The emergence of the deadly novel Coronavirus Disease (COVID-19) has resuscitated global attention on the state of health governance and well-being of citizens. Worldwide, countries are in dire dilemma of safeguarding the health of their citizens and equally salvaging economy, arising from the social distancing and lockdown strategies, which affects negatively the economic activities. This paper examines the intricate balance between health and the economy in the wake of the Covid-19 pandemic and the policy options needed to assist countries to implement strategies to protect the health of their citizens and promote economic recovery in this unprecedented global crisis situation. There is need for a coordinated public-private sector partnership in the recovery plan of each country, taking into account their contextual and country specific health system and economy, but not discarding the universal application thereof. Global, regional, national geo-political and public health collaboration is needed to save the world from COVID-19 catastrophic consequences. On 31 December 2019, the Chinese government reported the novel Coronavirus (COVID-19) outbreak in Wuhan, China. When China announced citizens presenting with pneumonia symptoms, it was found that the causative agent was Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).5The Coronavirus 2, which resulted in the COVID-19 pandemic, although dangerous, and a public health concern, is equally an independent international standard world-wide country governance assessor. It has exposed the strength or lack of institutional governance in countries worldwide: some have been found weak, non-resilient and some completely dysfunctional. There is no sector of the economy immune to the pandemic. Governments are compelled, not just to act fast and forcefully to beat the coronavirus and its economic impact, but equally to act in a manner that would guarantee effective and well-resourced public health measures to curb infection and contagion. Also there is need to implement well-targeted policies tailored towards supporting health care systems and employees. Such measures will shield the incomes of vulnerable social teams and businesses throughout the period of the virus outbreak. Understandably, immediate disruptions that may result from self-imposed shutdowns and travel bans cannot be offset by government support. Supportive economic policies, however, will revive business confidence and aid the recovery of demand as virus outbreaks ease.Over the past decades, scholars and practitioners have analysed the impacts of epidemics and pandemics especially the socio-economic impacts and have provided insights into ways of handling pandemics.Every continent is affected by the COVID-19 pandemic. As of 27 April 2020, global confirmed cases of COVID-19 stood at 2, 858, 635, and 196, 295 deaths, across 213 countries in the world.14From a public health perspective, the upward trajectory of COVID-19 in African countries with weaker health systems is worrying. Although in principle, many African countries have expressed their readiness to manage COVID-19, which is commendable, however, practical and proactive measures regarding the availability of the rapid testing equipment, masks and protective wear for health workers is desirable. Furthermore, the respective countries’ Health Departments need to recruit more health workers to treat and manage patients in hospitals.Health is very critical to the prosperity of any society. The absence of health affects the overall well-being of an individual and limit movements. In the work place, poor health slows down individual performance levels, firm or organization productivity and ultimately income. This is what COVID-19 has caused and is causing. This disease has locked down economies and created wide-ranging socio-economic disruptions in different countries across the world. For instance, banks have lowered their repayment rates on housing loans; and there is temporary cancellation of value-added tax (VAT) receipts associated with small businesses and company taxies, amongst other `protecting and saving the economy’ measures. The unavoidable impact of all these measures is that government revenues have dwindled. Artisans and petty traders have been left without recourse whilst some small-scale businesses and even some big ones have collapsed, especially where there is total lockdown. Schools are closed resulting in months of lost education. The impact is felt across all sectors as the most effective mitigating strategies according to experts and WHO still remain hand washing, social distancing and lockdowns.10From a public health perspective, health epidemics of the Middle East Respiratory Syndrome (MERS outbreak in the Asian nation) of South Korea, the Ebola virus in West Africa, and the current novel COVID-19 have international health impacts and drastic socioeconomic disequilibrium of life in the society.Apart from the morbidity and mortality rates of COVID-19, the huge consequence of impaired productivity because of individual sickness, their social unit or their community are glaring.Given the already weak economy of some countries and the resultant draw back risks precipitated by the COVID-19 pandemic, the near-term challenges would warrant reinforcing some policy actions to contain the untold challenges of COVID-19. There is a need to strengthen health care systems, boost investor confidence and demand, and limit adverse economic effects. There is need for multilateral policy dialogue to curtail and foster agreements on acceptable containment. Policy measures are needed to cushion the economic impact of the coronavirus regarding inflation of essential commodities and services.As countries grapple with mitigation and containment, the socio-economic impact is affecting the containment measures which when relaxed, may have dire health consequences. This has called for a delicate balance between health and economic considerations. There are no easy choices. Each country will have to carefully navigate this dilemma within its context, but based on what the prevailing figures and available scientific evidence from experts reveals.Broadly, however, governments need two policy instruments to deal with the pandemic: A mitigating policy and a Post Covid-19 recovery and rejuvenation policy. The mitigation policy will be a Health policy-a Proactive Health Policy framework and Management approach. This will involve containment measures; protection of health providers  and incentives); Testing centres and kits; Isolation centres with relevant facilities etcetera), in addition to aggressive education and health literacy.Health education and literacy is important to mitigate the impact of COVID-19 on crises-affected populations. Some countries may have to create massive information and surveillance: people would need to provide a transparent image of travel history, health records, movement and different relevant data so as to assist identification of  infected persons. Therefore, governments and agencies can implement evidence-based approaches recommended by the World Health Organisation (WHO) for combating Covid-19. Hand washing hygiene could be an extremely effective public health intervention, amidst other preventative measures such as regular use of facial masks, safe coughing and social distancing.19The post Covid-19 recovery and rejuvenation policy or economic policy should include palliatives to encourage citizens to endure lockdowns and observe social distancing. To cushion adverse effects of the Coronavirus on vulnerable social teams, short-time operating schemes, could be implemented to boost the pliability of operating hours. Such schemes would protect jobs and pay, but they may not be pliable enough to defend temporary or migrant staff from lay-offs.20Governments can adapt several economic palliative measures to mitigate the impact of Covid-19 on households. These could include providing money transfers or state insurance, especially for staff placed on unpaid leave and guarantees for lower medical costs for all. Additionally, governments can reduce policy interest rates and possibly, provide economic stimulus packages to boost business confidence. Such measures would assist with the recovery of demand, once the spread of the virus eases and travel restrictions are lifted. However, such measures could be less effective in coping with the immediate supply-side disruptions that result from imposed shutdowns and travel restrictions.Discernably, this paper recommends coordinated public-private sector partnership recovery policy agenda with all stakeholders in health and business anchored on scientific evidence regarding balancing health and the economy that aligns to an informed systems approach and cost-sharing strategies in re-opening of businesses, without possible resurgence of the virus. This approach entails phased opening of the economy and educational institutions where the effect of the pandemic is wide spread. Importantly, there must be synergy between the Health policy and the Economic and Post COVID-19 recovery policy in order not to tip the delicate balance between health and economy. While some of these policy strategies and approaches may be contextual and country specific, they are nonetheless universal. The time for international geo-political and public health collaboration and solidarity is now and the world must save no resources in protecting regional, national and international populations and economies. Now is the time to spend to save!UGM conceived and wrote the first draftDTG read and edited the manuscript and is responsible and accountable of the study.All authors contributed to the writing of the manuscript, read and approved the final version of the manuscript.


The arrangement of myonuclei in skeletal muscle tissue has long been used as a biomarker for muscle health, but there is a dearth of in vivo exploration of potential effects of myonuclear organization on the function and regeneration of skeletal muscle because traditional nuclear stains are performed on postmortem tissue. Therefore, we sought a transgenic method to produce a selective and persistent myonuclear label in whole muscles of living mice.t test was used to compare wild type and transgenic mice.We bred together a mouse line with skeletal muscle fiber-selective expression of Cre recombinase and a second mouse line with a Cre-inducible fluorescently tagged histone protein to generate a mouse line that produces a myonuclear label suitable for vital imaging and histology of fixed tissue. We tested the effectiveness of this vital label in three conditions known to generate abnormal myonuclear positioning. First, we injured myofibers of young mice with cardiotoxin. Second, this nuclear label was bred into a murine model of Duchenne muscular dystrophy. Finally, we examined old mice from this line that have undergone the natural aging process. Welch’s The resulting mouse line transgenically produces a vital red fluorescent label of myonuclei, which facilitates their in vivo imaging in skeletal muscle tissue. Transgenic fluorescent labeling of myonuclei has no significant effect on skeletal muscle function, as determined by twitch and tetanic force recordings. In each muscle examined, including those under damaged, dystrophic, and aged conditions, the labeled myonuclei exhibit morphology consistent with established literature, and reveal a specialized arrangement of subsynaptic myonuclei at the neuromuscular junction.Taken together, our results demonstrate that this mouse line provides a versatile tool to selectively visualize myonuclei within both living and fixed preparations of healthy, injured, diseased, and aged muscles. A skeletal muscle is composed of a variety of cell types, such as myofibers, resident macrophages, muscle stem cells (satellite cells), and Schwann cells. A complete understanding of how skeletal muscle reacts to injury and disease requires the study of the interaction between these various cell types in the system as a whole. Skeletal myofibers, the focus of this study, are multinucleate syncytia. Myonuclei in a healthy, undamaged adult myofiber lie along the periphery of the myofiber, just under the sarcolemma . The relMyonuclei are difficult to study using traditional nuclear stains such as DAPI and Hoechst because they indiscriminately stain all nuclei in the tissue. It is difficult to identify in whole mounted muscle tissue which of these stained nuclei reside within the myofibers because skeletal muscle tissue contains the nuclei of a variety of cell types and many of these cells are pressed tightly against the sarcolemma. Furthermore, although Hoechst is sometimes used for live staining in vitro , 18, it All experimental procedures were approved by Texas A&M University Institutional Animal Care and Use Committee and conducted in accordance with the National Institutes of Health guidelines. Animals were sacrificed via intraperitoneal injection of Euthanasia-III Solution (Med-Pharmex).http://www.clst.riken.jp/arg/reporter_mice.html), knocked into the Rosa26 locus and driven by the Rosa26 promoter . Skeletal muscle fibers of mdx mice have a preponderance of central nuclei, so we sought to use the RG transgenic label to visualize central myonuclei in the mdx model. To this end, the HSA-Cre79, H2B/GPI, and mdx alleles were bred into the same mouse lineage, to create the RG/mdx line. Two mice from this line were sacrificed, and representative images of whole-mounted soleus (SOL) muscle tissue are shown in Fig. mdx line , neither of which produced an appreciable signal. It is unclear why the GFP signal is so weak under the control of this HSA-Cre79 transgene while other Cre transgenes produce excellent labeling of cell membranes [There are numerous questions regarding myonuclei that can be investigated using this vital label. For example, the consequences of central myonuclei on the function of muscle fibers are not clear . It is pmdx, aging) is the increased presence of DAPI-stained nuclei that lie outside of the muscle fibers. In the aged and mdx animals, these areas of immense extra-myofiber nuclei are accompanied by mCherry signal that is dispersed and granular, often surrounding DAPI-stained nuclei. Considering that chronic muscle damage and inflammation are common in aged and mdx mice, it is possible that the DAPI nuclei belong to immune cells that phagocytose myonuclei from the damaged area of the muscle tissue, thereby producing DAPI stain surrounded with mCherry signal. Furthermore, the fact that at 1 day post-injury of young, healthy muscle tissue no mCherry label was left or observed in a dispersed, granular form suggests that the myonuclei of the damaged fibers may have been phagocytosed in a faster and more efficient manner than in the aged and mdx muscles. The RG mice may be useful for the in vivo observation and comparison of myonuclear degradation and the clearing of damaged muscle tissue in young, healthy animals compared to old or myopathic animals.The characterization of the mCherry label in RG muscles has already yielded interesting observations. For example, the subsynaptic nuclei seem to preferentially align adjacent to, rather than directly underneath, the BTX-stained AChRs. An explanation for this specialized arrangement of subsynaptic myonuclei could be that protein synthesis machinery that surrounds the nucleus, such as endoplasmic reticulum, is aligned directly under the synaptic gutters, leaving the nucleus to be positioned slightly to the side. Also, a feature common in all models of abnormal skeletal muscle tissue presented here (intentional damage, The role and consequences of myonuclear disposition and dynamics on the development, function, and regeneration of myofibers is an understudied, yet potentially important field of skeletal muscle research. The ability to specifically investigate myonuclei is limited, however, by the lack of reliable vital labels for myonuclei. The mouse line described here, with a transgenically expressed myonuclear label, provides a superior tool to study myonuclei in healthy, damaged, diseased, and aged skeletal muscle fibers in living and fixed tissue.


For WC and HC, the meta-analyzed MD for random effects showed a significant decrease . The risk of bias was also evaluated considering a high risk and a low risk according to PRISMA criteria. In conclusion, the results of this meta-analysis highlight a positive trend of probiotics supplementation on the amelioration of anthropometric measures of overweight and obese patients with related metabolic diseases. However, further research is needed before recommending the use of probiotics as a therapeutic strategy for these patients. The focus of the future research should be to evaluate the efficacy of different probiotic strains, the quantities to be administered, and the duration of the intervention.The aim of this systematic review and meta-analysis is to assess the effectiveness of probiotics in inducing body weight loss in patients with overweight or obesity with related metabolic diseases. The research was carried out on PubMed and Scopus, focusing on studies reporting the effect on anthropometric measures , waist circumference (WC), and hip circumference (HC) after administration of various probiotic strains compared to placebo. Twenty randomized controlled trials, that included 1411 patients, were considered. The meta-analyzed mean differences (MD) for random effects showed no significant decrease in body weight after probiotic supplementation (−0.26 kg ,  Firmicutes with parallel decrease of Bacteroides) and consequently their capability of harvesting energy from food , L. acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. bulgaricus) significantly decreased (p < 0.001) the BMI during a four-month supplementation period, with respect to the placebo group , p = 0.01), WC , and HC , but not the body weight  of adults of both sexes affected by overweight and obesity with metabolic related diseases. Probiotics seem to be mostly effective in NASH and metabolic syndrome patients.The results of this meta-analysis show that probiotic supplementation significantly decreases the BMI (−0.73 kg/mL. Casei strain Shirota (LAB13), L. Gasseri, L. Rhamnosus, L. Plantarum) and Bifidobacterium  show the most promising effects against obesity. A recent review shows promising in vivo and vitro effects of the same strains [According to this meta-analysis, the Lactobacillus , producing health-promoting and antimicrobial substances, excluding pathogenic microbes, and regulating the host immune system [The definition of obesity was based on BMI and the intake of probiotics was followed by a significant decrease of this outcome. The decrease of WC and HC may also be linked to the decrease of BMI. The difference between the results obtained for BMI and body weight may be due to the lack of homogeneity among the studies included in this meta-analysis because some studies considered only BMI while other studies evaluated only body weight or both of them. Very important is the observed significant reduction of WC and HC because these parameters, particularly WC, are strictly related to cardiovascular risk . One of e system ,52. An ie system .Lactobacillus reuteri has shown that it can prevent the intestinal colonization of pathogenic microbes, by remodeling the commensal microbiota composition, by decreasing the production of pro-inflammatory cytokines, and by increasing the strength of the intestinal barrier [Lactobacullus paracasei has shown in an animal model that it can decrease the fat storage by increasing the levels of angiopoietin-like 4 protein (ANGPTL4) [Lactobacillus gasseri SBT2055 (LG2055) has shown that it can reduce lipid absorption and promote fecal fat excretion in humans [Probiotics can play a significant role against obesity through species- and strain-specific mechanisms  Lactobac barrier . LactobaANGPTL4) . LactobaProbiotics can influence effective on obese and diabetic patients, through positively influencing the lipid profile and insulin sensitivity—both mechanisms can have an ultimate positive effect on the body weight, BMI, WC, and HC . ProbiotIn addition, probiotics also increase the production of short-chain fatty acids that eventually influence the appetite and energy homeostasis . The enhThe administration of probiotics for the management of obesity may represent an attractive therapeutic strategy but, even though encouraging results emerged from experiments on rodents, the efficacy of probiotics in obese humans remains highly debatable .The major limitations of this meta-analysis are due to the heterogeneity of the included studies. In particular, the age of patients showed a wide difference in the different studies and the same was for the duration on the intervention. The age of the participants ranged from 18 up to 75 years. The treatment duration also widely varied among the included studies, starting from 3 weeks up to 24 weeks. Both of these aspects negatively influence the data analysis and limit the understanding of the anti-obesity potential of probiotics.Thus, in future research, it is essential to define several smaller age ranges while conducting clinical trials so that the effect of age becomes clearer. The treatment duration also widely varied between the studies, starting from 3 weeks up to 24 weeks. This wide range of duration contributes to limit the understanding of the anti-obesity potential of probiotics with respect to treatment duration.This meta-analysis has various limitations based on the available scientific research, which is characterized by contradictory evidence. Part of the controversy is due to a lack of precise cost-effectiveness data and the lack of data on the correct dosage and type of probiotic that has to be supplemented. In addition, data on the correlation between specific claims and specific probiotics in obesity management are missing.A second point of weakness of this meta-analysis is due to the absence of RCT in which the population sample is normalized for colonic content of bacteria. Conceivably, the obese patients have an increased Firmicutes/Bacteroidetes (F/B) ratio and might require different probiotic doses. In overweight/obese humans, in addition, the low fecal bacterial diversity is associated with more marked overall adiposity and dyslipidemia, impaired glucose homeostasis and higher low-grade inflammation .Moreover, what constitutes a healthy microbiota is far from being established. For example, determining what constitutes a healthy microbiota and the variability found across populations is another important question mark. Recent studies raise questions about the widespread use of probiotics to impart general wellness .There is huge variability of fermentable substrates that have bulk effects on bowel functions. day-by-day and within a day, since many studies have revealed only minor effects on overall microbiome composition and usually show only few species changing in population size .Last, but not least, there is also no validated method to evaluate microbiota, most of which escapes current techniques, and in order to advance microbiome research to a more standardized and routine medical diagnostic procedure, it is essential to establish uniform standard operating procedures throughout laboratories and to initiate regular proficiency testing .The “energy extraction” hypothesis should be interpreted with extreme caution. Daily energy output in feces is about 500 KJ and the microbiota produces SCFA, hence contributing to energy production rather than extraction. Note that rodents, especially the gnotobiotic models, are poor models of human microbiota behavior .The results of this meta-analysis highlight a positive trend of probiotics supplementation on anthropometric measures of overweight and obese patients with related metabolic diseases. However, further research is needed before recommending the use of probiotics as a therapeutic strategy for these patients. The focus of the future research should be to evaluate the efficacy of different probiotic strains, the quantities to be administered, and the duration of the intervention.


Nondestructive testing with sensor technology is one of the fastest growing and most promising wheat quality information analysis technologies. Nondestructive testing with sensor technology benefits from the latest achievement of many disciplines such as computer, optics, mathematics, chemistry, and chemometrics. It has the advantages of simplicity, speed, low cost, no pollution, and no contact. It is widely used in wheat quality analysis and testing research. This article summarizes nondestructive testing with sensor technology for wheat quality, including the mechanical model, hyperspectral technology, Raman spectroscopy, and near-infrared techniques for wheat mechanical properties, storage properties, and physical and chemical properties  in the past decade. Based on the current research progress, big data technology needs a lot of research in spectral data mining, modeling algorithm optimization, model robustness, etc. to provide more data support and method reference for the research and application of wheat quality. Wheat is one of the staple foods of humans, and wheat flour is the main processed product of wheat, which occupies a large proportion in people's diet structure , 2. It cNondestructive testing with sensor technology has the advantages of easy operation, high efficiency and stability, good repeatability, and no damage to samples. It is widely used in the measurement and analysis of wheat quality . NondestWheat is the main food for people to maintain life. It is of great practical significance to analyze the storage and nutritional characteristics of wheat and provide a scientific basis for people's reasonable diet . For wheThe mechanical properties of wheat refer to various external loads  under different environments. The force and deformation characteristics of wheat piles under complex load conditions are an important reference for the design of grain storage buildings and an important part of safe storage of wheat and ensuring wheat quality. As shown in The triaxial test of wheat is a relatively complete experimental method to determine the mechanical properties of wheat in the current mechanical research and engineering practice. The triaxial test device is mostly a strain-controlled triaxial instrument, which uses a resistance strain sensor to make a local strain gauge. The main parameters of wheat grain piles are elastic modulus, dilatancy angle, and internal friction angle. The elastic modulus of the grain pile reflects the relationship between stress and strain within the elastic range of the grain pile, and it is also an important mechanical characteristic of the grain pile . The intThe conventional triaxial test can be used to test the mechanical properties of the grain. The triaxial test can not only study the stress and strain performance but also be an important method for other mechanical performance testing. At the same time, it overcomes the shortcomings of the fixed failure surface in the direct shear test, and the test results are more in line with the regulations.The triaxial test can simulate the local stress environment of the wheat grains in the granary and the mechanical properties of the wheat during loading and unloading. In the process of wheat processing, storage, and transportation, the crushing of grains has always been a major problem. The crushing of grains not only causes a huge waste of grain but also brings a series of problems to its transportation, storage, and production. Hyperspectral sensing technology has the characteristics of map integration, which can detect the fine spectral characteristics of elements that are lacking in wide-band imaging remote sensing, which is essential for fine quality identification and parameter inversion. Near-infrared light is an electromagnetic wave with a wavelength between the visible light region and the mid-infrared region. The wavelength range is between 780 and 2526 nm. It is the first invisible light discovered by people. Near-infrared spectroscopy technology is to use the material information contained in the near-infrared spectral analysis, which has many applications in wheat quality. For example, in terms of variety identification, using near-infrared diffuse reflectance technology, with hard white wheat, hard red spring, hard red winter, soft red winter, and soft white wheat planted in 1987, 1988, 1989, and 1990 as the research objects, 100 samples of wheat grading were systematically studied every year, and the correct grading of each variety of wheat was obtained . MarcottWheat scab is one of the main diseases of wheat, which occurs widely in the world. Near-infrared spectroscopy can also be used to detect the damage degree of wheat scab, and the content of deoxynivalenol and ergosterol in wheat grain can be determined. The accuracy level obtained shows the application potential of near-infrared spectroscopy in the detection of wheat scab , 34. WheIn the daily diet, wheat flour is an indispensable and important component, and its quality is related to people's health. The protein in wheat affects the quality of wheat flour. Scholz selects 6 different wheat backgrounds, each with a certain amount of flour or grains, and uses near-infrared reflectance spectroscopy and near-infrared transmission spectroscopy to detect the difference in the quantity and size distribution of wheat polymer protein possibility . Baslar Hyperspectral imaging is a powerful technique that combines the advantages of near-infrared spectroscopy and imaging technology, providing information about the chemical properties of objects and their spatial distribution. Diseases and insect pests have always been an important aspect of harming wheat quality. Singh selected 300 healthy wheat grains and 300 wheat grains destroyed by insects for hyperspectral imaging. The hyperspectral image was collected from 1000 to 1600 nm wheat grains. 85–100% of healthy wheat and wheat with pests and diseases are correctly classified . In addiPenicillium and Aspergillus niger were scanned, and the shortwave near-infrared in the range of 700–1100 nm was selected. Using multivariate image analysis methods to reduce the dimensionality of hyperspectral data and using principal component analysis to select effective wavelengths, studies have shown that the 870 nm wavelength is mainly used in classification and feature extraction [For other wheat diseases, such as smut, 48 grains were randomly selected from wheat with smut and normal wheat, and the wheat grains were studied using hyperspectral imaging technology. Through the rough inspection of the wavelength image, a fluorescence wavelength (531 nm) is selected for image processing and classification analysis. The results show that only using this wavelength, the classification accuracy can be as high as 95% . In additraction .α-amylase activity based on near-infrared spectroscopy. This analysis technology provides classification of grains based on characteristics such as variety, geographic origin, and core hardness [Like near-infrared spectroscopy, hyperspectroscopy is also effective in detecting wheat protein content. On a single-grain basis, 79 sets of wheat flour are selected to determine the distribution of whole wheat protein content, and HSI is used to predict this distribution for complete prediction. The protein content of a single grain could be accurately predicted . Hypersphardness . In addihardness . HoweverRaman spectroscopy is a new type of rapid detection technology that can enhance the sensitive detection of the molecular information of the compound through the sensor, so as to clearly analyze its characteristic chemical structure. It has simple sample preprocessing, fast detection speed, high sensitivity, and rich spectral information. Raman spectroscopy has great application value in the field of wheat quality detection. In terms of nondestructive screening and classification, Raman spectroscopy can be used to quickly and nondestructively screen DON-contaminated wheat and barley flour . A near-Raman spectroscopy was used to detect wheat tissues, and the mature grains of 3 common wheat varieties and 1 durum wheat were manually dissected. Using Raman spectroscopy to collect vibration spectrum characteristics on the film combined with statistical analysis, the specific spectral characteristics of each peripheral tissue of wheat were identified successfully . HoweverNondestructive testing is a technology that uses radiation, infrared, electromagnetic, and other principles combined with instruments to detect defects, and chemical and physical parameters of wheat without damaging or affecting the performance of the tested object. The triaxial test can consider the initial conditions of the test, simulate the stress path including loading and unloading, and provide the grain stress-strain model. Big data analysis of the wheat triaxial test can provide technical support for wheat storage. Big data analysis of the wheat uniaxial test can understand the mechanical properties of wheat grains, thereby reducing the compression and impact of wheat grains and improving wheat quality. Near-infrared spectroscopy is also widely used in wheat quality. Near-infrared spectroscopy analysis technology can detect the hazard degree of wheat grain scab, and nondestructively measure the potential of wheat grain hardness, the distribution of the quantity, and size of wheat polymer protein. Hyperspectral technology combines the advantages of near-infrared spectroscopy and imaging technology, and is outstanding in the detection of wheat diseases and insect pests and protein content. Raman spectroscopy is also mainly used in these areas. Big data can reflect the application of spectroscopy technology in wheat quality detection and screening, and provide technical support for wheat quality research. Nondestructive testing technology can also be applied to other grains, fruits and vegetables, and hazardous factor testing in the future.


The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity. The gut microbiota is a complex community of microorganisms inhabiting the gastrointestinal tract that have established a close symbiotic relationship with their human host. It plays a crucial role in health maintenance, allowing the metabolism of indigestible dietary components and the synthesis of some vitamins, preventing pathogen colonization, and contributing to the maturation and education of the immune system . The humLactobacillus rhamnosus GG, L. reuteri DSM 17938, L. plantarum DSM 9843, and Bifidobacterium lactis Bb-12 [Characterizing the bacterial populations involved in the dysbiosis is therefore important, as this might be helpful to adopt alternative strategies for management of diseases. For example, the increase of potentially pathogenic species could be treated through targeted antimicrobial therapies while the disappearance of beneficial commensals could be addressed by the administration of specific probiotics such as The general purpose of this review is to discuss the relevance of the Firmicutes/Bacteroidetes ratio as marker of obesity. First, we will describe the evidence suggesting an association between the Firmicutes/Bacteroidetes ratio and the obesity, or rejecting this relationship. Next, we will expose the possible reasons for these contradictions, in particular differences in the methods of analysis of the microbiota, the control of the interfering factors , and the possible biases in the recruitment process of the subjects. Ultimately, we re-analyzed the 16S rRNA gene sequence data from nine published studies to allow direct comparisons among their Firmicutes/Bacteroidetes ratio. Thus, we will show that obesity is associated with multiple taxonomic signatures, consistent with the high heterogeneity of the gut microbiome observed in the healthy population.Obesity is a complex, multifactorial, disease due to various factors including the host genetic background, decreased physical activity, and excess food intake. In the last few decades, the gut microbiota has been proposed as an additional factor favoring fat storage, weight gain, and insulin resistance . Indeed,Subsequently, the research efforts were focused on the identification of bacterial taxa involved in the development of obesity. Alterations affecting the dominant phyla Firmicutes and Bacteroidetes were first described in obese animals and subjects who exhibited increased abundances of Firmicutes at the expense of Bacteroidetes . When thHowever, in opposition to these results, a number of studies did not observe any modifications of this parameter or even reported decreased Firmicutes/Bacteroidetes ratio in obese animals and humans ,30,31,32Regarding this point, the hypothesis of the metabolic endotoxemia proposes that the increased adiposity and development of systemic inflammation could be due to the chronic exposure to lipopolysaccharide (LPS), a pro-inflammatory molecule derived from Gram-negative bacteria, which would pass from the gut lumen into the bloodstream . This hyStaphylococcus spp. and Lactobacillus reuteri (both from the phylum Firmicutes) have been reported in obese people, and positively correlated with energy intake and plasma >C-reactive protein (CRP), respectively [Faecalibacterium prausnitzii (Firmicutes phylum) correlated negatively with the intensity of low-grade inflammation in obese subjects and patients with type 2 diabetes patients [A. muciniphila (Verrucomicrobia phylum), a mucin degrading bacterium contributing to the stabilization of the gut barrier function, the secretion of antibacterial peptides, and control of inflammation [On the other hand, the increased Firmicutes/Bacteroidetes ratio did not correlate with the production of SCFAs observed in obese individuals. Indeed, MacFarlane et al. reported that Bacteroidetes mainly produce acetate and propionate, whereas Firmicutes produce more butyrate . Butyratectively ,45. On tpatients ,47. Obesammation ,49.On the other hand, the heterogeneity of the results in humans, regarding the Firmicutes/Bacteroidetes ratio, could be due to the insufficient number of subjects included in most of the studies, making their statistical power insufficient to detect small variations. Trying to clarify this issue, several meta-analyses pooling the high-throughput sequencing amplicons obtained from different studies in obese patients have been performed ,51,52. WThe discrepant results previously reported may also be explained by differences in sample processing and data analysis including the method of DNA extraction, the selection of the amplified 16S rRNA region (choice of the primers), the sequencing method, and the bioinformatic analysis  ,53,54. IAnother important factor is the platform used for sequencing the 16S rRNA amplicons. Several platforms  are currently available, which use different sequencing chemistry and can also introduce internal biases, for example by influencing the detection and abundance of microorganisms with low or high genomic GC content . In addiTo determine how the sequencing platforms can affect the results of microbiota composition, chicken cecum microbiota was analyzed through three different sequencing platforms  using the same set of primers (8F and 338R) . The autTechnological aspects, therefore, can strongly impact the identification of bacterial taxa, overshadowing biological differences in the samples, especially when the sample size is small . This prp-cresol, phenol, NH3, etc.). Non-absorbed dietary iron also (including iron supplements) affects the microbiota, as well as dietary phenolic compounds that may act as prebiotics. The impact of dietary lipids is poorly known; animals fed diets with high fat (supra-physiologic) contents exhibit gut dysbiosis but it is unclear whether this also occurs in humans [Comparisons of the results between studies are generally complicated by the inadequate characterization of the studied populations and the fact that many lifestyle-associated factors, not considered in the studies, contribute towards shaping the gut microbiota composition. Therefore, the discrepant results observed between studies evaluating the Firmicutes/Bacteroidetes ratio in obese and lean subjects could be explained by the fact that these co-variables have not been adequately considered. n humans . Interesn humans . Food adn humans ,68. Finan humans . AccordiPhysical activity is another important confounding variable; it determines intestinal motility and the transit time of the chime through the different segments of the gastrointestinal tract, which, in turn, affects the composition of the microbiota . PhysicaWithin a determined range of BMI, the marker bacterial taxa associated with obesity and cardiometabolic disorders were exacerbated in unhealthy individuals . As prevThe pattern of the gut microbiota associated with obesity is not homogeneous throughout the world and differs according to the geographical location of the studies ,85,86,87Prevotella [To assess the relevance of the Firmicutes/Bacteroidetes ratio as a taxonomic signature of obesity, we used data from microbiota composition from nine published studies carried out in seven countries  and including 728 healthy subjects. High-throughput 16S rRNA gene sequence data from previous studies, corresponding to V3–V4 or V4 hypervariable regions and generated by the Illumina MiSeq Platform, were collected . To alloevotella , resultsevotella . AlthougIn summary, the relative abundance of the Firmicutes and Bacteroidetes phyla is highly variable between subjects from a same population. This is probably due to many lifestyle-associated factors including diet, physical activity, food additives and contaminants, antibiotic consumption, physical activity, among others that influence the composition of the microbiota in the gastrointestinal tract. This could explain the contradictory results observed when comparing the microbiota between normal-weight and obese subjects, making it difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status. Though the gut microbiota could contribute to the development of obesity, the evidence suggesting an association between obesity and alterations of the Firmicutes/Bacteroidetes ratio is not convincing. In future studies, it is therefore necessary to improve the characterization of the subjects and to clearly identify the co-variables, which may affect microbiota composition and interfere with the interpretation of the results. In addition, the concept of a unique taxonomic signature associated with obesity appears compromised. Rather than investigate taxonomical marker of the obesity per se, obesity-associated gut microbiome studies should focus to identify taxonomic markers for stratifying patients into subgroups. Introducing microbiome patient stratification would improve the management of the obesity by personalizing treatment decisions through direct manipulation of patient microbiomes.


Molecules is an open access place for the dissemination of theoretical and experimental studies related to the chemical approaches to materials-based problems. Taking advantages from knowledge in chemistry, biotechnology, chemical engineering, physics, and materials science, the Section aims to become an interdisciplinary environment where the different expertise act synergistically to focus the progress in the field of creating and manipulating new materials. The “Materials Chemistry” Section of The Materials Chemistry Section benefits from the cooperation of 107 Editorial Board Members, responsible for the rigorous peer-review process and the high standard quality of the published papers. Their precious work allowed the impressive growth of the section, accounting for 567 published papers (seventh place among the different Molecules Sections). Authors and readers can take advantage of 117 Special Issues focusing on a specific area of materials chemistry and benefit from the contribution of recognized external Guest-editor or in-house Editorial Board Members. For celebrating the 25th anniversary, a Special Issue within the Section have been launched, together with a collection of the exclusive papers of the Editorial Board Members of the Section.As all the fields of chemistry, materials chemistry is experiencing rapid growth by taking advantages from the developments in the synthetic and characterization procedures, as well as from the new technologies available at the micro- and nanoscale. I am honored and excited to be of service to the scientific community of this section, where a significant number of excellent contributions have been published within the last 2 years. The present editorial is aimed at summarizing some hot papers of the section, in order to provide readers with a vision of their relevance and contribution to the growth of materials science and technology. The selected papers cover studies related to both the synthesis and characterization of organic and inorganic materials, including biomaterials, nanomaterials, hybrid materials, core–shell materials, thin films, and self-assembling systems. Hydrogels, due to their fascinating physic and chemical properties, high hydrophilicity, swelling, micro-/nanosized pores, and softness partly mimicking the soft living tissues, are proposed for a plethora of applications in different fields of nano-/biomedicine, especially in tissue engineering. Cui et al. proposed gelatin methacryloyl hydrogels to construct multicellular cocultured 3D microtissues with high cell viability and improved functionality . They faIn biomedicine, hydrogels allowed the development of stimuli-responsive (or smart) delivery system able to fulfill specific therapeutic needs by controlling the release kinetics upon variation of an environmental stimulation. To this regard, Xu at al. reviewed the use of Schiff base linkages as click chemistry approach to synthesize smart hydrogels, i.e., at first, they classified and discussed the Schiff base chemistry highlighting the pH-responsive behavior and the possibility to modulate the biodegradation by selecting the appropriate nucleophilic agent to be reacted with the aldehyde functionalities, and then, epitomized the preparation and biomedical applications of hydrogels based on the Schiff reaction . The deformation mechanics of chemically responsive hydrogels, including either the computational models for assessing the hydrogel free swelling or the techniques used for quantifying the gel deformation was reviewed by Fennel and Huyghe , while VDifferent applications of hydrogels involved their use as a support for enzyme entrapment in the fabrication of solid biocatalysts. Amphiphilic-amino acid hydrogels composed of an aliphatic chain from myristic acid and l- and d-Phenylalanine were tested by Falcone et al.  for entrComposite systems in the form of nanomaterials have been also treated within the Materials Chemistry Section. Nanoparticle systems, indeed, by virtue of the high surface area to volume ratio and tuneable chemical and biological properties, offer a wide range of solutions for different therapeutic applications. Hong Wong et al. provided an exhaustive overview of polysaccharides and protein-based polymers investigated for nanosized drug delivery, discussing the development and clinical potential in their use as anticancer coadjuvants . Janus eNanoparticles are also attractive due to their antibacterial efficacy, as demonstrated in the study by Zhang et al., where upconversion composite nanoparticles NaYF4:Yb,Er containing Chlorin e6 with enhanced red light emission were designed for the efficient photodynamic treatment of periodontal disease  8]..8].Apart than biomedical field, other applications of composite nanoparticles are photovoltaics and space missions. The improved photovoltaic performance of nanocomposite materials was demonstrated by Vázquez-López et al. by the synthesis of hybrid systems of SnO nanoparticles and conductive poly doped with polystyrene sulfonate . On the The applications field of materials-based researches are almost limitless, as underlined by other interesting articles within our section.With the aim of recognizing the future ahead of innovations in flame-retardant epoxy composites, Movahedifar et al. reviewed the reports on flame-retardant epoxy composites and classified them as a function of their flame retardancy performance by the use of the universal Flame Retardancy Index .Bou Orm et al. proposed organic–inorganic hybrid nanotitania supports functionalized with a series of organophosphorus molecules holding different unsaturated groups,  for the efficient removal of polycyclic aromatic hydrocarbons pollutants through π-stacking complexation  12]..12].Agrawal et al. addressed the need for the utilization of renewable energy sources for sustainable and environmentally friendly development of heating, ventilation, and air conditioning systems. They used nanostructured carbons (including carbon nanofibers and nanotubes) and the electrically insulating but thermally conducting hexagonal boron nitride  and nitrogen (N) atoms instead of C atoms), to enhance the performance of organic phase change materials such as n-nonadecane and n-eicosane . The interest of materials scientists in environmental problems was also highlighted in a review paper by Wang et al., where authors discussed the recent advances in the field of stable electrochemical energy storage systems  . FinallyMolecules aims to disseminate knowledges and promote cooperation between academia and industry in developing, improving, and finally scaling up new fascinating materials.These hot papers clearly demonstrated the impact of materials chemistry in everyday life. By hosting the recent advance in the field, the Materials Chemistry Section of


Myocarditis is an inflammatory disorder of the heart mainly caused by viruses. To investigate viral myocarditis, the Coxsackievirus B3 (CVB3)-induced myocarditis model is the experimental model used since more than sixty years. In the pathogeneses of viral myocarditis, the subtle balance between pro-and anti-inflammatory immune responses is of great importance for disease manifestation. Parallel to the infection of the heart, experimental CVB3-induced myocarditis results in an infection of the pancreas, causing a severe burden for the challenged animals. In frame of animal welfare, application of analgesics is mandatory. So far, positive as well as negative effects of opioids on the immune system have been described. However, the impact of opioid application on the pathogenesis of experimental CVB3-induced myocarditis has not been investigated yet. Since examinations on disease pathways and new treatment options rely on established models to generate reproducible data, applicability of opioids in experimental CVB3-induced myocarditis needs to be carefully evaluated. For this purpose, we summarized published studies for 13 different opioids and discussed their potential impact on the CVB3-induced myocarditis model.Myocarditis is an inflammatory disorder of the heart predominantly caused by infectious agents. Since more than sixty years, the Coxsackievirus B3 (CVB3)-induced myocarditis mouse model is the experimental model used to investigate viral myocarditis. The pathogenesis of viral myocarditis is conceptually a multiphase process, initiated by the infection of cardiomyocytes, followed by activation of the immune system, and resulting in myocardial fibrosis and left ventricular dysfunction. In parallel to the direct infection of the heart, CVB3 replicates in lymphatic organs such as the pancreas. Due to infection of the pancreas, the model of experimental CVB3-induced myocarditis is estimated as a severe burden for the challenged animals. Application of analgesics in frame of the animal welfare act (European directive 2010/63/EU) is more and more becoming a matter of debate. For this purpose, we summarized published studies for 13 different opioids and discussed their potential impact on CVB3-induced myocarditis. In addition, with this summary we also want to provide guidance for researchers beyond the myocarditis field to estimate the impact of opioids on the immune system for their specific model. In the literature, both immunosuppressive as well as immune-activating effects of opioids have been described, but examinations in experimental CVB3-induced myocarditis have still not been reported so far. Based on the existing publications, administration of opioids in experimental CVB3-induced myocarditis might result in more severe disease progression, including higher mortality, or a less pronounced myocarditis model, failing to be used for the establishment of new treatment options. Taken together, the applicability of opioids in experimental CVB3-induced myocarditis and in inflammatory models in general needs to be carefully evaluated and further investigated. Myocarditis is an inflammatory heart disease, primarily caused by infectious agents leading to heart failure . The entFollowing viral entry via the coxsackie-adenovirus receptor, apoptosis of cardiomyocytes and other cardiac resident cells is initiated ,7. This Due to the induced pancreatitis and associated weight decrease , suggestRelated to opioids, both immunosuppressive as well as immune-activating effects have been described . The immIn brief, the impact of opioids on the immune response is not fully explored and there are no data available for the use of opioids in CVB3-induced myocarditis mice. Therefore, this article aims to summarize the existing knowledge about different opioids commonly used in experimental research and to further discuss their potential effects in the context of experimental CVB3-induced myocarditis.In the current article, the use and described immune-related effects of 13 different opioids in rodents is summarized in view of their potential use in experimental CVB3-induced myocarditis. In detail, 13 different opioids , their dose, route of administration, duration, rodent species, and their impact on the immune system are stated in Based on their chemical modification, substances are classified into natural opium alkaloids , semisynthetic opiates , and synthetic opiates . Due to the different structures, differences in receptor binding  and subsBesides the already known immunosuppressive effects of morphine, further insights into the complex impact of different opioids on immunity could be generated by our literature research. Effects of the administered substances ranged from immune suppression to immune activation, forcing a closer glance on existing publications. It is still a matter of debate, especially in preclinical research, how opioids influence disease progression in experimental models and the exact mode-of-action is still rarely known. Therefore, it is still challenging for researchers to conduct their studies in accordance to the guidelines of animal welfare, avoiding severe burdens for their animals on the one hand and providing robust data with established animal models on the other hand.One major concern of the analyzed studies is that the corresponding measurements have mostly been performed in healthy animals and not in disease models. It is undisputed that results under normal conditions are completely different compared to the respective disease model. Little information exists related to the effect of opioid administration in disease models . In totaApart from that, the published studies often did not apply uniform dosages or application routes, which hampers direct comparison of results and does not allow a prognosis for other models. Furthermore, Sacerdote et al. only investigated splenocyte proliferation, NK activity and IL-2 production to determine the immunosuppressive potential of the used opioids ,47,48,49With respect to the heart, the impact of opioids on contractility, aging, ischemic pre-conditioning, and cardiogenesis involving several receptors has been reviewed . In ischThe occurrence of opioid receptors in the heart and their cross-talk to the cardiac β-adrenergic receptors might explain the cardiac vascular side effects caused by chronic opioid abuse ,58,59,60As described in the introduction, the pathogenesis of CVB3-induced myocarditis, of which all the established experimental models are conducted in mice ,62, depeWith respect to cardiac function, none of the cited studies investigated the impact of opioids on cardiomyocytes, or fibroblasts. Indicative for the extent of LV contractility impairment and myocardial remodeling in viral myocarditis mice may be the generation of ROS, which leads to increased apoptosis of cardiomyocytes followed by reduced LV function . FurtherAdditionally, previous own studies investigated the impact of various cell populations in the context of CVB3-induced heart failure ,65, inclTaken together, current evidence based on our literature search indicates that opioids have a modulating effect on the immune system. This implies that upon opioid administration the rodent model as such might be altered and the effect of the evaluated treatment option, influenced. Furthermore, knowledge about their impact on myocardial parameters is still insufficient.Given the current state of the research, we assume that depending on the used substance, a more severe disease progression, including higher mortality and an overshooting inflammatory response, or a less pronounced myocarditis, which fails to provide robust data, are possible. Since animal studies have to be conducted in accordance with the animal welfare act, researchers are faced with a moral dilemma, revealing gaps in this field. Although there are publications on patients who reported heart failure symptoms after chronic opioid use, local animal welfare authorities require published evidence for the exclusion of analgesics in the experimental model of CVB3-induced myocarditis due to the severe burden. Investigations of disease pathways and new treatment options rely on established models to generate reproducible data, and even small changes on experimental protocols might result in less comparability of the examined effects. On the other hand, it is well known that the physiological and neuroendocrine effects of pain can impact research outcomes. This controversy between animal welfare and good scientific practice reveals a major challenge for the future, especially since animal-free alternative methods in viral myocarditis research are non-existent at the moment. Therefore, the applicability of opioids in experimental CVB3-induced myocarditis, and in inflammatory models in general, needs to be carefully evaluated and investigated further.Already some years ago, the discussion about the applicability of analgesics in CVB3-induced myocarditis started. Due to novel regulations in frame of the European Directive 2010/63/EU, the use of analgesics is required by the local animal welfare authorities and to receive the formal approval for experiments causing severe suffering like CVB3-induced myocarditis is impossible without application of analgesics. As described above, the experimental CVB3-induced myocarditis model was established 60 years ago via intraperitoneal application of CVB3 . Besides


The global requirement of patient rehabilitation has surged with time due to the growing number of accidents, injuries, age-related issues, and other aspects. Parallelly, the cost of treatment and patient care also increased in a manifold. Moreover, constant monitoring and support for the patients having physical disabilities have become an ongoing challenge to the medical system. Robotics-based neurorehabilitation has reduced the human error while assisting such patients, precisely interpreting the signals, and communicating to the patient. Gradual precise application and improvement of the technology with time yielded a novel direction for patient care and support. The interdisciplinary contribution of many advanced technical branches allowed us to develop robotics-based assistance with high precision for the upper limb and the lower limb impairments. The present review summarizes the generation and background of robotic implementation for patient support, progress, present status, and future requirements. The human being is considered as one of the most complex machines on the planet Earth. However, the synchronicity between multiple systems, their organized interactions, and the appropriate responses to the environmental stimulations are astonishing. Managing multiple complex responses simultaneously appreciates the level of multidimensional organization and excellent coordination among the systems. All these coordinations are managed and maintained by the web of the neural system that generates and transmits numerous signals and responses in split seconds; thus, it helps the system to function in a smooth and effective manner.However, there are certain times when an unwanted interruption occurs due to any musculoskeletal or neurological disease, injuries, amputations, and similar reasons. Such painful conditions hamper the daily and regular movements and functionality of the patients and hence stall the normal life. Depending on the severity of the conditions, the time, process, and steps of rehabilitation differs. Therefore, neurorehabilitation is attributed to the highly complex process or systematic medical effort to help in recovering, restoring, or minimizing the losses from a nervous injury with all possible normal functionality in a human being . CertainThe need for neurorehabilitation was extremely felt important after World War II when several injured soldiers who averted death and infection required rehabilitation for their spinal cord and head injuries. Since then, the process of neurorehabilitation has observed a gradual development and novel applications for better therapies and applicability. Many major conditions can cause various degrees of physical disability such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, neuropathies, apart from the severe spinal cord, head injuries, and stroke. Guillain–Barre syndrome is another major cause that leads to restricted physical movement and often requires extensive rehabilitation and related patient care. Often, a complex neurorehabilitation process requires a team of professionals or experts to work together for optimum patient outcomes. Such teams may include specialized doctors and nurses trained in a particular type of rehabilitation therapy, speech therapist, patient and family counselors, and other experts depending on the case and necessity. The cycle of the rehabilitation process is implemented as mentioned in In the first step, evaluation for the specific requirement is inspected, followed by the requirement of specific application development. Later, the developed application is assigned into trial practices, if found suitable and effective; after verification, the developed application or protocol is continued, else further improvement is done depending on the necessity.The primary cases are majorly due to stroke, head injury, and spinal cord injuries which are allotted neurorehabilitation therapy on a short-term or long-term program based on the degree of treatment required. Often, stroke survivor patients require rehabilitation therapies due to partial or complete paralysis and decline or loss of functionality of a specific side or limb of the patient . FunctioThis type of injury requires the extensive rehabilitation program as serious head injury may cause physical, cognitive, learning, and movement impairments and can sustain life long, and it may require crucial support from the family and community members. Thus, such impacts cause personality alteration of the patient and require proper and detailed counseling of the patient and the family members. Head injury conditions are associated with several other factors during the rehabilitation process such as emotional and biopsychosocial aspects. A variety of patient outcomes have been standardized and reported to understand the recovery of head injury. Sleep disturbances and countering such issues remained an important aspect of accelerated recovery for closed head injury patients. Modern instruments and devices such as actigraphy and polysomnography are extensively used to monitor the neurorehabilitation process and progress the patient outcomes , 6.Spinal cord injury can lead to a severe degree of disability that may include paraplegia, impaired voluntary and involuntary reflexes, impaired bowel movement, and others. Such kind of situation may arise from an accident or similar incident. The complexity of the problem depends on the degree and area of injury in the spinal cord such as, for instance, tetraplegic patients having severe cervical injury may have much complicated problems. The impairment in the motor function varies depending on the spinal cord region affected, such as patients having an injury in the C5–C7 may have functionality in the upper arm. For spinal cord injury associated rehabilitation processes, several modern efforts are becoming fruitful such as application of brain-machine interface to stimulate the spinal cord specifically for precise outcomes and functionality , the aidSeveral disease conditions such as multiple sclerosis, Parkinson's disease, peripheral neuropathies, and Alzheimer's disease often sought neurorehabilitation. Numerous studies have been conducted in these aspects. Messinis and colleagues recently conducted a randomized controlled trial on the impact of the computer-based cognitive neurorehabilitation for the secondary progressive multiple sclerosis (SPMS) patients . They haAll these present research studies on the neurorehabilitation of various complex health conditions suggest that there is an urgent requirement for an interdisciplinary approach  and autoThe success of computer-based condition evaluation and systematic training and therapies about neurorehabilitation is another vital reason for embracing automation in the neurorehabilitation process. In the 1960s, such efforts were already under consideration, and there was some initial success as well. Brain injuries were assessed successfully through the computerized Wisconsin Card Sorting Test that helped in avoiding human mistakes. Functional memory was evaluated for the subjects using the Rivermead Behavioral Memory Test (RBMT) that examined the daily functions of a subject in relation to their functional memory. The online version of the same test (OL-RBMT) was effectively implemented and automated to evaluate a large number of patients accurately.The progress of the initial automation success for patients' evaluations allowed the researcher to upgrade the automation and to establish the human-machine interactions and understand the physiological aspect of the neurorehabilitation process through a machine-based automated way devoiding the possible manual error for better treatment and recovery. Some specific important progress is mentioned in the following section.Quantitative electroencephalography (QEEG) is a complex mechanical procedure that includes a great number of tools and techniques. This system captures the high-speed sequences of cognitive processes that happen in a fraction of a second in a specific order. Thus, automation of such a process can aid in tracking the patient's response towards a particular normal of applied stimulation . Such a Evaluation of brain functions and cognitive abilities are being tracked through the eye tracking system, a noninvasive and effective procedure to monitor the patient's condition , 23. To However, furthermore, the improvement was required to increase the interaction between the patient and the doctor, caregiver, or therapist. Virtual reality (VR) played a pivotal role in this context and aided to improve the neurorehabilitation program altogether. The VR system has been effective for stepwise cognitive training of the patients, especially those having difficulties performing daily sequential activities due to stroke or similar health issues . SimilarBesides, specialized cognitive training and special sequence-based regular activity training modern sensor-based methodologies are being implemented to support the patients who require mild, moderate, or serious support for their survival and activities. Automation has played an essential role for the patients and the caregivers at various stages of neurorehabilitation and helped the patients to compensate for their deficiencies upto a certain extent. However, modern robotics and artificial intelligence-based methods can yield further. Novel developments such as the decision support system (DSS), based on AI , automatImplementation of robotics depends on the prior assumptions and detailed evaluation of a specific patient condition. It requires application establishment with precise planning based on the in-depth analysis of the patient condition data. Individual problems are analyzed based on the specific nature of the problem, influencing factors involved, prognosis, type and severity of the impairment, mechanical and systematic limitations, and social and environmental issues. To scale and detect the level of impairment, activity, and participation, an array of tests and clinical assessments are completed.Movement, balance, and cognition are evaluated using many scales including but not limited to the Beck Depression Inventory, Mini-Mental State Examination, Behavioral Inattention Test, clock drawing test, Fugl-Meyer assessment of motor recovery after stroke, Orpington Prognostic Scale, and Montreal Cognitive Assessment. All these evaluations are performed to understand the degree of impairment in the patient. Similar to impairment assessments, another array of scales are used to understand the activity range of the patient; for instance, the Barthel Index, Action Research Arm Test, Timed “Up and Go” Test, Chedoke-McMaster Stroke Assessment, and Rivermead Mobility Index are extensively used depending on the necessity. Depending on the patient's emotional involvement and willingness, participation is evaluated using another set of standard scales. All these exercises are directed towards reducing the patient's uncomfortable situation and render a comparatively active independent daily life. Thus, the goal remains disability reduction, improved activity, maximum social acceptance, and participation. Robotics are successfully implemented to enhance such goals and relieve the impairment of the patient or improve the activity as much as possible.Upper limbs are mostly affected by the stroke survivors. Hence, a careful and extensive rehabilitation approach is required for their recovery and daily activity. Experimentation with the elbow-shoulder manipulator and assessing the stroke-affected patients suggested that robotic device support improved the patients' motor functions concerning the arm movement considerably when compared to the patients who not availed such devices. A meta-analysis on the application of distal and proximal arm robotics suggested that robotic-assisted efforts improve the motor function recovery of the upper limb function significantly for poststroke patients. Another similar investigation also suggested that robot-assisted therapy for the paretic upper limb (RT-UL) in poststroke patients significantly increases their practice repetition and improves the patient recovery substantially . AnotherSoft robotics systems are simpler in design, successful in enhancing safety, efficacious, and portable. The major applications are in hand rehabilitations . AssessmCare of an injured patient often requires long-term therapeutic sessions and hospital stay. The expenditure also surges depending on the therapeutic needs and duration of the hospital stay. Home-based robotic devices may become beneficial for automated robotic therapeutic approaches and ease of the process with required accuracy and precision. A recent report suggests that a patient in a condition to take the advantage of home-based Computer-Assisted Arm Rehabilitation (hCAAR) may improve their upper limb movement with minimal supervision. Availability and functionality of such devices can boost the psychological confidence and the independence of the patients and may reduce the efforts of the caregivers at home .Long-term therapeutic sessions require occasional outcome measurement to understand the gradual improvement of a patient undergoing rehabilitation therapy. However, the evaluation of the outcomes becomes cumbersome as the direct feedback from the patient less. Such a problem further intensifies while applying a robot-assisted exercise trial (RAET). Therefore, a defined, standardized, and acceptable outcome measurement approach should be applied for a better understanding of the therapeutic benefits for the patients. A recent study by Sivan and colleagues suggested that applying different outcome measures recommended by the International Classification of Functioning, Disability and Health (ICF) was found beneficial and appropriate . SeveralCerebrovascular injuries affect the motor neuron function in patients. Such patients require extensive rehabilitation therapies that may include functional electrical stimulation (FES) devices, artificial exoskeletons, and supports with brain-machine interfaces (BMC). Depending on the injuries and the damages, a combination of these systems could be applied for the best plausible rehabilitation of the patients. A combined approach with hybrid upper limb exoskeleton and brain-machine interface displayed promising results with increased accuracy in a recent study . FurtherApart from the mechatronics of the exoskeleton devices used for neurorehabilitation, understanding and categorization of the control systems are essential to understand the qualitative benefits and in the improvement of the quality of life in the patients. A better control interface may have excellent sensors with the best possible sensitivity, may support a higher degree of freedom (DOF) for limb movement, should consider more number of contact points for better movements, and should have superiority in assistance, correction, and resistance .In continuation of the several examples of robotics-assisted improvement of upper limb functionality for better neurorehabilitation in patients, applications are also reported abundantly for the lower limb functionality and activity improvement through robotics. Such a robotic system follows different rehabilitation principles such as foot-plate-based gait trainers, overground gait trainers, treadmill gait trainers, and ankle rehabilitation systems (stationary or active foot orthoses) . In mostSerious spinal cord injury affects and reduces the functional capacity of a patient through compromised neuromotor functioning; hence, the patient may have problems in gastrointestinal, urinary, cardiorespiratory, osteomioarticular, and other functional restrictions. Advanced applications of robotic-assisted gait are successful in improving the reflexes, feeling and sensitivity, electromotor and neuromuscular activity, independence and flexibility in limb movements, and psychological confidence. Such applications of robotic gaits also helped in reducing spasticity and pain in many patients .Understanding the neurophysiological mechanism in detail has been possible due to the advancement of science and technology. Such knowledge will lead to a better understanding of the normal neuromuscular system , 43. IntThe advancement of robotics further inspired the global effort to develop an integrated system with the utmost precision and flexibility for patients with varying degrees of impairments. The growing number of cases of chronic disabilities and ever-growing cost of patient care allowed the global researchers to develop large scale multidimensional and multinational projects such as the “Cognitive Assistive Living Ambient System—COALAS” where 1.6 Euro have been funded . The proThe robotics-based applications are showing their extensive promises in the process of neurorehabilitation for the patients and helping them regain their confidence through calibrated training, practice, and increasing their emotional and mental confidence. The state-of-the-art technologies combining biomechatronics, information technology and communication, mechanical engineering, biomedical engineering, and sensor-based approaches have raised the hope in the patients and the caregivers. However, there are several hurdles to overcome in the near future. Improvement of precision and accuracy, flexibility in the mechanical movement of the prosthetics, and development of personalized solutions are some of the crucial technical challenges. Most importantly, the cost-effective manufacture of such products and robotics-based assistive instruments can cater to a wide range of patient populations who are in desperate need of such support.Robotics-based neurorehabilitation has proved its technical mettle and applicability in many serious aspects of patient care, surgery, and neurorehabilitation. However, the time has come where a global standard should be determined and a further complete system-based approach has to be taken through large international collaborations to cater to the requirement of a huge patient who is in need. Today, great many options are available for different types of injuries of the upper limbs and lower limbs that may arise due to serious health issues. However, overcoming several technical challenges and financial issues may aid the patient population abundantly.


Pyroptosis, necroptosis, and ferroptosis are well-characterized forms of regulated necrosis that have been associated with human diseases. During regulated necrosis, plasma membrane damage facilitates the movement of ions and molecules across the bilayer, which finally leads to cell lysis and release of intracellular content. Therefore, these types of cell death have an inflammatory phenotype. Each type of regulated necrosis is mediated by a defined machinery comprising protein and lipid molecules. Here, we discuss how the interaction and reshaping of these cellular components are essential and distinctive processes during pyroptosis, necroptosis, and ferroptosis. We point out that although the plasma membrane is the common target in regulated necrosis, different mechanisms of permeabilization have emerged depending on the cell death form. Pore formation by gasdermins (GSDMs) is a hallmark of pyroptosis, while mixed lineage kinase domain-like (MLKL) protein facilitates membrane permeabilization in necroptosis, and phospholipid peroxidation leads to membrane damage in ferroptosis. This diverse repertoire of mechanisms leading to membrane permeabilization contributes to define the specific inflammatory and immunological outcome of each type of regulated necrosis. Current efforts are focused on new therapies that target critical protein and lipid molecules on these pathways to fight human pathologies associated with inflammation. Regulated cell death (RCD) can be triggered under several physiological and pathological conditions; yet, it is fundamental to keep organism homeostasis. Apoptosis is the best-known form of RCD, but in recent years, a number of new genetically encoded machineries leading to cell death have emerged. Pyroptosis, necroptosis, and ferroptosis represent, so far, the best-characterized non-apoptotic forms of regulated cell death ,2. DysreIn general, the plasma membrane represents the main target for the execution of pyroptosis, necroptosis, and ferroptosis, with the increase in its permeability being a shared key step at the core of regulated necrosis ,2. DespiLipids and membranes have fundamental functions in regulated necrosis. Individual membrane lipids can act as receptors of the protein executors in pyroptosis and necroptosis or as modulators of the properties of the plasma membrane required for their activity ,16,17. TPyroptosis is a highly inflammatory type of regulated cell death that is associated with the formation of membrane pores by GSDMs and often involves activation by inflammatory caspases 1 or 11 within the inflammasome complex . BesidesSpecific membrane lipids are needed for GSDMD engagement at the plasma membrane. In particular, GSDMD-N has a high affinity for acidic phospholipids such as phosphatidylinositol phosphates (PIPs) and cardiolipin (CL), and it can also bind to phosphatidic acid (PA) and phosphatidylserine (PS) ,23. A siGiven the high sequence homology of the N-terminal domain of GSDMs, it is very likely that these proteins follow a similar mechanism for pore formation . The lip+ and Ca2+, interleukins, and other small cytosolic proteins, even before cell lysis . One. One1]. Lipids and membranes are essential pieces of the necroptotic machinery that reshape MLKL from the cytosolic inactive state to the membrane-bound active form. MLKL inserts into the plasma membrane in a multi-step process ,38. Upon2+ or Na+ endogenous channels .,52.14,52radicals ,56. The ds PUFAs .Specifically, the metabolism of PUFAs and the collapse of cellular redox homeostasis have been identified as key processes in ferroptosis ,58,59. PClassic enzymes of lipid metabolism have been linked to ferroptosis through their essential role in the modification of membrane phospholipids. Acyl-CoA synthetase long-chain family 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) facilitate ferroptosis by mediating the incorporation of Acyl-CoA-PUFAs into membrane phospholipids  9,60,61,6160,61.2+ [2+ upon membrane damage correlated with the activation of ESCRT-mediated membrane repair, which had a pro-survival role by counterbalancing the kinetics of cell death and modulated the inflammatory signature of ferroptosis. Despite these findings, there is still no evidence about the protein- or lipid-based nature of these pores. It is a matter of strong debate whether peroxidation of PUFAs at the plasma membrane would be sufficient to cause its permeabilization. It has been hypothesized that peroxidized phospholipids and their derivate lysophospholipids could be directly toxic to cells through the formation of small discontinuities in the plasma membrane involving membrane thinning and increase of membrane curvature [Ferroptosis intrinsically involves the alteration of the properties of membrane phospholipids. However, there is scarce information about the membrane changes that are induced in this form of cell death. In addition, the specific membrane target of lipid peroxidation during ferroptosis is a matter of debate. Both plasma and mitochondrial membranes have been identified as potential main sites of lipid peroxidation in ferroptotic cells. Mitochondrial fragmentation, cristae disassembly, and mitochondrial outer membrane permeabilization are some of the dramatic changes in mitochondria morphology observed during ferroptosis ,61. Rece2+ . In agreurvature  (Figure Our understanding of pyroptosis, necroptosis, and ferroptosis as forms of regulated necrosis has improved largely in the last years. They all culminate with dismantling of the plasma membrane and therefore have in common the ability to activate inflammation and adaptive immune responses. However, the molecular details how these forms of cell death are executed and the precise mechanisms leading to the increase in plasma membrane permeability are specific for each type of cell death. While membrane damage is mediated by protein effectors in pyroptosis and necroptosis, lipid peroxidation leads to membrane disruption in ferroptosis. These different molecular executors determine the type of injury that is infringed to the membrane and the downstream consequences of membrane damage. Non-selective and relatively large GSDMs pores in pyroptosis allow the release of intracellular molecules such as pro-inflammatory interleukins, which act as activators of the immune system . EvidencThe plasma membrane is the final target of regulated necrosis and at the same time the 2D scaffold where protein executors can assemble to perform their function. In this regard, membrane lipid composition and its biophysical properties might strongly determine specific protein–protein and protein–lipid interactions required for the activation of the death effectors. In pyroptosis and necroptosis, membrane binding of GSDMD and MLKL takes places through protein interaction with specific anionic phospholipids. Membrane interactions are essential for the reshaping of proteins and the exposure of new interaction sites, leading to the assembly of functional oligomers, which finally punch the membrane. A special case is ferroptosis, which is dictated by alterations of lipid metabolism driving to the accumulation of lipid peroxides in cellular membranes. In this case, the obvious modification of the properties of the plasma membrane seems to affect both its integrity and the function of protein components of the bilayer.Altogether, it is clear that protein–protein and protein–lipid interactions, as well as plasma membrane dynamics, play essential roles in the regulation and execution of pyroptosis, necroptosis, and ferroptosis. As these forms of RCD are implicated in diverse pathologies, efforts are focused on the understanding of the molecular events at the plasma membrane that are relevant for these types of cell death. Improving our understanding of these processes holds potential to assist the development of new therapies that target membranes and lipid metabolic processes to fight human pathologies linked to regulated necrosis.