In this paper, a comparative study of the effectiveness of deep neural networks (DNNs) in the classification of pure and impure purees is conducted. Three different types of deep neural networks (DNNs)—the Gated Recurrent Unit (GRU), the Long Short Term Memory (LSTM), and the temporal convolutional network (TCN)—are employed for the detection of adulteration of strawberry purees. The Strawberry dataset, a time series spectroscopy dataset from the UCR time series classification repository, is utilized to evaluate the performance of different DNNs. Experimental results demonstrate that the TCN is able to obtain a higher classification accuracy than the GRU and LSTM. Moreover, the TCN achieves a new state-of-the-art classification accuracy on the Strawberry dataset. These results indicates the great potential of using the TCN for the detection of adulteration of fruit purees in the future. The adulteration of fruit purees or juices has long been a serious problem that needs to be carefully considered by manufacturers. This problem arises frequently out of two main reasons. On one hand, the adulteration of fruit purees or juices is profitable since certain fruits command premium prices. For instance, a variety of fruits, such as apple, raspberry, blackcurrant, blackberry, plum, cherry, apricot and grape, are usually used to adulterate strawberry purees. These fruit purees are always cheaper than strawberry purees and could be mixed with strawberry purees to make impure strawberry purees. Impure strawberry purees are then sold as pure strawberry purees for higher profits. On the other hand, the direct detection of the adulteration is quite difficult because of the nuance of flavor and color of pure and impure strawberry purees . To dealThe adulteration detection of fruit purees based on spectroscopy is a time series classification (TSC) problem of two classes: the authentic fruit and the adulterated fruit. Based on spectroscopy, various conventional algorithms have been employed for the adulteration detection of fruit purees. These methods include partial least square regression (PLS) , dynamicDuring the last few decades, deep neural networks (DNNs) have recently achieved great success in a number of time series modeling tasks ,12,13,14Motivated by the great success of DNNs, this paper first employs DNNs for the adulteration detection of fruit purees and provides a performance comparison of different DNNs. Three types of DNNs—GRU, LSTM, and TCN—are tested on the Strawberry dataset from the UCR time series classification repository . ExperimIn this section, the publicly accessible dataset, Strawberry dataset, from the UCR time series classification repository is first introduced. The training criterions, evaluation metrics, as well as the training descriptions of three deep neural networks for TSC are then described in detail. Next, the network structures of the GRU, the LSTM and the TCN for TSC are introduced in detail, respectively.The Strawberry dataset contains the mid-infrared spectra of 983 fruit purees, including strawberry purees and non-strawberry purees, such as apple purees and plum purees. This dataset is a time series classification dataset of two classes—strawberry samples and non-strawberry samples. This dataset has been obtained using Fourier transform infrared (FTIR) spectroscopy with attenuated total reflectance (ATR) sampling. Each sample in the Strawberry dataset is a one-dimensional time series of length 235. For all the DNNs, each time series sample of length 235 is fed into the model as a two-dimensional input of size 1 × 235. The statistics of the Strawberry dataset are shown in Given the true label The classification accuracy on the test dataset is used to evaluate the model performance. The formal definition of classification accuracy is shown in Equation (2),d, and the filter size, k, of the dilated causal convolution are The TCN in the experiment consists of six residual blocks. The dilation factors, In addition, the five-fold cross validation is conducted to find the optimal hyperparameters of all DNNs. Specifically, the output dropout rate varies in the set {0.0, 0.1, 0.2}. The optimal output dropout rate is selected based on the average classification accuracy on the five validation sub datasets. After the five-fold cross validation, the whole training dataset is used to train the DNNs with the best hyperparameters and the classification accuracies of all models are reported on the test dataset.Both GRU and LSTM are two popular variants of basic RNNs that incorporate gate units into the basic RNN cell to capture the long time dependency in the time series. In the GRU, two gate units, a reset gate TCN is a specially designed convolutional network for sequence modeling. Formally, given an input sequence itecture . In the itecture , rather olutions  to enablal block , which hAs shown in The training losses of the GRU, LSTM, TCN, and Multilayer Perceptron (MLP) are illustrated in From In this paper, a comparative study of DNNs for the classification of pure and impure strawberry purees was provided. Specifically, three different types of DNNs—GRU, LSTM, and TCN—were implemented for the detection of the adulteration of strawberry purees. These three models were tested on the Strawberry dataset from the UCR time series classification repository. Computational experiments indicated that the TCN obtained a higher classification accuracy than GRU, LSTM, and MLP. Also, in comparison to the best accuracy, 97.30%, obtained by the conventional algorithm RotF , the TCN


This paper presents the analysis of an intensity variation polymer optical fiber (POF)-based angle sensor performance, i.e., sensitivity, hysteresis and determination coefficient ( The biomechanics of human movement are defined as the study of the human movement using methods of mechanical engineering . The humOptical fiber sensors (OFS) present advantages such as being lightweight, compact, chemically stabile, immune to electromagnetic fields, and for their multiplexing capabilities . In addiAmong the optical fiber materials, polymer optical fibers (POF) provide a much lower cost alternative to other optical fibers, besides the high elastic strain limits, high fracture toughness, high flexibility in bending and high sensitivity to strain. Polymers also have biocompatibility, favoring the use for biomedical applications . For theTo maintain the low cost, simpler interrogation techniques are usually used, such as the intensity variation principle. However, this technique offers precision limitations, presenting low sensitivity and systematic errors, such as nonlinearity, offset and hysteresis , when coThe fabrication of POFs consists of a variety of optical polymers, including polymethyl-methacrylate (PMMA), cyclic transparent optical polymer , cyclic olefin copolymer (COC), polystyrene (PS) and polycarbonate (PC) ,19. PMMASince the polymers are viscoelastic materials, they do not have constant response to stress and strain, especially in dynamic loading conditions . The polThis paper presents the development, characterization and analysis of a lower limb multi joint angle POF-based sensor using CYTOP fiber and the proposal of an angular velocity compensation technique to reduce errors of the proposed sensor for gait application. Curvature tests were performed under different light source central wavelength and different angular velocities (within knee and ankle velocity range) in order to evaluate the sensor performance based on three parameters: sensitivity, hysteresis and determination coefficient  with a core diameter of 120 The sensor operation principle is based on intensity variation, in which the attenuation of the transmitted optical signal power is related to the bending angle of the fiber, i.e., the transmission loss occur due to radiation losses caused by macrobending and is proportional to the variance of optical fiber’s bending angle.The experimental protocol was divided into two approaches in order to evaluate the performance of the CYTOP fiber under curvature: influence of different light source central wavelengths and influence of different angular velocities. Both approaches consisted of curvature tests with angular range from S is the sensitivity, h is the hysteresis, In the first approach, curvature tests with angular velocity of Equation ) in ordeEquation , S is thThereafter, tests with different angular velocities  in different angular velocities see . In bothA Shapiro–Wilk test was used to verify the data normality. Since the data are normal, one-way ANOVA  was applied to determine if significant differences in sensitivity, hysteresis and angular error existed among different angular velocities with a significance level of To reduce the RMSE of angle measurements, compensation models were developed for each angular velocity group. P is the sensor power variation (ADC unit).Since the CYTOP is a viscoelastic material, its strain response depends on the time and the polymer relaxation can lead to the sensor hysteresis and possible variations on its linearity. To obtain a response close to the ideal (servo motor input), i.e., linear response, the compensation models were based on a sum of exponential with order 2, as shown in Equation (To verify the stability of the sensor material related to temperature and humidity variation, two tests were performed. One test consisted of the sensor response analysis with the temperature increase and the other test consisted of the sensor response analysis with the increase of relative humidity. The analysis of POF curvature sensor in CYTOP fiber is based on three performance factors: sensitivity, hysteresis and Thus, the sensor using LED with central wavelength of atasheet . Since tBased on these performance factors, a FoM was applied to calculate the weighted sum of the factors and to select the central wavelength that results the higher FoM. The weighted coefficients for FoM calculation were defined as echnique . Table 1After the first set of tests to select the light source central wavelength, tests with the angular range from According to In addition to angular errors, the sensor responses presented high RMSE with maximum mean of  6.45∘0.4∘. For thquations  relatingThe compensated responses presented a RMSE decrease up to v = v = The high errors of uncompensated responses are due to the variation of angular velocity, resulting in a different response from the characterization. When the angular velocity compensation was applied, according to the angular velocity of the curves, the response was more similar to the reference, with a decrease of This paper presented the performance analysis of a POF curvature sensor using CYTOP fiber under two conditions: different light source central wavelengths and different angular velocities. In addition, the sensor was applied on two approaches in the gait analysis: simulating knee and ankle patterns during the gait. The curvature sensor comprises of POF based on intensity variation principle, which present the lowest cost and highest simplicity in the fabrication and the signal processing. Results showed differences in sensitivity and hysteresis between light source central wavelengths, where best performance of


Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation. Vascular endothelial growth factor (VEGF) is a multi-functional factor primarily involved in the regulation of proliferation, differentiation and survival of endothelial cells as well as in vascular permeability . The famVEGFs exert their effects mainly through binding to tyrosine kinase receptors: fms-like tyrosine kinase 1 , kinase insert domain receptor , and Flt-4  ,11. BesiVEGF is implicated in a wide variety of physiological and pathological conditions. During the process of embryo development, VEGF participates in embryonic vasculogenesis and angiogenesis ,26. MoreEndometrium lines the inside of the uterus and undergoes cyclic breakdown and remodeling, which are accompanied with the reconstruction of the vascular system. During the menstrual cycle, there is only a short and critical period of time allowing an embryo to implant, when the endometrium becomes a well-vascularized tissue characterized by increased vascular permeability, oedema, and angiogenesis . AlthougExtensive efforts have been made to explore the spatial and temporal expression change of VEGF in the endometrium across the menstrual cycle. Several studies have found the expression of VEGF in the endometrium throughout the menstrual cycle, with a significant increase in the mid-luteal phase, suggesting a role of endometrial VEGF around the time of embryo implantation ,35,36. IIn accordance with the upregulation of VEGF, VEGFR-1 and VEGFR-2 are also upregulated in the glandular epithelium in the secretory phase . sFlt-1,Histochemistry staining reported that PlGF, which exists in glandular and luminal epithelial cells, decidual stromal cells, and uterine fluid, showed increased staining intensity in the endometrium around the time of embryo implantation . Santi eIt is worth noting that besides an angiogenic effect, VEGF and PlGF are also functionally related to immune regulation. An embryo is an allograft to the maternal immune system, and immunologic tolerance is critical for the successful establishment of embryo implantation. During the establishment of immuno-tolerance, numerous immunosuppressive mechanisms and various immunocytes, including uterine natural killer (uNK) cells, macrophages, and dendritic cells, are thought to play significant roles ,51. SeveThe growth and development of follicles are dependent on an adequate blood supply to obtain nutrients and oxygen. Insufficient blood supply could lead to a low-oxygen status in follicular fluid and severely disrupt the development of oocytes and, subsequently, of the embryo . The inhVEGF also acts in the formation and function of corpus luteum . Corpus With a highest level during the periovulatory period, VEGF shows dynamic changes in the human oviduct across the menstrual cycle and is thought to be implicated in the secretion of oviductal fluid via regulating the vascular permeability of the oviduct  65,66].,66.65,66VEGF can be detected throughout the process of embryo development ,83. The After an embryo enters the uterus lumen, the interaction between embryo and endometrium starts in the uterine fluid through locally produced soluble mediators. Uterine fluid, also called uterine secretion, is mainly produced by uterine glands. During the peri-implantation period, endometrial glands secrete important mediators that facilitate pre-implantation embryo development and embryo implantation. Several VEGF family members such as VEGF and PlGF have been identified in uterine fluid ,47. It iFurthermore, VEGFR-2 could interact with integrin αvβ3 , which iRIF occurs when a woman under the age of 40 fails to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen embryo transfer cycles . There aOne earlier study has reported an increased serum VEGF level in women with RIF compared to fertile controls , whereasRM is defined as three or more consecutive miscarriages before 24 weeks of gestation . AlthougLash et al. explored the expression of VEGF and its receptors in women with unexplained recurrent miscarriage . The resIn addition to the endometrial tissues, there are also some studies focusing on VEGF expression in other types of tissue from women with recurrent miscarriage. By sampling chorionic villi from RM patients, Pang et al. found that VEGF and sFlt-1 levels were increased when compared to their levels in women with a normal pregnancy . HoweverAlthough there is compelling evidence showing dysregulation of VEGF in a number of common diseases, the underlying causes of this dysregulation remain unknown. Genetic variation might be one of the potential causes responsible for dysregulated VEGF expression . A meta-Endometriosis is a common cause of infertility in women of reproductive age. There is accumulating evidence showing that eutopic endometrium in women with endometriosis displays higher VEGF expression ,113. At PCOS is a common endocrine disease characterized by oligomenorrhea or amenorrhea, hyperandrogenism, and the presence of polycystic ovary. In addition to endocrine disorders, ovarian hyperplasia and hypervascularity are also two common features of PCOS and are thought to be related to extensive angiogenesis of the ovary ,119. TheIt has been proved that VEGF levels in serum and follicular fluid of PCOS patients were significantly higher, while sFlt-1 level was lower than in normal ovulatory women ,126. TakPE is a serious pregnancy complication characterized with hypertension and proteinuria. A defect in placental angiogenesis is considered to be one of the factors responsible for the pathogenesis of PE . SignifisFlt-1 was found to be upregulated ,133,134,Based on the fact that the process of angiogenesis is regulated by numerous pro-angiogenic and anti-angiogenic factors and cytokines as well as angiogenic receptors, there is an increasing number of studies focusing on the balance between pro-angiogenic and anti-angiogenic factors in preeclampsia ,144. In Over these years, the development of anti-VEGF agents has achieved great progress ,147. A nVEGF is an important angiogenic factor in many physiological and pathological conditions. In this review, we summarized recent data on the role of VEGF in embryo implantation and reproductive failure. The existing data show that VEGF plays multifaceted roles in embryo implantation and that the alteration of the expression of VEGF, including VEGF polymorphisms, could lead to infertility and pregnancy complications. However, little is known about the mechanisms whereby VEGF influences embryo implantation or the root causes of the observed alterations in VEGF expression. Further studies are in urgent need to clarify the role of VEGF in successful pregnancy and reproductive failure.


Microbes colonize the human body during the first moments of life and coexist with the host throughout the lifespan. Intestinal microbiota and their metabolites aid in the programming of important bodily systems such as the immune and the central nervous system during critical temporal windows of development, with possible structural and functional implications throughout the lifespan. These critical developmental windows perinatally (during the first 1000 days) are susceptible timepoints for insults that can endure long lasting effects on the microbiota-gut-brain axis. Environmental and parental factors like host genetics, mental health, nutrition, delivery and feeding mode, exposure to antibiotics, immune activation and microbiota composition antenatally, are all factors that are able to modulate the microbiota composition of mother and infant and may thus regulate important bodily functions. Among all these factors, early life nutrition plays a pivotal role in perinatal programming and in the modulation of offspring microbiota from birth throughout lifespan. This review aims to present current data on the impact of early life nutrition and microbiota priming of important bodily systems and all the factors influencing the microbial coexistence with the host during early life development. Starting from the first moments of life, the human body is colonized by a wide variety of microorganisms ,2 that cThe microbiota has been found to influence not only at a local level with respect to the intestinal microenvironment but also beyond the GI tract, implicating the physiological and structural aspects of the central nervous system (CNS). The communication pathways which enable the interaction of intestinal microbiota with the CNS of the host is described as the microbiota-gut-brain axis ,8,9,10. To date, the majority of data on the microbiota-gut-brain axis has been gathered from studies using animal model systems. Indeed, various germ-free (GF) animal studies have shown that lifelong absence of microbiota not only alters gut physiological functions, but also the behaviour of those animals ,17,18. SDespite intensive investigations, the mechanisms underlying the communication pathways between intestinal microbial systems and the host remains rather elusive. Moreover, the full implication of such interactions on health and disease in critical temporal windows across the lifespan are still being unravelled. The impact of early life nutrition on the composition of the gut microbiota, the microbiota-mediated priming of CNS and immune system and the response of the host during this crosstalk is intricate and complex. The aim of this review is to summarize recent knowledge and highlight the effects of early life nutrition on the gut-brain axis development, the shaping and maturation of the intestinal microbiota and the dialogue among these stakeholders during critical periods of neurodevelopment.Homeostasis of the intestinal microbial environment is likely to be affected multiple times across the lifespan of the average individual due to antibiotic usage , inflammDespite the underlying mechanisms of the intercommunication along the microbiota-gut-brain axis remain incompletely understood, there is a variety of potential trajectories , which include acetate, butyrate and propionate . These mde novo synthesized in our body to modulate and support early life development. There are multiple nutrients with epigenetic potential that are present in the diet or produced via microbial metabolism in the human gut [Nutrition holds a central role in the early life maturation of many tissues within the body, with both short- and long-term effects on development of the infant, in an organ-, time- and intervention-dependent fashion, which is called nutritional programming . Nutritiuman gut . B compluman gut .These sensitive time-periods are temporal windows of developmental opportunity that, if missed, alterations in growth and normal functions of body systems are irreversible ,57. Thesde novo folate as a secondary molecule of their metabolism [Parental nutrition and health status prior to conception are crucial for the appropriate structural development of the CNS of the offspring see . Certaintabolism . Furthertabolism ,67, thusIncreasing research suggests that environmental influence on parental health can modulate functional aspects of infant development, such as offspring’s behaviour later in life ,69. ReceExpanding data point to the existence of critical temporal windows before conception, regarding parental nutrition and microbial metabolites shaping the immune system of the offspring ,73,74,75The brain is subjected to multiple structural and functional, time-specific changes during gestation such as axonal growth , synapseMaternal nutrition during pregnancy can modulate some of the multiple structural and functional changes that are happening in the offspring brain perinatally . In factNutrient deficiencies in the mother during pregnancy may result in abnormal neurodevelopment of the fetus, in humans, which leads to related adversities in the adult offspring ,86. For Dietary habits during the period of gestation can shape the maternal intestinal microbiota ,89 whichBifidobacterium group in babies of overweight mothers compared to babies born to normo-weight mothers [Bifidobacterium on weight development and weight control of the infant.Maternal weight and obesity have been associated with alteration in composition of the gut microbiota, with obese individuals displaying altered microbial profiles compared to normo-weight individuals . Microbi mothers  emphasizBacteroides have been found in neonatal meconium samples from infants with mothers exposed to a diet with increased fat content (>40% of daily intake) during pregnancy, with those low levels of Bacteroides persisted until 6 weeks of age [Bacteroides genus, part of the commensal bacteria in the gut, is present in low amounts in the infant gut right after birth and it becomes gradually more abundant after solid food introduction [Bacteroides in adulthood have been previously associated with obesity and altered metabolic capability of the host [In a cohort of Hispanic mother-infant pairs, low levels of s of age . The Bacoduction . Low couthe host .Lactobacillusreuteri, Bifidobacterium pseudolongum and Bacteroides uniformis present in the faeces of pups originating from dams exposed to HFD compared with pups originating from dams exposed to normal chow diet (13.4% of daily intake) [In preclinical studies, maternal dietary manipulations during pregnancy can modify the offspring microbiota composition . For ins intake) . Additio intake) . Moreove intake) , probablApart from maternal nutrition during pregnancy, there are other factors modulating the offspring’s intestinal microbiota composition in early life such as mode of delivery, type and duration of feeding see  which arThe composition of the maternal gut microbiota varies dramatically in response to hormonal, immunological and metabolic changes that take place during pregnancy . It is kFor the past decade, scientists examined controversial data regarding the possibility of a non-sterile environment during the course of gestation ,101,102.The assembly of fetal neuronal circuits can be perturbed in response to maternal and environmental microbial disruptions during pregnancy. Recent data suggest that depletion and partial reconstitution of the maternal microbiota during pregnancy modulate fetal thalamocortical neurodevelopment in rodents -via transplacental metabolic signals-which is linked to sensorimotor behaviour and pain perception postnatally . AdditioToday it is understood that the initial microbiota inoculation begins at birth while the fetus passes through the birth canal and is exposed to maternal vaginal and faecal microbiota . This coBifidobacterium, Lactobacillus and Bacteroides [Staphylococcus [During Caesarean-section (C-section) the infant is not exposed to the maternal vaginal and faecal microbiota and the vertical transmission is disrupted . Interesteroides ,115, andHowever, emergency C-section impacts the microbiota differently compared with elective C-section, due to the fact that the neonate is partly exposed to the birth canal in the early stages of labour ,117,118.Mode of delivery is a strong modifier of the relationship between maternal perinatal nutrition and postnatal infant microbiota composition development . In a clAlthough mode of delivery has a widely known impact on the new-born microbiota, its exact influence on microbiota shaping throughout the lifespan is still rather controversial due to confounding factors  . Even thC. Difficile [Ways of modulating gut microbiota such as faecal microbiota transplantation (FMT) in both clinical and preclinical context, are being studied. It is evident that microbiota interventions like FMT could reinstate gut microbiota composition of individuals with clinical or subclinical intestinal conditions such as diarrhoea, IBD and intestinal infections. . Most stifficile . The conifficile . The FMTifficile . Future Most developmental studies investigating the mode of delivery focus on bacteria but, recently scientists are shifting their interest on the effect of birth mode to the gut virome (the assemblage of viruses present in the intestine) and phageome (the bacteriophage community present in the intestine) ,126 whicEarly life disruption of microbiota by C-section has been associated with some well-known disorders in childhood and adulthood. In clinical studies, C-section has been correlated with immune disorders including asthma and allergies ,128,129,It could be hypothesized that behavioural effects due to differential microbial colonization as a result of C-section, are possibly extended to later stages of life, affecting multiple aspects of social behaviour. However, more studies are needed to investigate the long-term microbiota changes and behavioural effects of delivery mode, with shifting focus to the missing microbes in C-section delivered individuals. Targeting the behavioural effects with probiotic intervention strategies to potentially rescue behavioural deficits is a rather promising avenue for those individuals.The brain is highly metabolically active in early life and its energy expenditure accounts for half of the total daily resting energy metabolism . At fullBifidobacterium, that are also highly abundant among the commensals in the maternal breast milk. The offspring gut microbiota modulates multiple levels of development, almost immediately following birth. For instance, certain bacteria have been shown to stimulate gene expression of tight junctions in mice, boosting the closure of the gaps between epithelial cells and promoting gut barrier maturation postnatally, that is known to be immature in the early steps of life [Bifidobacteria have been found to boost gut barrier function, and improve intestinal disease outcome by decreasing the intestinal permeability in rodents [Bifidobacterium can alter structural characteristics of the CNS and modify neurodevelopment in early postnatal life by promoting synaptic formation and microglial function postnatally [Bifidobacterium in regulating multiple aspects of development following microbial colonization at birth.The new-born gut is mainly colonized by various species of  of life . In the  rodents . In prectnatally , while itnatally ,143. ColSoon after birth, microbiota in the infant gut is nurtured and shaped by the dietary and bioactive components of milk that are discussed below  cause changes in human milk composition. Breast milk of mothers with premature delivery contained significantly higher amounts of protein and immunological components compared to milk from full-term mothers . InteresHuman milk composition is dynamic, varies within a feeding, diurnally, over the different stages of lactation, and between mothers . Breast Breast milk is composed of a distinct combination of constituents that leads to specific metabolic and physiological responses in children, regulating intestinal function, immunity and brain development . The comMacronutrient composition of breast milk varies within mothers and across lactation and it highly depends on maternal diet . HoweverMultiple bioactive milk components have been found to modulate the immune system via gut microbiota ,164, enhMilk fat globules (MFG) are lipid droplets surrounded by a phospholipid tri-layer and are secreted locally by the mammary lactocytes ,189. TheThe lipid to protein weight ratio in MFGM is approximately 1:1, highlighting the protein presence at the MFGM . Among mThe MFGM in human milk has been linked to cognitive and health benefits in humans  and rodeBifidobacterium infantis has a very specific preference to metabolize lacto-N-tetraose, but is also able to grow sufficiently in other HMOs [Bacteroides have been found to digest only specific types of HMOs in vitro [Human milk oligosaccharides (HMOs) such as 2-fucosyllactose and lacto-N-tetraose, are indigestible glycans that pass through the GI tract. HMOs composition is affected by maternal characteristics such as maternal BMI and geography , geneticher HMOs , while vin vitro . Therefoin vitro .Bifidobacterium in the intestine, a genus that is abundant in the gut of breastfed infants [Salmonella, Listeria, and Campylobacter, by preventing those pathogens from attaching to the intestinal wall, hence forcing them to be excreted from the GI tract [More than 200 separate types of HMOs are present in maternal milk which have a protective action on the infant gut. They induce maturation of epithelial cells and improve gut barrier function, protecting the infant gut from infections and, promoting the viability and diversity of commensals . A few c infants ,206,207.GI tract .HMOs’ action can also improve infant health and neurodevelopment via microbiota-gut-brain axis. It has been recently suggested that there is a link between 2-fucosyllactose consumption, frequency of breastfeeding and cognitive development in 1-month old breastfed infants . MoreoveHMO-associated sialic acid is another bioactive component of breast milk, that is more abundant in the early stages of lactation compared to term milk ,213. SiaBifidobacterium and Bacteroides genera, compared to formula-fed infants [Even though breast milk was initially considered sterile, microbial metabolites were detected in the colostrum, which is the first milk produced after birth . Intesti infants ,223,224. infants .Actinomyces, Bifidobacterium and Lactobacillus) are not present in the neonatal oral cavity before the onset of breastfeeding [Bifidobacterium longum, Bifidobacterium pseudocatenulatum and Streptococcus thermophilus in maternal stool, maternal blood, breast milk and infant stool samples highlighting the maternal-breast milk-infant link in the onset of infant microbiota [Various mechanisms have been proposed for microbiota transmission via breastfeeding such as (1) contact with maternal skin, (2) retrograde flow from the infant oral cavity to the ductal tissue and (3) enteromammary trafficking . In ordetfeeding . Therefotfeeding . Additiotfeeding . The thitfeeding . Genomiccrobiota ,228,229.crobiota .Lactobacilli, Staphylococci, Streptococci and Bifidobacteria [Breast milk has a dynamic microbial assembly composed of mammary skin-, maternal gut- and neonatal oral-associated viable microorganisms with more than 200 different genera present , includibacteria ,225,230.bacteria ,231,232.Lactobacilli compared to Western diet, in the mammary glands of a non-human primate model [For instance, a maternal Mediterranean diet led to increased abundance of te model . In anotte model . These ate model .As long as breastfeeding is maintained, breast milk microbiota is an endless supply of colonizing bacteria for the infant gut and exert their effects via the gut-brain axis on modulation of intestinal, neurological and behavioural functions in early life that could possibly imprint the CNS and immune system throughout the lifespan ,121,233.Infant formula is a manufactured food designed for feeding children under 12 months of age. There are multiple reasons why infant formula feeding is a necessary alternative such as inability to breastfeed due to health issues or socioeconomic reasons . However, infant formula feeding is not recommended unless there is no other alternative, with breastfeeding being the first choice and breast milk from donors following in second place . Infant The macronutrient composition of infant formula has changed rapidly over the last decade. The majority of the constituent protein is derived from bovine milk, which is generally lower in quality compared to human milk proteins, primarily due to the limited amount of essential amino acids present in bovine milk . The proBifidobacterium, contrary to the HMOs present in human milk that are only partly metabolized by this genus [Health benefits of HMOs present in human milk on the intestine, the diversity of commensals, the immune and the central nervous systems incentivised infant formula-producing companies to supplement formulas with prebiotics in order to narrow the gap between human milk and infant formula . Prebiotis genus . Two othis genus . Consumpis genus , but thiis genus .Bifidobacterium [Lactobacillus [Escherichia coli, Enterococcus and Clostridium) was evident in faecal samples of 3-month-old infants receiving prebiotic supplemented infant formula compared to infants that received non-supplemented one [Prebiotic supplementation of infant formula led to significantly altered microbiota composition in infants compared to non-supplemented control infant formula  and has acterium ,247 and nted one ,245. Supnted one ,248.Bifidobacterium and Lactobacillus strains), have been developed in order to create infant formula as close as possible to human milk [In order to maximize the advantages of prebiotics, combined prebiotic mixtures with different genera of bacteria  is an intricate process which has difficulty in mirroring the unique combination and complexity of ingredients present in breast milk ,249. Thebacillus  , overweight and obesity and remains a global health challenge up until today . Apart fThe nutrient availability for the developing fetus depends on the concentration of those nutrients in maternal circulation and the blood flow in the placenta that will distribute them to the embryo . After bDuring pregnancy, even mild or moderate caloric restriction could have a dramatic impact on the fate of CNS development. In a non-human primate model, moderate caloric restriction in the mother led to decreased cerebral development, neurotrophic factor suppression, impaired axonal growth and glial maturation in the offspring . In the BDNF gene expression levels in the hippocampus of the offspring accompanied by impaired spatial learning and memory [In rodents, reduced maternal protein intake during pregnancy (5 or 10% protein as compared to 20% protein) caused not only impairments in brain development and growth rate of the pups, but also in protein and fatty acid metabolism, in the brain and on a whole-body level . In anotd memory . Moderatd memory , and gend memory .In humans, insufficient early life energy, protein iron and iodine intake leads to impaired behavioural and cognitive function that persist to adulthood. Deficiency of B vitamins, zinc, betaine and choline are able to induce irreversible changes in the brain and lead to neurological deficits on the developing child ,276. DurOptimal nutrition in early life is crucial for the expansion of the microbiota, immune system development, and the balance of host-microbe interactions. Exposure of 3-week-old mice to reduced dietary protein resulted in decreased binding of intestinal immunoglobulin A (IgA) with commensal bacteria, interfering with normal mucosal processes in the mouse intestine . This diSalmonella, Shigella and Staphylococcus aureus populations in faecal samples [In severely malnourished children it is difficult to identify whether the changes in gut microbiota composition present as a consequence of the diet or the condition or the combination of both . A commo samples . These b samples .Bifidobacterium and an inverted aerobes:anaerobes ratio in faecal samples resembling a non-mature microbiota [Lactobacillus delbrueckii effectively reduced mortality of malnourished children [Microbiota composition in malnourished children is disturbed with almost depleted crobiota ,281. Nutcrobiota . Antibiochildren . The comchildren .Recent approaches have focused on targeting the microbiome for undernourished children via societal strategies such as educational support highlighting the importance of the microbiota on high-risk communities  and promPoverty and food insecurity are major risk factors for malnutrition . HoweverMicrobes are co-existing and co-evolving with humans across the lifespan and it is believed that the beginning of this mutualistic relationship starts at birth. However, increasing data has shown that microbial signatures modulate embryonic development, imprint the CNS and the immune system and fine-tune the balance between health and disease. Both neurodevelopment and microbial composition in early life are plastic and influenced by parental  and environmental  factors.Early life nutrition plays a central role in the onset of multiple developmental processes in the brain and the alimentary canal via nutritional programming and modulation of the microbiota-gut-brain axis during the first steps of life, regulating the equilibrium between health and disease later in life. Understanding the link between the triad of perinatal nutrition, neurodevelopment and gut microbiota is of great importance in order to unravel the mechanisms of diseases that are believed to be rooted in early life. Although important data has recently described some of the early life nutritional programming and the microbial contribution on the imprinting of the CNS, principal mechanisms remain elusive. Perturbations that challenge the balance of this relationship during critical temporal windows of development might disturb gut homeostasis and host-microbial interactions, as well as structural and functional alterations in the CNS. More research is essential on the impact of nutrition on the shaping of the gut microbiota and neurodevelopment of the offspring to untangle the intertwined pieces of this complex puzzle that is microbiota-gut-brain axis and, to possibly prevent, diagnose and mitigate conditions that are rooted in this sensitive period.


Obesity is a rapidly growing public health threat in China. Improvement of dietary knowledge may potentially reduce the risk of obesity and being overweight. However, existing studies focus on measuring the mean effects of nutrition knowledge on body mass index (BMI). There is a lack of literature on the effect of dietary knowledge on BMI, and the potential heterogeneity of the effect across the whole BMI distribution and across socioeconomic status (SES) groups. This study aims to investigate the heterogeneous nature of the relationship between dietary knowledge, SES, and BMI, using data from the China Health and Nutrition Survey (CHNS) in 2015. We employed unconditional quantile regression (UQR) to assess how the relationship between dietary knowledge, SES, and BMI varies across the whole BMI distribution, and conducted subgroup analyses using different socio-economic subsamples. Results indicate that dietary knowledge had no statistically significant impact on BMI across the BMI distribution. There was a large degree of heterogeneity in the SES effect across the BMI distribution as well as a major gender difference in the SES effect on BMI. Education had a significant and inverse association with BMI across the BMI distribution, greater at higher BMI quantiles. Income growth had a larger effect on the 50th quantile of BMI for males in the middle-income group, but was not significant for females. As income increased, males without college educations had higher BMI while females with college or higher education generally had lower BMI. The findings of this study reveal the heterogeneous nature of the relationship between SES, gender, and obesity across the entire BMI distribution, suggesting that quantile regressions might offer a valuable framework for exploring the complex relationship of dietary knowledge, demographic, and socio-economic factors on obesity. Obesity is a major public health problem and the fifth leading cause of death globally . WorldwiChina had the largest obese population in the world in 2014 . The preIt is believed that nutrition knowledge is one of the important factors for healthy diet . AccordiPrevious research exploring the relationship between nutrition knowledge and body mass index (BMI) showed mixed results. Some studies done among Belgian women, urban men in France, children in Germany, adolescents in the US, and urban adults in Northern Ireland did not demonstrate significant association between nutrition knowledge and BMI ,15,16,17Existing studies primarily focus on the average effect of nutrition knowledge on adult BMI, but do not investigate possible non-linear relationships or heterogenous effects of nutrition knowledge on obesity across the distribution of BMI, or across subgroups defined by certain demographic and socioeconomic characteristics, such as gender, income, and education. Gender-specific associations between education and income in relation to obesity have been reported . Income Although nutrition knowledge and dietary knowledge both emphasize the importance of healthy eating, the former focuses on detailed nutrient intake and its linkage to diseases, while the latter stresses the importance of balancing diet and exercise . StudiesIn this study, we used the data from the China Health and Nutrition Survey (CHNS), designed to examine the effects of health policies and programs on the health and nutritional status of the Chinese population . This on2). It is adopted by the World Health Organization (WHO) to classify being overweight and obesity. BMI provides the most useful population-level measure of obesity and being overweight; by far it is also the most commonly used method for determining obesity [Dependent variable: Obesity is defined as the excessive accumulation of body fat, and can be measured by different indexes such as waist-to-hip ratio (WHR) and BMI. The BMI is defined as the weight in kilograms divided by the square of the height in meters  factors: income, education, age, gender, household size, marital status, and regional variables [ariables ,35,36,37ariables . Based oDescriptive statistics were generated for the dependent and independent variables of the study respondents and presented in µ) as well to control for the unobservable regional factors.The whole study sample included 9901 respondents, after excluding observations with missing values and respondents who were 18 years old and younger. To examine the relationship between dietary knowledge, SES, and BMI among Chinese adults, unconditional quantile regression (UQR) models were used, where BMI was the dependent (or effect) variable and dietary knowledge, and SES were the independent (or explanatory) variables . All modQuantile regression, including UQR and conditional quantile regression (CQR), has a fundamental advantage over the ordinary least squares (OLS) estimation ,29, whicUQR is based on extending the concept of the influence function to what has been termed the recent influence function (RIF), defined as follows:After recalculating the variables of interest, Equation (2) can be estimated by the OLS:R denotes the fixed effects capturing the unobservable factors that may affect the BMI, iDK, i,SES and iDE denote dietary knowledge,ith respondent, respectively, An expression illustrating BMI as a function of a set of independent variables can be written as follows:The linear functional form of Equation (3) used in our data analyses can be written as follows:The coefficient estimates of the UQR model specified in Equation (4) were obtained using RIF regressions at the quantiles of the BMI distribution . The coeWe performed the UQR analysis using the whole study sample of all 9901 respondents and also conducted subgroup analyses to explore how the relationship between dietary knowledge, SES and BMI varied across different socio-economic subgroups. Subgroups were defined by income levels, i.e., low-income group, middle-income group and high-income group, and by education levels, i.e., low-education group (below college) and high-education group (college and above), respectively. The subgroup analyses evaluated the relationship between BMI and dietary knowledge and SES in each specific subsample, enabling us to identify the potential subgroups of respondents who had stronger associations between dietary knowledge, SES and BMI.To examine the robustness of our results, we used two different income variables, the household income per capita and the total household income, respectively, in the UQR model specified in Equation (4) and compared their results. In this analysis, we used the whole study sample of all 9901 respondents. The estimated coefficients of Equation (4) obtained using UQR and the OLS are presented in Income was significantly related to higher BMI at almost all percentiles of the BMI distribution. For both females and males, as income level increased, the marginal effects of income on BMI showed a decreasing trend. However, there was a significant gender difference in the effect of income on BMI. For males, income was significantly related to higher BMI at most percentiles of the BMI distribution, while for females, the estimated coefficients became negative and statistically insignificant for the mean effect and some quantiles .Marital status was not significant for BMI at all quantiles of the BMI distribution although the OLS estimates showed that married individuals had higher mean BMI than unmarried individuals. Rural residency was not significantly associated with BMI at almost all quantiles, and household size had no significant relationship with BMI at all quantiles.Education had a significant and inverse relationship with BMI at all quantiles, and the effects of education on BMI became greater at higher BMI quantiles. Smoking was significantly and inversely associated with BMI across the whole BMI distribution. Alcohol intake had a significant association with BMI almost at all BMI quantiles except for the lower levels .p < 10%).The age variables remained statistically significant for BMI at most BMI quantiles in all three income groups. In the middle-income and the high-income groups, difference between males and females at the 50th quantile of BMI was significant while it was not significant in the low-income group. Similar to the results from the whole study sample, rural or urban residency and marital status had no significant effects on BMI at all quantiles in all three groups, except that marital status was significant at the 90th BMI quantile in the low-income group. Smoking had significant associations with low-income and high-income obese respondents, while for the middle-income group, it was significant only at the 10th BMI quantile. Alcohol intake had a significant association with BMI at the 10th to 50th quantiles in the middle-income group while it was significant at the 40th to 80th quantiles of BMI in both middle-income and high-income groups.We conducted subgroup analysis using the low-education group (below college) and the high-education group (college and above), respectively. Results in Improving dietary knowledge may potentially control the rising prevalence of obesity. Using the large-scale CHNS data from 2015, we carried out a comprehensive investigation of the complex relationship between dietary knowledge, SES, and BMI among Chinese adults. We employed the UQR technique and examined how the relationship between dietary knowledge, SES, and BMI varied across the entire BMI distribution, and across different socioeconomic subgroups, categorized by income and education levels, respectively. Results for dietary knowledge remained similar in both subgroup analyses; and generally, more factors showed heterogeneous results across the different education groups than across the different income groups. The study found that dietary knowledge had no statistically significant effect on BMI across the BMI distribution, confirming previous findings . One of Consistent with the literature, we found Chinese females tended to have statistically significant lower BMI than males . In addiThis study confirms previous findings that Chinese middle-class may suffer high risk for overweight and obesity . Income Our study found that higher education was significantly associated with reduced obesity risk, and there was a major gender difference in this relationship. As income increased, males without a college education were prone to obesity, while income had no significant effect on BMI for males with college (and above) education. In contrast, income increases had no significant effect on BMI for females without a college education, but BMI was generally lower for females with at least a college education. A possible explanation might be that women with higher education are more likely to have a higher SES, more health knowledge, and better access to more healthy resources, and consequently live healthier lifestyles . AnotherConsistent with previous studies, we found drinking and smoking were significantly associated with BMI. Cigarette smoking was negatively associated with BMI across the BMI distribution while alcohol intake had a positive relationship with BMI at most percentiles of BMI (30th percentile and higher). The negative relationship between smoking and BMI was well recognized ,37,40. AThis study has some limitations. Firstly, we used cross-sectional data rather than longitudinal data. There may be temporal effects of factors on BMI over time. Prospective longitudinal studies are warranted to investigate the risk factors that may contribute to the development of obesity among Chinese adults. Secondly, according to the existing literature, BMI may be also associated with genetic factors, which this paper did not examine due to data constraints . NeverthUsing the large-scale CHNS data and the UQR approach, this study investigated the complex relationship between dietary knowledge, SES, and BMI among Chinese adults. Our results provide further evidence that dietary knowledge had no significant impact on BMI across the BMI distribution. There was a large degree of heterogeneity in the SES effect across the BMI distribution, as well as a major gender difference in the SES effect on BMI. Education had a significant and inverse association with BMI across the BMI distribution, which was greater at higher BMI quantiles. Income growth had a greater effect on the 50th quantile of BMI for males in the middle-income group, but was insignificant for females. Males without college educations had higher BMI as income increased, while females with high education generally had lower BMI. The findings of this study show the heterogeneous nature of the relationship between SES, gender, and obesity across the entire BMI distribution.These findings may have public health significance. Our study suggests that it is important to consider the obesity risk of low-income people in the development of poverty alleviation strategies in China. Furthermore, we recommend that future dietary educational and promotional programs provide targeted strategies and guidelines suitable for individuals with different SES background. In addition, dietary education alone, albeit necessary, is insufficient to facilitate behavior change. In combination with dietary education, practical strategies are needed to motivate and facilitate dietary behavior changes. Moreover, individuals must also be aware of the consequences of their decisions, on whether or not to modify their dietary behaviors.The intermediate mechanisms through which dietary knowledge affects obesity are still largely unknown and are warranted for future studies.


Based on the results of an extensive literature research, we summarize the research progress of remote sensing monitoring in terms of identifying mining area boundaries and monitoring land use or land cover changes of mining areas. We also analyze the application of remote sensing in monitoring the biodiversity, landscape structure, vegetation change, soil environment, surface runoff conditions, and the atmospheric environment in mining areas and predict the prospects of remote sensing in monitoring the ecological environment in mining areas. Based on the results, the accurate classification of land use or land cover and the accurate extraction of environmental factors are the basis for remote sensing monitoring of the ecological environment in mining areas. In terms of the extraction of ecological factors, vegetation extraction is relatively advanced in contrast to the extraction of animal and microbial data. For the monitoring of environmental conditions of mining areas, sophisticated methods are available to identify pollution levels of vegetation and to accurately monitor soil quality. However, the methods for water and air pollution monitoring in mining areas still need to be improved. These limitations considerably impede the application of remote sensing monitoring in mining areas. The solving of these problems depends on the progress of multi-source remote sensing data and stereoscopic monitoring techniques. Mining areas are hotspots for the exploration and use of mineral resources and, subsequently, for the deterioration of the natural environment, characterized by conflicts between economic development and environmental protection ,2. SinceMining activities considerably damage the ecological environment, including landscape damage, vegetation damage, agriculture impairment, metal particle deposition, soil erosion, soil pollution, surface runoff, groundwater pollution, air pollution, and waste accumulation ,5, with In mining fields, early remote sensing is mainly applied in mineral exploration ,10,11, gAlthough some studies have monitored the ecological environment of mining areas via remote sensing, only a few publications have focused on combining these studies systematically. In this context, based on an extensive literature research, we summarize the research progress in terms of the identification of mining boundaries and land use or land cover changes as well as the monitoring of the ecological environment in mining areas based on remote sensing technology. Our overall aim is to identify the main issues of the current remote sensing technology and to predict the future development direction of this technology.The ecological environment of mining areas is complex, with numerous ground feature types, such as vegetation, dumps, water bodies, and tailing ponds, among others. Therefore, the accurate identification of the mining area scope and the precise extraction of various ground features and their changes are the foundation for remote sensing monitoring of the ecological environment in such areas . The useTraditionally, the boundaries of mining areas are determined based on the mining area scope specified by the mining license. According to the given coordinates of inflection points, the mining area scope can be formed by connecting these points. However, along with the prospection, exploration, and exhaustion of mineral resources, the specified scope of the mining areas may exceed or be less than the permitted scope. In this sense, the identifying the changes in mining boundaries is particularly important for studying the environmental impacts of mining activities. Identifying the boundaries of mining areas via remote sensing can provide a referenced study area boundary for environmental change assessment in mining areas ,20. In tCurrently, the identification of mining boundaries often adopts relatively mature extraction methods of remote sensing information and combines them with the ground feature environment and ground surface settlement characteristics of mining areas to extract the mining area boundaries . AccordiAt present, most remote sensing data for mining area boundary identification are derived from the Landsat series of the United States, and the spatial resolution of 30 m facilitates the acquisition of information of large mining areas or mining-intensive areas ,23,24. TIdentifying the changes in mining area boundary based on time series data is generally closely related to the land use changes in such areas. The change of either party can produce linkage reactions, especially when the scope of mining rights is not updated in time. This is also helpful to understand the relationship between boundary identification and ground feature type transformation, facilitating the accurate division of mining areas and the correct evaluation of the ecological environment.With changes in mining activities, the land use/cover of mining areas often changes dramatically. Therefore, investigating the land use/cover changes in mining areas is also one important research aspect related to the remote sensing identification of mining area factors. The important land use/cover types in mining areas generally include stopes, subsidence areas, tailing ponds, water areas, and bare land. Remote sensing identification and classification of water areas, bare soil, and slurry tailings discharged after ore washing in mining areas are complex and difficult to perform without prior knowledge. In addition, the continuous mining of underground and open pit mines may affect the vegetation within the mining scope and even reshape the local geological topography. Hence, “multidate” land use data of mining areas are important for evaluating the land resource changes and the ecological status of mining areas.The periods with the most significant land use/cover changes in mining areas include the initial period of mining activities and the period of resource exhaustion ,31. LandExtracting the ground features of mining areas via the remote sensing index is also a common method to analyze land use changes. The relevant indices of construction land , bare land (bare soil vegetation index), water area , and green vegetation  are all relatively advanced ,37,38, aThe balance and stability of the ecological state is an important prerequisite for the sustainable development of mining areas, and an intact ecosystem is crucial for improving the environment of mining areas. Remote sensing allows the dynamic monitoring of vegetation, animals, and landscapes in mining areas and can therefore facilitate the acquisition of change information, thus providing basic data support for ecological assessment.Due to the differences in physiographic conditions in mining areas, the biological species in different zones within the mine areas are also different. At present, research on the biodiversity of mining areas mainly focuses on vegetation, animals, and microorganisms. Mining areas contain a large variety of plant species  of numerVegetation type and quantity, as well as planting area and density, can be monitored with the use of remote sensing data. The vegetation index, as a common monitoring tool, has received considerable attention. At present, there are more than 200 vegetation indices published in the scientific literature, based on comprehensive remote sensing data ,48. AddiCompared with the studies on remote sensing monitoring of vegetation in mining areas, there are few studies on remote sensing monitoring of animals. On the bare land of mining areas, satellite remote sensing and unmanned aerial vehicle technology can be used to monitor animals ,54; howeUnlike direct monitoring of animals and plants, commercial sensors cannot directly identify the physiological status of microorganisms. At present, research on the remote sensing monitoring of microorganisms involves two aspects: one is to infer the physiological status of microorganisms from other organisms, soil quality, and water quality, and the other is to establish the microbial distribution model ,58,59. IAlthough remote sensing monitoring of the species composition and the dynamic evolution of ecological communities is achievable in large mining areas or in areas with intensive mining exploration, a vast volume of data and documents is required in addition to the remote sensing data. In general, environmental monitoring in mining areas mainly focuses on vegetation monitoring, while the monitoring of animal and microbial communities in such areas needs to be strengthened.The landscape pattern of mining areas includes the types, quantities, spatial distribution, and configuration of ground features. For remote sensing data, the landscape patterns manifest as plaques of different land use types, and the randomness, uniformity, or aggregation of these plaques in space form the basis of the landscape pattern analysis of mining areas . CurrentStudying the landscape pattern of mining areas cannot fully meet the requirements of ecological restoration of such areas, and the specific features of the study area and the study objects need to be considered. To plan and design mining cities , a new lRemote sensing allows the rapid acquisition of ground information, facilitating the timely monitoring of changes in vegetation, soil, atmosphere, and other environmental indicators when the climatic conditions and the topographical status of the mining areas change. Hence, remote sensing has become an important guarantee for improving the efficiency of mining area monitoring.Affected by mining activities, the growth status of contaminated vegetation can provide characteristic information based on differences in spectrum and texture. The methods of acquiring information such as the vegetation health status and the restoration effect from remote sensing images have been studied deeply, and impeccable monitoring systems have been widely applied . Since tCurrently, the differences between different vegetation types in mining areas, reflecting vegetation anomaly, can be distinguished through the vegetation index and biomass information, such as chlorophyll data ,75,76. HConsidering that mining areas have a complex environment, it is necessary to study the dynamic changes of the impacted vegetation during growth. In recent years, some researchers have begun to consider the relationship between “geophysical variables” and the variation of vegetation physiological characteristics ,88,89. ASoil pollution in mining areas is mainly a result of heavy metals , radioactive materials , acidified substances, and salinized substances ,91, whicHeavy metals in soil are generally monitored via remote sensing by establishing an inversion model of the heavy metal content based on the soil spectral reflectivity data measured in the laboratory . When stIn addition to the above methods of obtaining the contents of heavy metals in soil, the geological index can reduce the spectral changes caused by topography through the band ratio and can highlight some metallic materials in soil . CurrentRainwater erosion and surface runoff in mining areas lead to pollutant diffusion and, consequently, to groundwater pollution. The risks and paths of pollutant diffusion caused by surface runoff can be monitored and simulated through image data ,109,110,2, O3, and other gases, while the remote sensing data results can accurately fit PM2.5, PM10, and dust concentrations.Similarly, particles in the atmosphere can cause floating pollutants to spread around. Especially in non-metallic mine areas, the contents of toxic particles in the atmosphere are often high, which can have even more serious impacts on the environment than water pollution. For example, when studying the spatial and temporal distribution of mercury atoms in the atmosphere of the mining areas based on LiDAR data, the space near the mining area should also be included in the research scope ,117. In Water fluidity, water permeability, and gas diffusivity impede environmental monitoring in mining areas. However, with the further development of respective technologies, these difficulties will be solved, resulting in a higher accuracy of monitoring data.By combining the related research progress of remote sensing monitoring of the ecological environment in mining areas, this paper reviewed the status quo of the current technology from the three aspects of ground feature type monitoring, ecological status monitoring, and environmental status monitoring. The identification of ground feature types in mining areas is the basis of remote sensing monitoring, and the accurate identification of mining area boundaries provides the basic data for monitoring landscape ecology and the environment. Among the different monitoring methods used for mining area boundaries, the fuzzy clustering processing of land use status data can rapidly, easily, and accurately extract mining area boundary information. In remote sensing monitoring of mining areas, research on the diversity of the ecological landscape is relatively sophisticated, while the monitoring of animals and microorganisms is still in its infancy; in particular, the relatively high costs largely limit the monitoring of microorganisms. Remote sensing monitoring in mining areas mainly focuses on impacted vegetation and soil; although the research results are abundant, relatively few studies have considered water and air pollution. When monitoring the biodiversity of mining areas, vegetation monitoring mainly involves the identification and comparison of different plant species, while research on impacted vegetation in mining areas mainly focuses on the internal comparison of vegetation species. Land use/cover changes in mining areas are closely related to the ecological landscape diversity. They are interrelated with each other, but relatively independent. Generally, studies on the remote sensing monitoring of the ecological environment in mining areas are mostly isolated studies on a certain aspect, and there are few relatively comprehensive studies.According to different global division criteria, there are numerous different types of mining areas, and the environmental impacts of mining are broad. The effectiveness of remote sensing technologies on monitoring in mining areas varies according to the differences in region, the mining method, and the mined commodity. For example, the soils of most mining areas contain iron, and as a result, the remote sensing monitoring technology on iron elements in mining areas is more mature than the technologies used for other mineral elements . Due to Our paper is, however, limited in several aspects. For example, we reviewed the remote sensing technology for monitoring the ecological environment in mining areas according to the monitoring objectives instead of the technology type. This was mainly done to emphasize the progress of this technique in various fields rather than to focus on the remote sensing technology itself.Due to the limitations of remote sensing data, biodiversity monitoring in mining areas via remote sensing is not yet fully possible. Even for an advanced vegetation monitoring technique, there are few studies on the remote sensing monitoring of internal energy flows. However, in the future, with the further development of remote sensing satellites, remote sensing monitoring in mining areas will become more convenient, affordable, and faster, with an improved resolution and accuracy. At the same time, the stereoscopic monitoring by different remote sensing satellites and the comprehensive monitoring of the mining area environment with multisource data will be possible.


Controlled drug delivery is a matter of interest to numerous scientists from various domains, as well as an essential issue for society as a whole. In the treatment of many diseases, it is crucial to control the dosing of a drug for a long time and thus maintain its optimal concentration in the tissue. Heart diseases are particularly important in this aspect. One such disease is an obstructive arterial disease affecting millions of people around the world. In recent years, stents and balloon catheters have reached a significant position in the treatment of this condition. Balloon catheters are also successfully used to manage tear ducts, paranasal sinuses, or salivary glands disorders. Modern technology is continually striving to improve the results of previous generations of stents and balloon catheters by refining their design, structure, and constituent materials. These advances result in the development of both successive models of drug-eluting stents (DES) and drug-eluting balloons (DEB). This paper presents milestones in the development of DES and DEB, which are a significant option in the treatment of coronary artery diseases. This report reviews the works related to achievements in construction designs and materials, as well as preparation technologies, of DES and DEB. Special attention was paid to the polymeric biodegradable materials used in the production of the above-mentioned devices. Information was also collected on the various methods of producing drug release coatings and their effectiveness in releasing the active substance. The constrained supply of medicines is one of the hottest topics dealt with in modern pharmacology. Monitoring the kinetics of drug release has many benefits for patients’ health. It provides an improvement in the effectiveness of the drug-based treatment and reduces the severity of side effects. The sustainable drug release systems allow the active substance to be delivered precisely to the affected place in the right dose.the mechanisms of releasing the active substances ;release kinetics;materials used as carriers and delivery routes;medicines that can be used for appropriate therapy.The concept of controlled drug delivery systems (CDDS) refers to ensuring “programmed” drug releases over time and delivering the drugs to a specific place in the body. Research in the field of CDDS is being conducted in terms of:Meeting all of the CDDS objectives  is a considerable challenge.For decades, cardiovascular diseases have been at the forefront of death statistics. One of the most commonly used treatments for coronary heart disease  is percuThere are many types of endovascular prostheses and many criteria for their classification. The most commonly used categorization is the division into classic metal stents  and drug-eluting stents (DES—drug-eluting stents or DCS—drug-coated stents) .The first bare-metal stents (BMS) were quickly supplemented with modern systems supplemented by drug-eluting coatings. Releasing pharmaceutical agents from the stent surface was promising progress in the realm of cardiovascular stents . HoweverIt is assumed that the drug release process will be slow and programmed for controlled delivery . Moreovepermanent polymeric coating materials;metallic stent platforms;optimal drug-releasing condition, andthe factors that have recently been identified as disadvantages, such as:○the degradation of the products of polymers and○the presence of metal ions due to the erosion and degradation of metals and their alloys utilized in some stents as a metal base .Despite the supreme advantages of DESs over BMSs, in-stent restenosis (ISR) and long-term safety remain ongoing concerns in the clinical application of DESs. The prospective success of DES for long-term clinical applications depends on the following areas:Determining the direct relationship between stent materials and possible adverse effects is very difficult and has still not been done. For clinical success, it is essential to design DES that overcomes the problems commonly present in in-stent transplantology, such as the inflammatory response, delayed endothelialisation, and subacute stent thrombosis (ST) , simultaDrug-eluting balloons (DEB) introduced in recent years can be such an alternative in some clinical situations . The motDespite the existence of many types of stents and balloon catheters on the market, there is still a need to look for new technologies and materials to ensure their better mechanical, physicochemical, and biomedical properties.The number of publications on DES is increasing every year, reflecting the intensification of research related to this domain.This work is a literature review of the latest developments in the field of drug-releasing stents and balloons. The text collects a wide range of information and the latest scientific achievements related to these devices. It describes, among others, the compositions of stents and balloons, the drug-release mechanism, and coating techniques. The paper refers to the most frequently used DES preparation procedures, such as coating, immersion, and spraying methods. Attention was paid to the low quality of the above-mentioned mechanical coating techniques, and studies showing new ways of stent loading improving the quality of DES were cited ,16.Since polymers are an essential component of DES and DEB and, at the same time, remain the most controversial part of the technology of these devices, this work collected the information on the most commonly used and currently studied polymers . It repoStent design parameters may be listed as follows: the dimension of the stent struts, the full expansion of the stent, the radial strength of the stent, the extent of the balloon injury during the stent deployment, the nature of the disease itself (the intensity of the obstruction of the artery), the ability to tolerate the compression exerted by the vessel wall, the minimum longitudinal contraction by the time of expanding, and the amount of flexibility of the stent, especially for curved vessels to suitably flex in them ,18,19.The stent material are required to be nonerodible, noncytotoxic, resorbable, flexible, radioopaque, biocompatible, compatible with the chemical nature of the drug, and ideally, to have sufficient radial strength.Titanium (Ti) and its alloys have been reported as potential materials for the stent backbone, with excellent biocompatibility and corrosion resistance as a result of a stable oxide layer on the surface. A new Ti-based alloy was proposed by Saleh et al.  as the sIn turn, the selection of the covering material for the stent surface must be made according to the following criteria. The surface coating must be appropriate for the best adhesion of drugs, be compatible with drug molecules, and be biocompatible .In general, materials to be implanted or injected in the human body need to be both chemically and mechanically stable in the biological environment for long-term use. Thus, deciding for a potential biomaterial, a dual approach must be undertaken : (1) stunew generations of drug-eluting stents,nonpolymeric stents,bioresorbable polymer-coated stents, andfully bioresorbable scaffolds .Monitoring of the drug release process in the physiological environment is a crucial aspect of an effective treatment technique. A time-programmed drug release can make a balance between the drug release to the artery lumen and the drug absorption by the surrounding artery tissue. The key is to choose the right system for delivering medicine. The rapid rate of drug release might exceed the tissue uptake. In contrast, a slow release rate could delay the tissue-healing process . ContempStents can be ideal drug delivery systems, because they allow local releasing of the active ingredient into the vascular damaged area. Besides, the drug released from the stent can have the capability to inhibit the complex cascade of events that lead to building a new tunica intima after stent implantation . The potPrime DESs consisted of three main parts: a permanent metallic platform, a durable polymeric coating, and an active pharmaceutical agent incorporated into the polymeric surface that was being eluted from the polymeric layer . AdditioSignificant developments in the field of vascular prostheses have resulted in the use of matrix polymer coatings to release medicinal substances. Unlike classical metal stents, polymer-coated stents (PCS) show high plasticity and facilitate the placement of the prosthesis at the implantation site. The polymeric coating is, therefore, a suitable matrix for the controlled immobilization and release of antiproliferative drugs. Polymer layers on the stent surface have the following roles: (1) inhibiting the drug from being washed off from the stent surface, (2) providing a suitable scaffold for drug loading, 3) providing an engineered control over the drug release, and (4) providing a satisfactory platform for biocompatibility  providin.Based on the findings, the requirements for PCS have been established as follows . Firstlydelayed endothelialization caused by the locally delivered drugs,inherent thrombogenicity of the stent as a foreign body to the immune system,hypersensitivity and inflammatory reactions due to the base framework and/or polymeric coatings,insufficient drug amount in addition to a lack of sustained drug release, andstent displacement .First-generation DES does not match today’s medical standards . SeriousSince it was recognized that nonbiodegradable polymers could initiate an inflammatory response contributing to in-stent restenosis (ISR), polymeric materials with increased biocompatibility and biodegradability were proposed for stent skeleton construction. These much safer stents with thinner struts are known as second-generation DES .Biodegradable polymers have also been proposed as a coating material in DES to avoid adverse pathological effects and better control of drug elution . BiodegrThe idea of a new generation of stents based on biodegradable scaffolds, which is still undergoing R&D, was a big step in stent technology. This solution can give temporary support to the artery and fully biodegrades after completing its functionality. Scaffolds, as stated in papers ,42,43, pbiocompatibility: before, during, and after degradation;adequate radial strength;the proper time of degradation: not too fast to increase inflammation and not too long to provoke adverse body reactions—usually 4–6 months;no inflammatory process initiative by degradation;compatibility with DES technology, eluting drugs at a determined rate without any effect on the radial strength;thin struts;easy deliverability;enhanced visualization under fluoroscopy;compatible with currently available equipment for deployment; andimproved dwell time before implementation.Bioresorbable cardiovascular scaffolds (BRS) are a promising alternative to permanent stents in cardiology . The terThe absence of a permanent core has the potential to overcome the shortcomings of the conventional BMS or metal-based DES . BiodegrResearchers indicate the following potential benefits of using biodegradable stents: (1) restoration of cyclic pulsatility and normal vasomotion, (2) preventing ST, (3) normalization of shear stress and cyclic strain, (4) preventing constrictive remodeling, (5) reducing the risk of very late polymer reactions, (6) reducing atherosclerosis, (7) avoidance of late-vessel wall inflammation, (8) unjailing of side branches, (9) preventing acute occlusion, (10) restoration of normal vessel curvature, (11) preventing severe recoil, (12) preventing extensive remodeling, (13) avoidance of stent malapposition, (14) avoidance of late-luminal enlargement, (15) avoiding neointimal hyperplasia, and (16) a formation of a cap over the lipid-rich plaque. There is also no shortage of opinions among scientists indicating potential risks associated with the use of biodegradable stents. These include (1) unsuitable release profile for a drug delivery system, (2) higher risk of acute strut fracture as a result of insufficient mechanical strength compared with metallic DES, (3) increased rates of early thrombosis, (4) specific (cold) storage conditions and (5) specific deployment techniques, (6) difficulty in delivery to the site of action because of thicker struts with more extensive crossing profiles, (7) inadequate degradation and resorption profiles, (8) and inflammatory degradation residues ,48,49,50Biodegradable stents are promising candidates for vast future clinical applications. However, degradation of the stent is still the most concerning issue due to vessel recoil problems and hypersensitivity .It is important to mention that, until recently, surgeons were more likely to choose metal-based stents  rather than polymer-based ones (BRS), since the metal platform has a higher mechanical strength. Moreover, by loading stents with heparin (Hep), it was also possible to gain control of thrombosis . It shouDespite the predominance of polymers as a stent material, there are still uncertainties related to their use that require analysis: (1) understanding the mechanical behavior during and after implantation at the site of the injury and during its degradation and (2) comparing the efficacy of polymer-based and metal-based stents .lower stiffness and strength of polymer materials that make stent struts be thicker in comparison to conventional metal-based stents;increase in diameters of struts may lead to complications within the stent, such as platelet adhesion, and vessel injury;at a stress level below the yield and tensile strength of the material under consideration, premature destruction of a polymer may happen; the result is that, long before the polymer is degraded, the device fails in the face of the liquid pressure and the exerted pressure from the vessel wall; andmechanical behavior of the polymer and other bioresorbable polymers, due to molecular weight, temperature, molecular orientation, the crystallinity of the polymer, and degradation characteristics, is nonlinear.Among the potential complications arising from the use of polymers as a base material, it should be taken into account:Thus, it is of high importance to be familiar with a polymer’s behaviors before applying the device in the human body. Analyzing the stent action under simulated body conditions could help researchers make the best choice of a stent material and its composition . AssessiDrug-releasing polymers have found many applications in medical devices and are the most useful materials for the treatment of coronary artery disease. Biodegradable polymers have been widely investigated for use in tissue engineering and drug delivery. Among the desired features of a polymer, carriers are stable, compatible with drugs, nonflammability, and have sterilization resistance. However, it should be noted that polymers remain the most controversial component of drug-eluting technology .l-lactic acid (PLLA)). It covered a wide range of studies involving the mechanical testing of PLLA materials and PLLA-based scaffolds and computational studies that have been opening a new perspective to the predictions of outcomes . Ta. Ta65]. A serious disadvantage of the first- and second-generation stents is that the nonbiodegradable polymers used for their coatings remain on the stent after complete release of the drug, which may cause local hypersensitivity, tissue inflammation, and delayed vessel healing. Such stents may cause thrombosis in the late stage of DES .Recently, third-generation stents covered with fully biodegradable polymers such as PLGA and PLA have appeared on the market. ,72. One The presented-above solutions increased the effectiveness and viability of stents, but the problem of the metal scaffold (BRS) remaining in the artery after biopolymer degradation stayed unresolved . A signiThe latest achievement in low-invasive CAD (Coronary Artery Disease) treatment is the creation of the fourth generation of DES, which has a biodegradable polymer core modified with an active substance.The biodegradable polymers most often used as construction materials for scaffolds and as surface coatings for stents are described below.The thermoplastic aliphatic poly(esters), including poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic acid) (PLGA), have been widely examined due to their favorable characteristics such as biodegradability, biocompatibility, and mechanical strength ,80,81. Tg, and molecular weight and environmental conditions such as temperature and pH . T. T194]. Polymeric materials are used to coat the balloon to hold the drug for controlled release. Polymers adhere to the balloon before inflation and attach to the vessel after inflation to decrease thrombosis . Any matSeveral therapeutic substances can be applied to the balloon catheter surfaces. The agents can be antiplatelet, anti-inflammatory, antihyperlipidemic, antiproliferative, and antithrombogenic. Examples of each type of drug and their mechanisms of action are described in The drug release must be maintained in place to achieve a therapeutic effect. Moreover, no local or systemic toxicity may occur, and the delivery mechanism should not stimulate restenosis ,200.Controlling the release of drugs into the wall of a weathered vessel, when infalting the balloon, is a vital issue in the DEB design process. The critical parameter of the safety and efficacy of the drug is that it should be released at a desirable rate and without a loss of effectiveness. However, it has to be noted that DEBs are unable to secure a long-term sustainable controlled release of the active substance.Currently, DEB developers are proposing to use various biocompatible excipients to cover balloons to transfer drugs to arterial vessels more efficiently. Understanding the complex interaction between the shell and the artery, between the shell and the balloon, and the variety of administration sites has led to the development of highly specialised DEB .The research of Chang et al.  was focuThe methods of placing the drug on the balloon surface can be varied. Thus, depending on the model of the balloon and the technology used, there can be found: (1) ballons with the drug applied in an unbound form, (2) balloons covered with a protective layer preventing the premature rinsing out of the drug, and (3) balloons in which the drug is combined with an excipient facilitating its distribution on the surface of the vessel . ExcipieThere is a variety of excipients used today, such as iopromide, urea, dimethyl sulfoxide (DMSO), shellac, polysorbate and sorbitol, butyryl trihexyl citrate (BTHC), and polyethylene glycol (PEG) ,208,209.Iopramide, urea, shellac, and butyryl-trihexyl citrate are some examples of commonly used excipients . Urea isPharmacokinetics and the functionality of the transport and release of drugs are strongly regulated by the way the additives are placed on the catheter surface. The coating methods include dipping, air spraying, ultrasonic spraying, micro-pipetting, and others . Each ofAuxiliary substances for the transfer and retention of antiproliferative drugs have been used, among others, in DEB systems modified with paclitaxel. It is known that excipient substances play a vital role in the design and functionality of DEB. Still, the methods of coating balloons with excipients and antiproliferative drugs remain poorly explored. The aim of the research conducted by Turner et al.  was to dScientists believe that improving balloon coatings can lead to better designs and improved outcomes. Recently, Chang G.H. et al.  examinedThere are different methodologies for loading the drug onto a balloon, like spraying, dipping, micro-pipetting, applying nanoparticles, and imprinting the medicine onto the rough surface of the balloon  221]..221].Many innovative coating techniques are known in the literature, many of which have also been patented. Innovative coating methods offer a better-controlled mechanism of drug release increasingly, compared to other models of balloons not long ago used for continuous drug release. The solutions proposed are microcapsule coating, hydrogel coating, polymer-free coating, immediate-release coating, bioadhesive coating, and multiple layer coating.The technique proposed here is used to produce a balloon catheter covered with a sticky matrix of microcapsules as a reservoir for the administration of drugs. The surface of the balloon is covered with a layer of microcapsules containing either a single drug or a specific combination of drugs. Drugs adhering to the surface of microcapsules are released into the vessel when the balloon is filled and stretched.A sheath with a longitudinal weakness is applied over the viscous matrix. When the balloon is stretched inside the vessel, the viscous adhesive cracks, releasing the drug from the microcapsules into the vessel walls ,223. TheAnother new solution presented below is the modification of balloon surfaces with hydrogels as a carrier layer for various types of medicines. This type of layer contains a large amount of water and is highly hydrophilic, which improves its bioadhesion. Stankus et al. proposed hydrogel-coated balloon catheters as reservoirs for CAD drugs . The coaIt has been reported that bioadhesive polymers remain at the site of the inflated balloon for fifteen days to one month and later degrade . As prevPacetti and Stankus introduced a new type of coating containing a biodurable polymer with a bioactive agent, which upon exposure to the physiological conditions, showed the burst release of the bioactive agent. The maximum elution of the agent was observed within 60s of insertion . StankusRowe invented another method for the application of a therapeutic agent with the help of a catheter driving it into the internal tissue of the vessel. The therapeutic agent is mixed with a controlled-release carrier that stays for a more extended period and is biodegradable. This balloon catheter is used along with a stent .Roorda invented a biocompatible carrier to deliver a therapeutic agent through a balloon catheter containing a bioadhesive material . The balChristiansen developed multiple layers of polymer coatings with inner and outer membranes. The inner membrane surrounds the balloon, and the outer balloon membrane surrounds the inner membrane. The outer membrane is more compliant and porous than the inner one, enabling it to release the therapeutic agents into circulation . The twoAnother multilayer bioadhesive coating has been developed with the same bioadhesive polymer, containing an additional third protective layer impregnated with endothelial cell stimulant between the first and second coatings . The coaThe types of drug-coated balloons with regulatory approval status and clinical trials are presented in Drug-eluting stents and drug-eluting balloons introduced in recent years for widespread use in CAD treatments inhibit the inflammatory process. They have antimigration and antiproliferative functions, as well as support tissue healing. Despite many clinical studies confirming the angiographic effectiveness of the new types of stents and balloons described here, there are still too-few long-term observations confirming the effectiveness of these treatment methods.There are conflicting DES safety data on the frequency of late-stent thrombosis compared to bare metal stents ,233,234.The future of DES is not clear-cut and will depend primarily on technological advances, new structure design solutions, and an improved drug formula. An ideal stent should be characterized by flexibility, strength, and the construction optimally suited to the appropriate drug release . One of DES currently produced allow the use of different drugs and control the local sustainable release of active substances. Some metal stents have a special structure that enables direct coating without using polymer surface modifiers. Stents coated with biocompatible substances imitating tissue and cell surfaces are also available.Much attention is paid to polymers as carriers of therapeutic agents. They are responsible for the mechanical maintenance of the drug, keeping the chemical stability of the drug, and regulating the drug-release profile. Until now, the properties of polymers did not meet all expected requirements of researchers. The durability of the coating, physical properties adapted to the vascular tissue, compliance with the nature of the drug, biocompatibility, and controlled and prolonged release of the drug are critical requirements for polymers used in stents. In practice, it is almost impossible for all the desired properties to be present in one polymer. The solution may be to use a polymer mixture.Research is underway on new technologies to use biodegradable polymer-coated stents. The application of biodegradable polymers allows the use of large doses of the drug and reasonable remote control of the released treatment, as well as the complete degradation of the drug complex in a given time.Recently, a polymer-free DES has been designed to make up for the increased risk of late-thrombosis and inflammation ascribed to polymers. The advanced polymer-free stent design uses porous surfaces and reservoirs to introduce significant amounts of anti-inflammatory and immunosuppressive drugs. Preclinical and clinical trials have reported the comparable performances of both polymer-free and polymer-coated stents . HoweverIn the past several years, the limitations of DES (late-thrombosis and inflammatory reactions) have induced research on other treatment alternatives for atherosclerosis. Thus, a nonstent technology in which the vessel wall receives the effective homogenous delivery of an antiproliferative drug from the surface of an inflated balloon was created. The treatment goal of enlarging the vessel lumen and local drug delivery was achieved without implanting a permanent object. Balloon catheters should have adequate flexibility, high mechanical strength, and be thinly walled. These physical features are enabled by the use of special core materials such as polyvinyl chloride, crosslinked polyethylene, polypropylene, polyamides, polyimides, polyesters like polyethylene terephthalate, polyethylene , and nylon ,195. AmoDespite all issues discussed, drug-eluting stents and drug-eluting balloons are a significant alternative to “classical” cardiac surgery in the treatment of coronary artery disease.