NECAB family of neuronal calcium-binding proteins in health and disease

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

Preparation and applications of calcium ferrite as a functional material:A review

Calcium ferrite(CF)is recognized as a potential green and efficient functional material because of its advantages of magnetism,electrochemistry,catalysis,and biocompatibility in the fields of materials chemistry,environmental engineering,and biomedicine.There-fore,the obtained research results need to be systematically summarized,and new perspectives on CF and its composite materials need to be analyzed.Based on the presented studies of CF and its composite materials,the types and structures of the crystal are summarized.In addition,the current application technologies and theoretical mechanisms with various properties in different fields are elucidated.Moreover,the various preparation methods of CF and its composite materials are elaborated in detail.Most importantly,the advantages and disadvantages of the synthesis methods of CF and its composite materials are discussed,and the existing problems and emerging challenges in practical production are identified.Furthermore,the key future research directions of CF and its composite materials have been prospected from the potential application technologies to provide references for its synthesis and efficient utilization.

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

Role of Inhibition of Osteogenesis Function by Sema4D/Plexin-B1 Signaling Pathway in Skeletal Fluorosis In Vitro

Summary： Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B 1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-β1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-β1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin （OPG） secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.

Association of Dietary Carotenoids Intake with Skeletal Fluorosis in the Coal-burning Fluorosis Area of Guizhou Province

Objective To explore whether the intake of dietary carotenoids could protect against skeletal fluorosis in Guizhou province in which coal-burning fluorosis is endemic. Methods A case-control study of 196 patients with skeletal fluorosis and 196 age and gender-matched controls was conducted in Zhijin, Guizhou Province. Face-to-face interviews were conducted to assess habitual dietary intake using a 75-item food frequency questionnaire and various covariates with structured questionnaires. Urinary fluoride was measured using an ion-selective electrode method. The genotype of superoxide dismutase 2（SOD2） rs11968525 was detected by Taq Man method. Results We observed significant dose-dependent inverse associations of skeletal fluorosis with intake of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids（P-trend = 0.002 to 0.018）, whereas α-carotene and β-cryptoxanthin intakes were not found to be related to skeletal fluorosis, after adjustment for potential confounders. The adjusted ORs and 95% CI of skeletal fluorosis for the highest versus lowest quartile were 0.30（0.10, 0.86） for β-carotene, 0.23（0.08, 0.66） for lycopene, 0.26（0.10, 0.75） for lutein/zeaxanthin and 0.34（0.14, 0.74） for total carotenoids（all P-trend ＆lt; 0.05）. Stratified analyses showed that the protective effects of lutein/zeaxanthin and total carotenoids on skeletal fluorosis were more evident for individuals with the AG＋AA genotypes of SOD2（rs11968525）. Conclusion Increased intakes of β-carotene, lutein/zeaxanthin, lycopene, and total carotenoids are independently associated with a lower risk of coal-burning skeletal fluorosis. SOD2（rs11968525） polymorphisms might modify the inverse associations between dietary carotenoids and skeletal fluorosis.

Relationships between daily total fluoride intake and dental fluorosis and dental caries

Objective： To explore the relationships between the daily total intake of fluoride, dental fluorosis and dental caries. Methods： An epidemiological method was used to investigate the daily total intake of fluoride, dental fluorosis, and dental caries among 236 and 290 children aged 8-13 years in a severe endemic area and in a non-fluorosis control area, respectively. The children were divided into eight subgroups according to each child＇ s estimated daily total intake of fluoride. The prevalence of dental fluorosis and dental caries in each group was calculated. Results： As expected, elevated levels of fluoride intake were significantly associated with a higher prevalence of dental fluorosis and an increasing amount of more severe defect dental fluorosis. When the daily total F intake was 2.78 mg/child/day, the prevalence of dental fluorosis was nearly 100%, with the prevalence of defect dental fluorosis increasing with increasing fluoride intake. There was also a significant negative（inverse） dose-response relationship between the daily total intake of fluoride and the overall prevalence of dental caries, the prevalence of which decreased when the daily total intake of fluoride increased up to 3.32 mg/child/day. However, at higher levels of daily total intake of fluoride the prevalence of dental caries increased, giving rise to a U-shaped dose-response relationship curve. Conclusion： It is important to monitor total fluoride exposure and protect children from excessive fluoride intake, especially during the years of tooth development.

Investigation and Analysis on Current Situation of Coal-Burning Fluorosis Prevalence

Objective: The purpose of the paper is to provide the result from investigation on the current situation of coal-burning fluorosis prevalence in Chongqing City and make an assessment on the prevention and curing measures. Method: The Dean’s Method is applied to investigate on the fluorotic teeth of locally-born children aged between 8 to 12;investigate how modified cooking stoves are utilized by households and how food maize and hot pepper are being dried;and test the urinary fluorine content and pepper fluorine content. Result: The investigations show that, in the 661 villages with illness history from the 100 townships of 13 districts in Chongqing City, 11.28% (7464/ 66,162) of the children aged between 8 and 12 suffer from dental fluorosis;the stoves modified rate, qualified rate of modified stoves, and correct utilization rate of qualified modified stoves are respectively 100%, 98.82%, and 99.45%;and food maize and hot pepper’s drying rates are respectively 99.88% and 99.75%. Conclusion: The result shows that the coal-burning type fluorosis prevalence in the endemic area of Chongqing City has decreased dramatically, the preventive measure is effectively implemented, and a long-term preventive mechanism has preliminarily been established.

Relationship between the Contents of MDA, the Activity of SOD in Serum of the Milk Goat with Fluorosis and the Erythrocytic Membrane Liquidity

To research the relation among the erythrocytic membrane.liquidity and the contents of MDA, the activity of SOD in serum of the milk goat with fluorosis. An animal model with fluorosis was constructed, and the fluorescent probe technique of DPH was used to measue the erythrocytic membrane liquidity. At the same time, the contents of MDA and the activity of SOD in serum were measured. The results showed that the erythrocytic membrane liquidity in the control group and flurosis group were 5.6742 ± 0.4417 and 3.7248 ± 0.4521 （P 〈0.01） respectively, the contents of MDA in serum were 2.0408 ± 0.198 and 4.494± 0.438 （P 〈0.01） respectively, the activities of SOD were 175.638 ± 22.201 and 113.714 ± 34.258 （P 〈0.01） respectively. The correlation analysis indicated that the relation between the activity of SOD and the liquidity of erythrocytic membrane was positive correlation （ r= 0.7321, P 〈0.05）, whereas the relation between the contents of MDA and the liquidity of erythrocytic membrane was negative correlation （r = -0.6438, P 〈0.01）. The erythrocytic membrane liquidity decreased in milk goat with fluorosis, which played a role in the occurrence and development of the fluorosis. There was correlation among the erythrocytic membrane liquidity and the contents of MDA, the activity of SOD.

Prevalence of Brick Tea-type Fluorosis in Children Aged 8–12 Years in Qinghai Province,China

Fluorosis is a serious health problem,and an endemic disease in certain areas in China,India,and some countries in Africa[1].There are three types of fluorosis which includes drinking-water type fluorosis,coal-burning pollution type fluorosis,and brick tea-type fluorosis.Coal-burning pollution type fluorosis and brick tea-type fluorosis are found only in China's Mainland mainland.

Influence of high-fluorine environmental background on crops and human health in hot spring-type fluorosis-diseased areas

Drinking water-type fluorosis is the most harmful endemic disease in China with the largest number of sufferers. Although the implementation of the policy to alter water sources to lower fluoride level has effectively controlled the spread of this kind of endemic disease,its prevalence could not thoroughly be stopped because the high-fluoride environmental background in these endemically diseased areas could still do harm to human health through food chain. Therefore,it is necessary to conduct a more deep-going study on the drinking water-type fluoro-sis. To investigate the effect of high fluorine environmental background on crops and human health in the hot spring-type fluorosis-diseased areas,local water,paddy soil,rice,whole vegetables and soils around their roots were sampled for analysis. The results were compared with those of the control groups in fluorosis-free areas which are similar to the fluorosis-diseased areas both in natural background and in social background. It is indicated that rice and vegetables can accumulate water-soluble fluorine either in soils or in irrigating water,and different crops have different abilities of fixing fluorine. The contents of fluorine in different parts of vegetables in the fluorosis-diseased and fluorosis-free areas were statistically categorized. The results showed that the fluorine contents of roots,tubers,leaves and flowers of vegetables in the fluorosis-diseased areas are 3.56,1.17,3.07 and 3.23 mg/kg,respectively. However,comparisons showed that in the fluorosis-free areas,the fluorine contents are 2.17,0.70,1.91 and 2.52 mg/kg,respectively. Moreover,different parts of a crop also show significantly different fluorine fixation abilities. It is demonstrated that the fluorine contents of the strongly metabolic parts are relatively high. For example,the fluo-rine contents of roots,leaves and flowers of vegetables are much higher than those of stems. The fluorine fixation ability of seeds is very weak. In order to reduce the risk of human body’s exposure to fluoride,the impact of hot spring water on the capability of crops to fix fluorine should be reduced as much as possible. It is of great importance to prevent crops from being irrigated with hot spring water and it is advisable to grow crops with relatively low ca-pabilities to enrich fluorine,such as those with seeds or tubers as the main edible parts in the areas which are se-verely affected by hot spring water.

GEOGRAPHICAL ENVIRONMENTAL CHARACTERISTICS OF ENDEMIC FLUOROSIS IN CHINA

Endemic fluorosis is given rise to by human intake of excess fluorine from environment by way of food chain. In China it is one of the extensively prevalent endemic diseases and its distribution shows clearly regional characteristics. In macroscopic sight, three large fluorosis zones may be divided: (1) The arid and semi-arid plains in the north of China. These regions have a dry climate, making fluorine accumulation in the Quaternary deposits. Thus, the drinking water with high content of fluorine is the main cause of the disease formation. (2) The Yunnan-Guizhou Plateau. In the region, rocks and soils rich in fluorine bring about fluorine excess in crop food. This plays an important role in the disease formation. (3) Southeast hills. The hot spring with high content of fluorine leads to fluorosis.The fluorine absorbed by people from the environment is firstly from the drinking water and secondly from the crop food originating from soil. The fluorine in the air can be accumulated in crop leaves to

Pathological evaluation of pancreatic exocrine glands in experimental fluorosis

Objective:To monitor the pathological alterations in pancreas of rat during experimental fluorosis. Methods:Sixty Sprague Dawley albino rats of both sexes were divided into 12 experimental groups and one control group.The rats of control group were administered subcutaneously double distilled water 1 mL/kg bw daily.The experimental groups were injected with 30,45,and 75 mg NaF/kg bw/day.The experimental period was divided into 4 phases at interval of 15,22,30,and 36 days.Animals were sacrificed from each group at the end of 16,23,31,and 37 days.Results: The following changes were observed in this study:(1) Pathological examination of pancreas after 15 days of fluoride treatment revealed:hypertrophy of acini,leucocytes infilteration and pycnouc nuclei due to necrosis of acini in group 1;uremic alterations,invulsion and infoldings of reticular layer of islets of Langerhans in group 2;and a decrease in number of acini and interlobular connective tissues resulted in an increase in intercellular spaces in pancreas of rats in group 3.(2)Hyalinization and hypertrophy in the lobules of acini and hyperplasia and hypertrophy in intercalated duct with mucinous secretion in pancreas of rat of group 4;squamous metaplasia of pancreatic duct,adenoma of pancreas,hemorrhagic necrosis in group 5;and hyperplasia of acini and reduction in number of pancreatic islets in group 6.(3) Disorganization and atrophy of pancreatic lobules and presence of vacuoles in a group of six were visible in pancreas of rats in group 7;acute pancreatic and lamellated inflammatory cells in test rats of group 8;and islet adenoma and decrease in number of islets cells,and exudation in acini were noticed in experimental rats of group 9.(4) In the last phase of experimentation,atrophic alterations in pancreatic acini,invulsions,and necrosis was prominent in group 10,deep inflammation and proliferation of connective tissue of pancreas in experimental group 11,and periodical fibrosis, hyperplasia of acini,degenerative changes in pancreas of rats in group 12.Conclusion:The histopathological examination of pancreas of fluoridated rats exhibited structural alterations in the exocrine glands.The acini revealed hypertrophy,pyknotic nucleus,necrosis and uremic alterations.Acini became lobulated and reveal increased pigmentation.

Changes of Serotonin content and Turnover Rate in Hypothalamus of Female Rat during Fluorosis

The animal models of subacute and chronic fluorosis were devel-oped with injection of large doses of NaF (IP)and drinking water containing100 ppm F^- in female rats respectively. Serotonin content and turnover rate inhypothalamus of rat were determined with spectrofluorometry combined degra-dation blockade. 5-HT turnover rate in hypothalamus decreased during bothsubacute and chronic fluorosis. 5-HT content in hypothalamus increased duringsubacute fluorosis, but decreased during chronic fluorosis. These results suggestthat the influences on 5-HT metabolism of two kinds of fluorosis are not com-pletely identical. The decrease of 5-HT turnover rate in hypothalamus may be one of thepossible mechanisms of deficiency of pituitary prolactin and milk secretion dur-ing fluorosis.

Complete oral rehabilitation in a case with severe dental fluorosis

The authors have presented a technique of full occlusal rehabilitation in a case of severe dental fluorosis. In this technique, maxillary and mandibular anterior teeth were simultaneously prepared and restored first. This was followed by simultaneous preparation of maxillary and mandibular posterior teeth that were restored in canine guided occlusion. The technique and sequence followed here is unique and is not available in dental literature. This technique reduces number of appointments while fulfilling all objectives. Periodontal followup over 3 years was satisfactory. A restorative treatment protocol has been devised for fluorosis which will act as a guide for the dental practitioners.

Groundwater Quality and Its Impact on Health: A Preliminary Evaluation of Dental Fluorosis in Julimes, Chihuahua, Mexico

Medical Geology can be defined as the branch of geology dealing with the relationship between natural geological aspects and health in organisms (humans and animals), trying to determine the influence of ordinary environmental factors on the geographical distribution of health issues. The main goals of this research were: 1) to evaluate the severity of dental fluorosis (DF) and fluoride concentration in groundwater, used for human consumption, as an indicator of overexposure to fluorides, 2) to estimate the Community Fluorosis Index (CFI) in the Julimes municipality in Chihuahua, Mexico. Nine water samples were collected in four locations in the Julimes area: Hacienda Humboldt, La Regina, Colonia San Jose, and Julimes. Samples were collected and stored in accordance with the Mexican standard (NOM-014-SSA1-1993). All the samples exceeded the maximum permissible limit established in the modified Mexican standard (NOM-127-SSA1-1994) of 1.5 mgL-1 for fluoride in water for human consumption. Average concentrations of 2.74 mgL-1 were found in Colonia San Jose, 2.19 mgL-1 in La Regina, 2.17 mgL-1 in Julimes and 2.06 mgL-1 in Hacienda Humboldt. Dental Fluorosis diagnosis was evaluated using the Dean Index and the CFI applied to residents. A total of 100 inhabitants were examined, with interviews and oral examinations also carried out. Dental Fluorosis prevalence was 92% overall for the municipality, while for Colonia San Jose was of 100%, of 88.89% for Hacienda Humboldt, 88.24% for Julimes and 96% for La Regina. Dental Fluorosis’ severity for the Julimes municipality was distributed as follows: 2% normal, 6% questionable, 8% very mild, 13% mild, 19% moderate, and 52% severe. An average CFI was found for the four localities of 3.02 points, with a very notable impact on public health.

High Fluoride, Modest Fluorosis: Investigation in Drinking Water Supply in Halaba (SNNPR, Ethiopia)

In Halaba district in Southern Ethiopia fluoride levels from boreholes are high (2.6 to 7.0 mg/l), yet the incidence of fluorosis is modest. Drinking water users living in the vicinity of four drinking water systems that have been in operation for more than 35 years were surveyed. Out of 625 persons 5 percent had severe dental fluorosis and 42 percent had mild forms—which is considerably less than results of other areas with comparable fluoride levels. The incidence was highest in the older age groups. Possible explanations were explored. A likely reason may be the continued large dependence on rain water harvesting ponds for human consumption alongside the use of water from the public borehole systems, but more investigations would be required to confirm this proposition.

Towards carbon neutrality of calcium carbide-based acetylene production with sustainable biomass resources

Acetylene is produced from the reaction between calcium carbide(CaC_(2))and water,while the production of CaC_(2) generates significant amount of carbon dioxide not only because it is an energy-intensive process but also the raw material for CaC_(2) synthesis is from coal.Here,a comprehensive biomass-to-acetylene process was constructed that integrated several units including biomass pyrolysis,oxygen-thermal CaC_(2) fabrication and calcium looping.For comparison,a coal-to-acetylene process was also established by using coal as feedstock.The carbon efficiency,energy efficiency and environmental impacts of the bio-based calcium carbide acetylene(BCCA)and coal-based calcium carbide acetylene(CCCA)processes were systematically analyzed.Moreover,the environmental impacts were further evaluated by applying thermal integration at system level and energy substitution in CaC_(2) furnace.Even though the BCCA process showed lower carbon efficiency and energy efficiency than that of the CCCA process,life cycle assessment demonstrated the BCCA(1.873 kgCO_(2eq) kg-prod^(-1))a lower carbon footprint process which is 0.366 kgCO_(2eq) kg-prod^(-1) lower compared to the CCCA process.With sustainable energy(biomass power)substitution in CaC_(2) furnace,an even lower GWP value of 1.377 kgCO_(2eq) kg-prod^(-1) can be achieved in BCCA process.This work performed a systematic analysis on integrating biomass into industrial acetylene production,and revealed the positive role of biomass as raw material(carbon)and energy supplier.