children and adolescents:A systematic review and network meta-analysis

Background:High blood pressure(BP)is a major contributor to mortality and cardiovascular diseases.Despite the known benefits of exercise for reducing BP,it is crucial to identify the most effective physical activity(PA)intervention.This systematic review and network meta-analysis(NMA)aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.Methods:A search of PubMed,SPORTDiscus,PsycINFO,Web of Science,CINAHL,Cochrane,and Eric databases was conducted up to December 2022 for this systematic review and NMA.Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6-12 years old were included in this study.Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines.Three independent investigators performed the literature screening,data extraction,and risk of bias assessment.We used Bayesian arm-based NMA to synthesize the data.The primary outcomes were systolic BP and diastolic BP.We calculated the mean differences(MDs)in systolic BP and diastolic BP before and after treatment.Mean treatment differences were estimated using NMA and random-effect models.Results:We synthesized 27 studies involving 15,220 children and adolescents.PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP(MD=-8.64,95%credible interval(95%CI):-11.44 to-5.84;MD=-6.75,95%CI:-10.44 to-3.11),followed by interventions with multiple components(MD=-1.39,95%CI:-1.94 to-0.84;MD=-2.54,95%CI:-4.89 to-0.29).Conclusion:Our findings suggest that PA interventions incorporating nutrition and behavior change,followed by interventions with multiple components,are most effective for reducing both systolic BP and diastolic BP in children and adolescents.

Editorial Commentary:Copper Homeostasis in Neurodegenerative Diseases

Copper,as an essential trace nutrient,plays a crucial role in biological processes such as mitochondrial respiration,antioxidant stress response,and the synthesis of biomolecules.Typically,cellular copper concentrations are maintained at very low levels,a pattern also observed in cancer cells to prevent adverse consequences of copper overload,such as cuproptosis.This involves copper dependency,accumulation of lipidated proteins,and a reduction in Fe-S cluster proteins[1].Various neurodegenerative diseases are associated with imbalances in copper homeostasis.

Association of Thyroid Nodules with Various Elements in Urine and Blood Serum: A Case-Control Study

Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.

Detection of Al, Mg, Ca, and Zn in copper slag by LIBS combined with calibration curve and PLSR methods

The precise measurement of Al, Mg, Ca, and Zn composition in copper slag is crucial for effective process control of copper pyrometallurgy. In this study, a remote laser-induced breakdown spectroscopy(LIBS) system was utilized for the spectral analysis of copper slag samples at a distance of 2.5 m. The composition of copper slag was then analyzed using both the calibration curve(CC) method and the partial least squares regression(PLSR) analysis method based on the characteristic spectral intensity ratio. The performance of the two analysis methods was gauged through the determination coefficient(R^(2)), average relative error(ARE), root mean square error of calibration(RMSEC), and root mean square error of prediction(RMSEP). The results demonstrate that the PLSR method significantly improved both R^(2) for the calibration and test sets while reducing ARE, RMSEC, and RMSEP by 50% compared to the CC method. The results suggest that the combination of LIBS and PLSR is a viable approach for effectively detecting the elemental concentration in copper slag and holds potential for online detection of the elemental composition of high-temperature molten copper slag.

Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

Heterogeneous patterning of blood-brain barrier and adaptive myelination as renewing key in gray and white matter

Background:Development and homeostasis of the brain are enabled through the precise control of the cell microenvironment by the blood-brain barrier(BBB),which interfaces between the brain parenchyma and the lumen of blood microvessels,and by the blood-cerebrospinal fluid barrier,which separates the cerebrospinal fluid from the blood vessels of the choroid plexus(Villabona-Rueda et al.,2019).Here,the focus will be on the BBB,the impairment of which is considered the earliest common denominator in neurovascular diseases.

Screening, Treatment and Control of High Blood Pressure on Five Sites in Mali

Introduction: High blood pressure is defined as blood pressure greater than or equal to 140 mm Hg for systolic and or 90 mm Hg for diastolic. It constitutes a major public health problem, the leading chronic disease in the world. The objective was to determine the prevalence, treatment rate and control of hypertension. Methods: This was a cross-sectional and descriptive study which took place over a period of 6 months in a hospital environment and in the general population. Results: Of the 1000 participants, 637 had hypertension, giving a prevalence of 63.70% with a female predominance. Thirty-three percent (33%) were unaware of their high blood pressure. The age group 60 and more was the most represented (44%). A proportion of 33 and 23.20 were overweight and obese participants, respectively. Male subjects were more overweight than female, unlike obesity which was more common among female subjects. Sixty-two percent (62%) of hypertensives were treated, of whom 44% were non-compliant. The excessively high cost and consumption of medications as needed were the main factors in therapeutic non-compliance. Twenty-two percent (22%) of all hypertensive patients and 35% of treated hypertensive patients were controlled. Women were more treated but less observant and less controlled than men. Therapeutic coverage and combination therapy rates were lower in rural areas. Hypertensives who had a high level of education were better treated and controlled than those who had no level. Conclusion: High blood pressure remains a real public health problem in Mali. It is more common in people aged 60 and over and in females. One in three hypertensives were unaware of their hypertension. The majority received antihypertensive treatments, but only a minority of them had their hypertension controlled.

Using Optical Tweezers to Study the Friction of the Red Blood Cells

In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).

Purification of copper foils driven by single crystallization

High-purity copper(Cu) with excellent thermal and electrical conductivity, is crucial in modern technological applications, including heat exchangers, integrated circuits, and superconducting magnets. The current purification process is mainly based on the zone/electrolytic refining or anion exchange, however, which excessively relies on specific integrated equipment with ultra-high vacuum or chemical solution environment, and is also bothered by external contaminants and energy consumption. Here we report a simple approach to purify the Cu foils from 99.9%(3N) to 99.99%(4N) by a temperature-gradient thermal annealing technique, accompanied by the kinetic evolution of single crystallization of Cu.The success of purification mainly relies on(i) the segregation of elements with low effective distribution coefficient driven by grain-boundary movements and(ii) the high-temperature evaporation of elements with high saturated vapor pressure.The purified Cu foils display higher flexibility(elongation of 70%) and electrical conductivity(104% IACS) than that of the original commercial rolled Cu foils(elongation of 10%, electrical conductivity of ~ 100% IACS). Our results provide an effective strategy to optimize the as-produced metal medium, and therefore will facilitate the potential applications of Cu foils in precision electronic products and high-frequency printed circuit boards.

OsMYB84,a transcriptional regulator of OsCOPT2 and OsHMA5,modulates copper uptake and transport and yield production in rice

Transcription factors regulating crop uptake and translocation of the micronutrient Cu have not been identified.We isolated a novel R2R3-MYB transcription factor,OsMYB84,and showed that it was a positive regulator involved in uptake and transport of Cu via activation of OsCOPT2 and OsHMA expression.OsMYB84 was highly expressed in roots and anthers and induced by Cu.Overexpression of OsMYB84 promoted uptake and root-to-shoot translocation of Cu in rice,facilitated Cu distribution into grain and increased grain yield.In contrast,mutation of OsMYB84 reduced Cu concentration in xylem sap.OsMYB84 bound to the promoter region of OsCOPT2 and OsHMA5 and upregulated their expression.OsCOPT2 mutants showed reduced uptake of Cu and OsHMA5 overexpression lines showed increased root-to-shoot translocation of Cu.

Role of copper chelating agents: between old applications and new perspectives in neuroscience

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

Economic Stress, Precariousness and Risk of High Blood Pressure: A Descriptive Survey of Life Models within Households of the Central Region of Cameroon

Context/Objective: High blood pressure (HBP) currently represents the most widespread chronic non-communicable disease in Cameroon. The increase in its prevalence in the country is the result of multiple factors including economic stress imposed by precariousness, poor living conditions, sources of anxiety, anguish, depression and other behavioral disorders. Economic stress is a globalizing concept that integrates into a purely hermeneutic approach, a particular functioning of the nervous system of an individual who faces employment problems and precarious remuneration conditions. The non-satisfaction by an individual of his basic needs due to insufficient financial means can cause him to become irritable, aggressive, and socially and symbolically isolated, thereby increasing the desire to resort to morbid life models such as excessive consumption of narcotics and other psychoactive substances often associated with high blood pressure. The fight against the emergence of BPH is a complex, multifaceted and multifactorial reality that requires taking into account economic stress. The main objective of this survey is to describe the situation of economic stress within the Cameroonian population, which imposes precariousness and life models at risk of high blood pressure. Specifically, we determined the level of household income and the sources of income. Methods: A cross-sectional survey with a descriptive aim among five hundred households in the Central Region of Cameroon was conducted. A probabilistic technique called simple randomness was used. The number of households to be surveyed was determined indirectly using the Cochrane formula. Data collection in face-to-face mode using a physical questionnaire took place from July 1 to August 31, 2023, after obtaining ethical clearance from the Regional Health Research Ethics Committee, Human from the Center and an administrative authorization for data collection. Regarding their processing, the data was grouped during processing in Excel sheets. Normality and reliability tests of the collected data were carried out. For this, the Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value. Descriptive analysis was possible using R software version 3.2, SPSS version 25.0, XLSTAT 2016, PAST and EXCEL programs from Microsoft Office 2013. Results: The main results highlight economic stress, with 45.60% of households surveyed earning less than US$154 per month;55% of household heads were women in single-parent families;14% of household heads were unemployed, 22% worked in the private sector and 19% were self-employed. This general economic situation leads to precarious living conditions, thereby increasing the risk of high blood pressure among the Cameroonian population.

Blood Pressure Estimation with Phonocardiogram on CNN-Based Approach

Monitoring blood pressure is a critical aspect of safeguarding an individual’s health,as early detection of abnormal blood pressure levels facilitates timely medical intervention,ultimately leading to a reduction in mortality rates associated with cardiovascular diseases.Consequently,the development of a robust and continuous blood pressure monitoring system holds paramount significance.In the context of this research paper,we introduce an innovative deep learning regression model that harnesses phonocardiogram(PCG)data to achieve precise blood pressure estimation.Our novel approach incorporates a convolutional neural network(CNN)-based regression model,which not only enhances its adaptability to spatial variations but also empowers it to capture intricate patterns within the PCG signals.These advancements contribute significantly to the overall accuracy of blood pressure estimation.To substantiate the effectiveness of our proposed method,we meticulously gathered PCG signal data from 78 volunteers,adhering to the ethical guidelines of Suranaree University of Technology(Human Research Ethics number EC-65-78).Subsequently,we rigorously preprocessed the dataset to ensure its integrity.We further employed a K-fold cross-validation procedure for data division and alignment,combining the resulting datasets with a CNNfor blood pressure estimation.The experimental results are highly promising,yielding aMeanAbsolute Error(MAE)and standard deviation(STD)of approximately 10.69±7.23 mmHg for systolic pressure and 6.89±5.22 mmHg for diastolic pressure.Our study underscores the potential for precise blood pressure estimation,particularly using PCG signals,paving the way for a practical,non-invasive method with broad applicability in the healthcare domain.Early detection of abnormal blood pressure levels can facilitate timely medical interventions,ultimately reducing cardiovascular disease-related mortality rates.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

Copper slag assisted coke reduction of phosphogypsum for sulphur dioxide preparation

The reduction of phosphogypsum(PG)to lime slag and SO_(2)using coke can effectively alleviate the environmental problems caused by PG.However,the PG decomposition temperature remains high and the product yield remains poor.By adding additives,the decomposition temperature can be further reduced and PG decomposition rate and product yield can be improved.However,the use of current additives such as Fe_(2)O_(3)and SiO_(2)brings the problem of increasing economic cost.Therefore,it is proposed to use solid waste copper slag(CS)as a new additive to reduce PG to prepare SO2,which can reduce the cost and meet the environmental benefits at the same time.The effects of proportion,temperature and thermostatic time on PG decomposition are investigated by experimental and kinetic analysis combined with FactSage thermodynamic calculations to optimize the roasting conditions.Finally,the reaction mechanism is proposed.It is found that adding CS to the coke and PG system can increase the rate of PG decomposition and SO_(2)yield while lowering the PG decomposition temperature.For example,when the CS/PG mass ratio increases from 0 to 1,PG decomposition rate increases from 83.38%to 99.35%,SO_(2)yield increases from 78.62%to 96.81%,and PG decomposition temperature decreases from 992.4℃to 949.6℃.The optimal reaction parameters are CS/PG mass ratio of 1,Coke/PG mass ratio of 0.06 at 1100℃for 20 min with 99.35%PG decomposition rate and 96.81%SO_(2) yield.The process proceeds according to the following reactions:2CaSO_(4)+ 0.7C + 0.8Fe_(2)SiO_(4)→0.8Ca_(2)SiO_(4)+ 0.2Ca_(2)Fe_(2)O_(5)+ 0.4Fe_(3)O_(4)+2SO_(2)+ 0.7CO_(2)Finally,a process for decomposing PG with coke and CS is proposed.

Hemoglobin loss method calculates blood loss during pancreaticoduodenectomy and predicts bleeding-related risk factors

BACKGROUND The common clinical method to evaluate blood loss during pancreaticoduoden-ectomy(PD)is visual inspection,but most scholars believe that this method is extremely subjective and inaccurate.Currently,there is no accurate,objective me-thod to evaluate the amount of blood loss in PD patients.We retrospectively analyzed the clinical data of 341 patients who underwent PD in Shandong Provincial Hospital from March 2017 to February 2019.According to different surgical methods,they were divided into an open PD(OPD)group and a laparoscopic PD(LPD)group.The differences and correlations between the in-traoperative estimation of blood loss(IEBL)obtained by visual inspection and the intraoperative calculation of blood loss(ICBL)obtained using the Hb loss method were analyzed.ICBL,IEBL and perioperative calculation of blood loss(PCBL)were compared between the two groups,and single-factor regression analysis was performed.RESULTS There was no statistically significant difference in the preoperative general patient information between the two groups(P>0.05).PD had an ICBL of 743.2(393.0,1173.1)mL and an IEBL of 100.0(50.0,300.0)mL(P<0.001).There was also a certain correlation between the two(r=0.312,P<0.001).Single-factor analysis of ICBL showed that a history of diabetes[95%confidence interval(CI):53.82-549.62;P=0.017]was an independent risk factor for ICBL.In addition,the single-factor analysis of PCBL showed that body mass index(BMI)(95%CI:0.62-76.75;P=0.046)and preoperative total bilirubin>200μmol/L(95%CI:7.09-644.26;P=0.045)were independent risk factors for PCBL.The ICBLs of the LPD group and OPD group were 767.7(435.4,1249.0)mL and 663.8(347.7,1138.2)mL,respectively(P>0.05).The IEBL of the LPD group 200.0(50.0,200.0)mL was slightly greater than that of the OPD group 100.0(50.0,300.0)mL(P>0.05).PCBL was greater in the LPD group than the OPD group[1061.6(612.3,1632.3)mL vs 806.1(375.9,1347.6)mL](P<0.05).CONCLUSION The ICBL in patients who underwent PD was greater than the IEBL,but there is a certain correlation between the two.The Hb loss method can be used to evaluate intraoperative blood loss.A history of diabetes,preoperative bilirubin>200μmol/L and high BMI increase the patient's risk of bleeding.

Excess dietary Lys reduces feed intake, stimulates jejunal CCK secretion and alters essential and non‑essential blood AA profile in pigs

Background Commercial diets are frequently formulated to meet or exceed nutrient levels including those of lim-iting essential amino acids(AA)covering potential individual variations within the herd.However,the provision of dietary excess of AA,such as Lys,may lead to reduced appetite and growth in pigs.The mechanisms modulat-ing these responses have not been extensively investigated.This study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning pigs.Methods Twenty-four pigs aged 21 d and weighing 6.81±0.12kg(mean±SEM)were individually housed and offered 1 of 4 dietary treatments for 3weeks:a diet containing a standardized ileal digestible Lys reaching 100%(T0),120%(T1),150%(T2)or 200%(T3)of the NRC(2012)requirements.At the end of the experiment,blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA analysis.In addition,primary intestinal cultures from T0 pigs were used,following their humane killing,to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo conditions.Results Feed intake was linearly reduced(P<0.001)and the weight gain to feed ratio reduced(P<0.10)with increased dietary levels of Lys during the third-and first-week post weaning,respectively.Cholecystokinin con-centration(P<0.05)and the metabotropic glutamate receptor 1 and the solute carrier family 7 member 2(P<0.10)gene expression was enhanced in proximal jejunum tissues incubated with Lys at 20mmol/L when compared to the control(Lys 0mmol/L).Plasma Lys and Glu(P<0.05)concentration increased in the T3 compared to T0 pigs.In contrast,plasma levels of His,Val,Thr,Leu(P<0.05)and Gln(P<0.10)were lower in T3 than T0 pigs.Conclusion The present results confirm that excess dietary Lys inhibits hunger in pigs.Moreover,the results provide evidence of pre-and post-absorptive mechanisms modulating these responses.Lys dietary excesses should be nar-rowed,when possible,to avoid negative effects of the AA on appetite in pigs.