To describe, through a literature review, the results and benefits of oral and topical probiotics for adult patients with atopic dermatitis.A systematic review of articles published over a 13-year period was conducted to answer the following questions: (1) what information is given in the scientific literature concerning the use of probiotics in adult patients with atopic dermatitis? (2) Was there an improvement in the clinical status of the patients? (3) Was there a change in the microbial profile in patients after using such approaches? (4) Among the probiotics used, which was the most used in adult AD patients? (5) What was the average time of these interventions? (6) What were the outcomes?Seven studies with different sample sizes, ranging from 16 to 109 patients, were included in this review. These studies were all clinical trials (7/7), and probiotics (7/7) was the model of intervention chosen. Probiotics showed a potential to relieve the symptoms of the study groups with a reduction of pruritus and SCORAD when compared to the placebo groups. However, their effectiveness varied according to the strain, period, and form of administration.Many studies have demonstrated that probiotics improve the symptoms of atopic dermatitis and even its prevention. However, there is still much controversy and divergence concerning the real benefits. Despite this, probiotics have demonstrated a fair ability in improving AD adult patients’ symptoms in terms of decreasing pruritus and severity related to SCORAD. Atopic dermatitis (AD)  is charaThe clinical approaches to individuals with AD are to avoid triggering factors, the use of topical calcineurin inhibitors and topical corticosteroids associated with moisturizers due to transepidermal fluid loss, to control itching with the use of antihistamines, and in refractory cases, immunosuppressants may be prescribed . These mSome AD patients have food allergies due to the permeability of the small intestine. These allergies are commonly related to cow's milk, eggs and peanuts . Such alStaphylococcus epidermidis is predominant and, together with Staphylococcus cohnii, it could provide protection for the development of atopic dermatitis [Staphylococcus aureus. This causes an increase in permeability of the skin barrier in individuals with active eczema, and an instability of the skin barrier, which lead to a chain reaction, and consequently an inflammatory process [To understand these allergies in AD patients, it is necessary to know the microbial profile of AD. In healthy individuals, rmatitis . However process , 9, thro process –12.Lactobacillus (phylum Firmicutes) and Bifidobacterium (phylum Actinobacteria) genera, while Clostridium (phylum Firmicutes) or Staphylococcus (phylum Firmicutes) are associated with atopic diseases. These latter two microorganisms are also more commonly found in children born by cesarean delivery [The intestinal microbiota in healthy and AD individuals are also different. The intestinal flora of healthy individuals contains species of the delivery , 14.Lactobacillus and Bifidobacterium, and yeasts of the species Saccharomyces boulardii [Due to these differences in intestinal microbiota, various studies have proposed the use of prebiotics, probiotics and/or synbiotics as therapies in the treatment of AD patients –18. Proboulardii . Most ofoulardii .Prebiotics are nutrients that promote the growth and/or activity of certain species of bacteria in the intestinal microbiota, and thus benefit the host . TherefoSynbiotics have both probiotic and prebiotic properties. This appropriate combination of both components makes them have a superior effect than probiotics or prebiotics alone , 22.These alternative treatment therapies have demonstrated effectivity in treating a variety of conditions, including diarrhea, AD, and other chronic inflammatory conditions. The therapeutic potential is due in part to the effects of modulating the immune response, in addition to the competitive inhibition of microbiota components in the intestine and increased function of the epithelial barrier, which may help provide protection against the appearance of AD –18. AlsoHowever, although several species have been considered effective in preventing or treating atopic dermatitis, the efficacy of probiotics in controlling AD is still uncertain . Due to The methodology chosen for this systematic review was based on PRISMA  . The folatopic dermatitis", "probiotics", "prebiotics", "synbiotics" were previously verified by the MEDLINE Mesh. The inclusion criteria selected original articles, which addressed the AD theme only for adults, and where the title and abstract agreed with the proposed theme; only publications in Portuguese and/or English were accepted; publications and/or online availability were taken from the period January 2007 to June 2020. The exclusion criteria were studies with animal models; theses; books; dissertations; patents and literature and/or systematic reviews.A flowchart Fig.  of the bThe population sample included patients aged 18 years or older with a diagnosis of AD who used probiotics. The Intervention was to evaluate the use of probiotics in adult patients with AD. The Control group consisted of systemically healthy adult patients without AD. The Outcomes reported were: (1) whether there was an improvement in SCORAD after treatment with probiotics in adult patients with AD; (2) if there was a change in the microbial profile after the use of probiotics in adult patients with AD; (3) the average time of interventions using probiotics.Two independent reviewers selected the studies by crosschecking the keywords (C.S.S and M.S.V). Titles and abstracts were independently evaluated by the two reviewers (C.S.S and M.S.V), and duplicate studies, patents and articles that used animal models were independently excluded. When there was any disagreement between reviewers, a third reviewer determined the inclusion or exclusion of the study (J.L.E.).The data of the included articles were summarized, and the methodology of the articles was analyzed using quality assessment Table , based oThe relevant findings of each selected study such as: first author, country and year of publication, database used, sample number, type of study, SCORAD, treatment used (probiotics) and route of administration were extracted from the original studies to build Table The present review and the established criteria were based on the study previously published by Hulshof et al. .Quality Assessment according to PRISMA was carried out, and articles at levels A and B were selected. Then any duplicate articles were excluded leaving 7 articles for the present review  with a divergent sample size ranging from 15 to 109 patients. The choice of intervention in all these studies was probiotics (7/7). Studies with the use of synbiotics and prebiotics were not identified within the criteria established. The usage of the probiotics ranged from 8 to 16 weeks, with a mean of 10.28 weeks (SD 3.15).All selected studies used the oral route of administration; however, the presentation of the probiotics varied. As shown in Table p < 0.05), and there were further improvements in 12 weeks (p < 0.01) [Most studies (6/7) used the SCORAD  index T to class < 0.01) .Bifidobacterium animalis subsp lactis (LKM512- B. lactis) [The study by Roessler et al. , who use lactis) . Matsumo lactis) . The oth lactis) , 34, 35  lactis) .. [Lactobacillus paracasei, Lactobacillus acidophilus and B. lactis, and found a significant increase in the concentration of L. paracasei and B. lactis during the period of probiotic administration. Matsumoto et al. [B. lactis was significantly higher in the probiotic group compared to the placebo individuals [The Materials and Methods of the studies included numerous analyses. Most were blood analysis to evaluate Immunoglobulin E (IgE) in the serum and determine the Interleukins . In addition, the collection and analysis of feces was also carried out to analyze any changes in the microbiota after the administration of probiotics. This latter analysis was performed in five studies (5/7) –33 among.  who inveo et al.  found thividuals . Both thividuals , 31.staphylococci in the stools of the group treated with the probiotic Lactobacillus salivarius LS01 (p < 0.05). This result suggests that this probiotic treatment may have an important role in the modulation of Thl/Th2 cytokine profiles and could be considered as an important adjuvant therapy in the treatment of adult AD [On the other hand, Drago et al.  carried adult AD .lactobacilli, while the number of bifidobacteria and bacteroidetes remained unchanged. Although the fecal concentrations of short-chain fatty acids were not affected, fecal pH was significantly reduced from 7.0 to 6.6 in the AD patients after probiotic consumption.In 2012, Roessler et al.  also anaLactobacillus paracasei K71 (LAB diet group) and placebo group in different locations , but did not mention any epidemiological data of these patients [Based on the subjects’ characteristics, the study by Roessler et al.  evaluatepatients . Kaur etpatients  evaluatepatients , Matsumopatients  and Fangpatients  did not patients , 30. OthSeveral studies have pointed to probiotic therapy as an alternative for the treatment of AD. This is because probiotics can modify the intestinal microbiota early in pregnancy and influence the development of adaptive immunity. In addition to these factors, they have immunomodulatory effects, which allow their use to be aimed at patients with AD who have low microbial diversity in the intestine during the first months of life –36.This review obtained few findings in the literature, since testing of probiotics is more common in children and infants than in adults , 37–39. Another systematic review carried out previously by Hulshof et al.  selectedOn the other hand, like the present study, most studies (12/14) selected by those authors used the SCORAD index to assess the severity of AD. In their results, 3 out of 5 studies that used synbiotic intervention reported a reduction in AD severity after the dietary intervention compared to the control diet. This result was like the treatments that used probiotics, where there was an improvement in AD severity in 3 out of 4 studies. Hulshof et al.  observedp < 0.0001) in adult AD patients with L. salivarius LS01 taken orally twice daily. The probiotic was in sachets in powder form to be dissolved in water or another liquid according to the patient's preference, for 16 weeks. In their results, the authors observed a reduction in staphylococci in feces after the treatment with probiotics [P = 0.081) in patients treated with a combination of probiotics . However, this supplementation as a probiotic drink significantly increased the total number of fecal lactobacilli in both groups and a high number of L. paracasei and B. lactis was found, demonstrating good colonization of these organisms in the intestinal microbiota [Most of the studies in this present review described effective and beneficial results with probiotic treatments –33, 41. obiotics . Howeverobiotics  after 8 crobiota . This dicrobiota .A relevant factor to be considered in AD patients is the balance in the intestinal microbial composition, as these individuals tend to dysbiosis, especially favoring pathogenic microorganisms. There is evidence that probiotic bacteria can mediate beneficial effects by modifying the intestinal microbiota and its metabolic activity. Therefore, a supplemented mixture of probiotics can affect the peripheral immunological parameters, and relieve skin symptoms in patients with AD , 45. HowL. paracasei K71 powder dissolved in 100 ml of water once a day in their diet. The authors described that, symptomatic changes were assessed primarily by skin severity scores and secondarily by itching and impaired quality of life (QL) scores, collected at baseline and during weeks 4, 8, and 12 after the start of the intervention. In contrast, Kaur et al. [Lactobacillus fermentum. In addition to biochemical blood tests, they performed skin biopsies (4 mm) from the patients' backs before and after the study. The authors reported an improvement in skin condition, a decrease in SCORAD, and a reduction in oxidative stress in the skin and blood according to the oxidative stress marker (OxS) in their patients [Four of the selected articles , 41, 47 r et al.  used a dpatients .B. lactis LKM512 [The study by Matsumoto et al.  was the s LKM512 .Streptococcus thermophilus, enriched with L. paracasei Lpc-37, L. acidophilus 74–2 and B. lactis DGCC 420 for 8 weeks for adult AD patients. However, they did not observe an improvement in SCORAD or in the condition of the patients, and only reported an increase in fecal lactobacilli and a reduction in fecal pH with the supplemented probiotics [Roessler et al. , as presobiotics .Lactobacillus plantarum CCFM8610. The result of the sequencing analysis of the samples detected 23 phyla, of which four represented more than 98%. These four were Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria, with a predominance of Bacteroidetes (84%) and Firmicutes (86%). After the 8-week intervention, the relative abundance of the four phyla showed no variation between groups. However, in terms of the genus, there were changes in the intestinal microbiota. Before the intervention, there was a predominance of Bacteroides and Blautia in all groups; after the intervention, Bacteroides spp., Prevotella spp., Lachnospiraceae and Ruminococcaceae were dominant. In addition to these changes observed in microbial diversity, the authors also found a reduction in the SCORAD index, an improvement in the quality of life of patients and an increase in the expression of IL-10 in patients with AD, after the administration of the probiotic. Also, this approach was effective in preventing worsening skin condition of atopic dermatitis patients [Fang et al.  analyzedpatients .Bifidobacterium and Lactobacillus. Lactic acid has immunomodulating effects, and its fermentation by such microbial genera produces short-chain fatty acids, such as acetate, butyrate, and propionate. These metabolites serve as an energy source for colonocytes and are putative candidates for leukocyte ligands [The studies that have used prebiotics in vivo and in vitro, have demonstrated an increase in the expressions of IL-10, IFN-γ, IgA and TGF-β , 49. Fur ligands .In addition to probiotics and prebiotics alone, synbiotics are combinations of prebiotics and probiotics, in which there is stimulation of the latter by the former , 52. AltIn general, probiotics have numerous advantages, as they can be targeted to treat health conditions, control gastrointestinal diseases as well as help lose weight. Despite these advantages, the FDA (Food and Drug Administration) has not yet provided guidelines or recommendations for the use of probiotics. However, for AD, a specific protective effect of probiotics in primary prevention has been observed over a long follow-up period, especially in children and during pregnancy .Even though various clinical trials have been carried out with the most diversified methodologies and different probiotic strains, their results are still conflicting, especially in terms of clinical improvement in adult patients with atopic dermatitis. In general, our analysis showed that probiotics demonstrate a fair ability to relieve symptoms of atopic dermatitis in adult patients reducing pruritus and decreasing SCORAD index.


Escherichia coli or Salmonella due to the important digestive disorders that they can cause in many consumers) is of major importance. Using efficient and environmentally friendly detection systems for identification of various pathogens that modify food matrices and turn them into food waste faster will also improve agri-food quality throughout the food chain. This paper reviews the use of metal nanoparticles used to obtain bio nanosensors for the purpose mentioned above. Metallic nanoparticles  and their oxides can be synthesized by several methods, such as chemical, physical, physico-chemical, and biological, each bringing advantages and disadvantages in their use for developing nanosensors. In the “green chemistry” approach, a particular importance is given to the metal nanoparticles obtained by phytosynthesis. This method can lead to the development of good quality nanoparticles, at the same time being able to use secondary metabolites from vegetal wastes, as such providing a circular economy character. Considering these aspects, the use of phytosynthesized nanoparticles in other biosensing applications is also presented as a glimpse of their potential, which should be further explored.Nowadays, special importance is given to quality control and food safety. Food quality currently creates significant problems for the industry and implicitly for consumers and society. The effects materialize in economic losses, alterations of the quality and organoleptic properties of the commercial products, and, last but not least, they constitute risk factors for the consumer’s health. In this context, the development of analytical systems for the rapid determination of the sanitary quality of food products by detecting possible pathogenic microorganisms (such as  The world’s growing population and limited natural resources are closely linked to agricultural activity, and therefore, to productivity growth, which must take into consideration food security. As a result of globalization, the industrial agricultural practices evolved, increasing food production, but at the same time, the potential risk of food contamination increased. According to the World Health Organization (WHO), billions of people in the world are at risk, and millions become sick after consuming contaminated food every year ; therefoSimilar definitions of food are given by the Cambridge dictionary  and the Oxford dictionary  ,5.In terms of food safety, preventing contamination is the first approach, but despite careful handling, food can be contaminated by pathogens. Therefore, food nanotechnologies are necessary for food safety and analysis. Among other fields, the food industry is about to be revolutionized by nanotechnology. It seems that “nanoeating” represents a whole set of scientific ideas that are already being implemented and applied in the industry . First, There are many terms correlated with nanotechnology, but two of the most used expressions are “nanomaterial” and “nanoparticle”. While sometimes both expressions are used interchangeably, the American Society for Testing and Materials (ASTM)  states tOver time, for the detection and identification of food contaminants, various analytical procedures were developed ,11, usinThe present review aims to be a critical discussion regarding the use of metallic and metal oxide nanoparticles for sensing food pathogens. It contains general information regarding the different methods used for the synthesis of metallic nanoparticles , the types of bio-nanosensors for food applications, application of metallic nanoparticles for sensing food pathogens, safety and regulatory issue, conclusions, and future perspectives. The review also contains a chapter presenting the application of phytosynthesized nanoparticles as biosensors, as an example of the potential application of this particular type of NPs, which could become a viable “greener” alternative for food pathogens sensing.4, AgNO3, H2PtCl6, PdCl2, Zn(CH3COO)2, CdSO4, CuSO4, or Fe(NO3)3 [One of the main limitations regarding the use of NPs in a sensing application is related to the lack of a synthesis method that can, at the same time, lead to controlled size and morphology NPs, homogeneous in nature and with a narrow size distribution, with little or no toxicity, without using any potentially toxic compounds or hazardous techniques . From thFe(NO3)3 . (1)physical methods based on obtaining particles by physical exposure ;(2)chemical techniques in which the process of particle synthesis is initiated by chemical action;(3)combined methods of obtaining particles ;(4)biological methods based on bioreduction using plant extracts and bioreduction using microorganisms.The synthesis of metallic nanoparticles can be achieved by several methods:2 nanoparticles. There is a known method in which it is possible to obtain the highest degree of dispersion when using colloidal mills, whose principle is based on creating sufficiently large centrifugal forces in a narrow space between a rotating rotor and a stationary stator, leading to mechanical breaking of larger particles found in suspensions or emulsions . The simAnother method utilized for the synthesis of nanoparticles is the plasma method. In this case, plasma is produced by the radio frequency (RF) heating coil. The most used plasma processes are microwave and plasma-spray synthesis . A thermAerosol-based processes are mainly used for the application of coatings. Chemical precursors sprayed on a surface in a heated medium form nanoparticles after being subjected to pyrolysis . The metLaser ablation is a method for fabricating various types of nanoparticles. With laser ablation, using a high-power laser beam with an optical focusing system and a target feeding system, nanoparticles can be obtained . The chaMetallic nanoparticles can also be prepared by gas-phase synthesis. The gas-phase condensation process is the most used method of producing metal or metal oxide nanoparticles. The main parts of the condensing system are a vacuum chamber connected to a heating element, the material to be vaporized, a cooling chamber connected to a dust collection system, and a pumping system. The material in the vacuum chamber is brought to a temperature and pressure to establish a flow of matter, which collides with the gas present in the cooling chamber, forming spherical nanoparticles. Depending on the application, the coolant may be reactive or inert . Inert gThe technique is based on the electric charge of two electrodes composed of the metal to be vaporized. By exploiting the phenomenon of the electric arc, it is possible to vaporize small amounts of metal sufficient to form nanoparticles. Often, spark ionization is classified as an arc discharge, even though the two methods are slightly different; in the arc method, the discharge is continuous, while in spark ionization, it is momentary ,21. The 3O4, Au, and Fe3O4/Au NPs [In the case of sonochemical reduction, the chemical effect of ultrasound occurs due to acoustic cavitation, consisting of the formation, growth, and implosion of bubbles in the liquid. The implosion collapse generates a local hot spot by adiabatic compression or by the formation of shock waves in the gas phase inside the collapsing bubble ,23,24. T4/Au NPs . Althoug4/Au NPs .2 nanotube nanocomposite using this method [Gamma-ray radiation is a physical method used for metallic nanoparticles synthesis . Thi Kims method . Differes method .Microwave irradiation is another method for the one-pot synthesis of metallic nanoparticles in solutions. Morphologies and sizes of metallic nanoparticles could be controlled by changing the experimental parameters, such as the concentration of metallic salt, the type of solvent and surfactant, and the reaction temperature. Although the method has several advantages , it also has some major drawbacks, such as the relative high costs of the equipment and difficulties in the scale-up or reaction monitoring .2 NPs [Masaharu Tsuji et al. obtained Ag, Au, Pt, and AuPd nanoparticles using this method . The sam2 NPs ,41.Chemical methods represent the most common approach for the synthesis of nanoparticles. This involves a chemical reduction in the metal precursor using organic or inorganic agents. Various reducing agents, such as Tollens’s reagent, N, N-dimethylformamide (DMF), sodium citrate, ascorbate, and polyethylene glycol (PEG), are used to reduce metallic ions in different solutions. It is important to use stabilizers for dispersed nanoparticles during the synthesis and to protect nanoparticles that may be absorbed or trapped on surfaces, thus avoiding agglomeration . PolymerThe preparation of nanoparticles in biphasic aqueous organic systems is based on the spatial separation of the reactants (the precursor and the reducing agent) in two immiscible phases . The big4 with sodium citrate in aqueous solution at boiling point. Using this method, nanoparticles of different sizes, with diameters between 10 and 150 nm, can be obtained by only varying the ratio of the two reactants [The most popular synthesis method of spherical AuNPs is the Turkevich method, which involves reducing HAuCleactants . The majeactants . Another method for the synthesis of AuNPs of smaller dimensions is represented by the Brust–Schiffrin method. The very low-dimensions AuNPs (1–3 nm) are obtained in organic liquids in order to ensure the coating, which can control growth rates; using this method, anisotropic metal nanoparticles, such as rods, triangles, stars, or flower-like structures, are obtained . Although the methods described above provide high-quality nanoparticles, they use some chemical agents  known for potential biological risks, which only have limited stability of AuNPs in biological environments and still require high purification.A direct and simple process for the synthesis of AgNPs is represented by the Tollens method used for the synthesis of size-controlled Ag nanoparticles. This method includes a reduction in the Tollens reagent with an aldehyde . In the Another chemical method used to obtain metal nanoparticles is called hot injection, and it is a batch process in which chemical precursors are rapidly injected into a heated reactor containing a mixture of solvents and ligands . The met2O4 [2 [2SnSe3 [2NiSnS4 [Using this method, NPs of different size and morphology can be obtained, including metallic , bimetal2O4 , FeS2 [52O4 [2 , Cu2SnSe [2SnSe3 , or Cu2N[2NiSnS4 ).Uniform, size-controlled nanoparticles can be obtained using microemulsion techniques . The metSilver and gold nanoparticles were also synthesized by water-in-oil microemulsion method  by reducUsing the microemulsion method, different types of magnetic materials were also obtained, such as FeNi NPs  or magneThermal decomposition is another route  to synthesize monodispersed metallic nanoparticles, which are stable and of small particle sizes; no stabilizer is used for thermal decomposition . The metFor example, Unni et al.  obtained3O4, ZnO, SnO2, PbO, or TiO2 [3/H2O, respectively, the sodium acetate concentration.The polyol method is an important synthesis route, as it provides a high degree of control over both the size and geometry of the metallic nanoparticles. There are many papers that have reported the synthesis of oxide sub-micrometer particles: Mn or TiO2 ,68. The  or TiO2  obtainedThe sol-gel process represents a useful method for the synthesis of many nanomaterials, especially metal oxide NPs. This method of obtaining the metallic nanoparticles is fast, simple, and inexpensive. The sol-gel method presents numerous other advantages, such as homogeneity of the nanoparticles, the high purity of the end product, and the low processing temperature; the disadvantages of the method include the relatively high costs of the organo-metallic precursors, use of some toxic compounds, and the necessity for a post-synthesis calcination step. By this process, metal oxide nanoparticles, such as titanium dioxide, tin oxide, tungsten oxide, or zinc oxide, can be obtained ,71.2, ZnO, NiO, CoFe2O4, etc., can be obtained [Chemical vapor deposition involves a chemical reaction and one or more volatile precursors. The method allows the synthesis of high-purity and homogeneous NPs but is strongly dependent on the substrate; high temperatures are necessary, and the by-products are represented by toxic gases . Using tobtained ,73,74.Electrochemical deposition represents a process in which the NPs are obtained at the interface metal containing electrolyte/electrically conductive metal substrate . Using tFor example, silver nanodendrite NPs were obtained by an electrochemical technique, using pure metallic silver as an electrode, glassy carbon rod as a counter electrode, and an electrolyte prepared using deionized water .Microwave-assisted chemical synthesis is another method for obtaining metallic nanoparticles, using the advantages of the previously presented microwave synthesis and chemical synthesis. It has been reported, for example, that Ag nanoparticles were obtained by this method, involving sodium carboxymethylcellulose as a reducing and stabilizing agent. The size of the resulting particles depends on the concentration of sodium carboxymethylcellulose and on the silver nitrate concentration. The nanoparticles produced are uniform and stable . The proIn recent years, plant extracts have been used for the synthesis of metal nanoparticles, thus offering numerous benefits, especially in biomedical, pharmaceutical, and food applications, the nanoparticles and the natural compounds potentiating each other’s beneficial effects. Herbal extracts are one of the most studied categories today and are considered one of the most promising sources of natural reducing agents. The compounds in the extracts act both as reducing agents as well as stabilizers for the developed metal nanoparticles ,79; as sThe research area regarding nanoparticles obtained by this green synthesis method should consider the identification of plant-derived materials most suitable for the synthesis of specific nanomaterials/nanoparticles, as well as the clarification of the biochemical and molecular mechanisms involved in the formation of specific nanoparticles. Green nanotechnology, resulting from the combination of nanotechnology with the principles and practices of green chemistry, constitutes an important element in the development of an environmentally sustainable society in the 21st century. Current processes in the area of eco-nanotechnology involve the use of natural sources, non-toxic solvents, and energy-efficient processes for nanomaterials development ,81,82. Phytosynthesis of metallic nanoparticles  has, as a first step, the obtention of the extract, which can be achieved by extraction methods with classic  or modern instruments, such as microwave-assisted extraction. The factors influencing the morphological characteristics of silver nanoparticles are numerous, including the plant characteristics, the plant parts used, the extraction method, the solvent used, salt concentration, and other synthesis conditions ,83,84,85Raphanus sativus L. waste extracts [Aconitum toxicum Reichenb. rhizomes alcoholic extracts [Melissa officinalis L. extracts [Our research group evaluated in vivo and in vitro the silver nanoparticles phytosynthesized using extracts , gold anextracts , metalliextracts , as wellextracts .Camellia sinensis (L.) Kuntze extract (green tea) has been used as a reducing and stabilizing agent for the biosynthesis of Ag nanoparticles in aqueous solutions and under ambient conditions [C. sinensis extract increased, the resulting nanoparticles were relatively larger, wider, and more spherical. The phenolic acid biomolecules  present in the C. sinensis extract are responsible for the formation and stabilization of silver nanoparticles. It has also been reported that metallic nanoparticles were obtained from plants, including: dill, sage, orange, and grapefruit wastes, burdock, southernwood, asparagus, tangerine, Urtica dioica leaves, and Vitis vinifera fruits’ extracts, weed herb Cirsium arvense, or leaves and rhizomes of Asplenium scolopendrium L. [nditions . It was drium L. ,94,95,96Prunus × yedoensis Matsum. extract.Naseer and coworkers  reportedThymus schimperi leaves extract. The authors proposed the application of the developed NPs for metal removal from contaminated water.Additionally, the phytosynthesis of 20 to 30 nm magnetic magnetite nanoparticles with diverse morphologies was demonstrated by Geneti et al.  using ThAlthough the method has many advantages and can provide a true “green” character to the synthesis, it also has several disadvantages, including the difficulties in controlling the size and morphologies of the NPs and the incompletely elucidated synthesis mechanisms.Fusarium oxysporum has been demonstrated [Bacillus licheniformis [Bacillus subtilis) with the method of microwave irradiation in water. They described the extracellular biosynthesis of Ag nanoparticles using Bacillus subtilis, but instead of increasing the reaction rate and reducing the aggregation of the nanoparticles, they used microwave radiation, which helps to evenly heat the nanoparticles.Many studies have been performed on the synthesis of Ag nanoparticles using organisms  ,102,103.nstrated ,104. Verniformis . In addiniformis  have disFusarium oxysporum, with no evidence of particle flocculation even one month after the reaction. The long-term stability of the solution given by the nanoparticles may be due to the stabilization of Ag nanoparticles by proteins. The morphology of the nanoparticles varies with the shape, being generally spherical, occasionally with triangular shapes being present [Aspergillus flavus. These nanoparticles are stable in water for more than 3 months without any significant aggregation due to the surface binder of the stabilized materials secreted by fungi [Aspergillus fumigatus was investigated in 2006 by Bhainsa and D’souza [Ag nanoparticles (5–50 nm) can be synthesized extracellularly using  present . Stable by fungi . Extrace D’souza . The traAlthough the method is simple and leads to biocompatible materials, it has several drawbacks, including the difficulties in controlling the size and morphologies of the NPs, the long periods of time necessary for bioreduction, as well as the possible presence of endotoxins.Clostridium botulinum, C. perfringens, Bacillus subtilis, B. cereus), could be capable of producing heat-resistant toxins , or could grow under temperatures of less than 10 °C or in refrigerated conditions [Food contamination with pathogenic microorganisms or associated toxins can cause acute and chronic diseases and can lead to epidemics and death. Pathogenic bacteria exist in a variety of shapes and types and could be highly heat resistant  from different food matrices, generating a combined response pattern selective for every pathogen [The metallic nanoparticles can be used as sensing platforms for the target pathogen  band modification is a method based on changing the spectral characteristics induced by a variation in the local environment of gold nanoparticles, following biospecific interactions . This meE. coli O157:H7 presence in food determined serious issues for human health and financial losses for food producers. Meng Xu et al. [E. coli O157:H7 detection in pure culture and in food. They obtained bifunctional polymeric nanocomposites (PMNCs), which contained antibodies  and glucose oxidase (GOx). Firstly, magnetic beads (MBs) were linked to GOx by the streptavidin–biotin reaction, followed by obtention of a thin film of polydopamine (PDA) on MB-GOx by dopamine (DA) self-polymerization. The AuNPs were biochemically synthesized on the MBs-GOx@PDA PMNCs through the in situ reduction in chloroauric acid by the H2O2. As stated by the authors, the use of biocompatible PDA allowed the GOx to maintain its enzymatic activity to catalyze glucose to produce H2O2. ABs and GOx adsorption measurement led to ABs/GOxext/AuNPs/MBs-GOx@PDA PMNCs, which was used to separate the pathogenic agent from the food and to amplify the signal. Mixing the target bacteria capture method with labeling steps, these bifunctional PMNCs with AuNPs proved short detection time. Additionally, the transfer of the biological recognition to the signal took place because the numerous linking sites on the bacteria had abundant and active enzymes attached. Regarding the E. coli O157:H7 capture efficiency, the PMNCs with AuNPs captured about 89% bacteria cells between 102 and 105 CFU/mL. Considering about 10% bacteria losses, the PMNCs proved a good efficacy. The properties of this prepared biosensor demonstrated its efficacy in sensing food pathogens. The AuNPs were obtained using the method previously presented by Fu et al. [u et al.  developeu et al. . Fu et au et al.  developeListeria monocytogenes and Salmonella enterica, using the PCR method and thiol-labeled primers (PCR being applied to amplify the hly gene of L. monocytogenes and the hut gene of S. enterica). AuNPs (13 nm in diameter) were prepared by the citrate reduction in HAuCl4 and exhibited a characteristic surface plasmon band centered at 520 nm. Mixing the products with thiol label (as PCR results) and AuNPs, the sulphur–gold linkage resulted. These are more tolerant of salt than primers linked to AuNPs, so colorimetric testing using naked eye or spectrophotometric measurements could be used for pathogenic bacteria detection in food.Zhongyu Fu et al.  outlinedListeria monocytogenes (L. monocytogenes) from lettuces. Having a large surface (0.5 μm × 2.0 μm), L. monocytogenes possess numerous antigen epitopes, which act as binding carriers for the AuNPs, leading to AuNPs-coated bacteria complexes. In their research study, various parameters were changed until optimized development conditions were established and also to separate and concentrate L. monocytogenes from lettuce samples. Regarding the sensitivity and reproducibility of the AuNPs-based DLS immunoassay, NPs with three different diameters were obtained and used . Small-sized AuNPs were synthesized using the Li et al. method [L. monocytogenes in lettuce probes reached 2.2 × 101 CFU/g. Their values were much lower than the maximum limit imposed in Canada (100 CFU/g). The procedure was applied to 17 common pathogenic bacteria, but the results clearly demonstrated that the best results were recorded for L. monocytogenes detection.Xiaolin Huang et al.  reported. method , and med. method  based onE. coli (XL1), a visual sensitivity of 1 × 104 bacteria/mL, but for other bacteria, the sensitivity may vary depending on the bacteria species.Miranda et al.  developeSalmonella typhimurium detection in artificially contaminated pork meat. Large-area AuNPs were immobilized on the glass substrate, and the aptamer was bound to the AuNPs by a dipping process. Firstly, AuNPs with controlled size were synthesized as Neus G. Bastus et al. described [4 CFU/mL in pure culture and also in artificially contaminated pork meat probes, the S. typhimurium being identified using an aptamer as a linker between the AuNPs-conjugated system and bacteria.In recent years, NPs-based LSPR biosensors have been studied for their efficiency in the recognition of bacteria . In the escribed . SecondlBacillus cereus (B. cereus) in milk was developed by coupling asymmetric PCR  with propidium monoazide (PMA) and unmodified AuNPs [B. cereus in phosphate-buffered saline (PBS) and milk was 9.2 × 101 CFU/mL and 3.4 × 102 CFU/mL, respectively. According to the results, this method was appropriate to respect the maximum limit established by the Commission Regulation (EC) No 2073/2005 (500 CFU/mL) and is considered a good detection test for food-borne pathogens.A highly sensitive and rapid method for colorimetric detection of ed AuNPs . Under oShigella boydii (S. boydii) and Escherichia coli O157:H7 (E. coli O157:H7) in three types of food products using the colloidal gold immunochromatographic strip (ICS) was reported [6 CFU/mL for both food-borne pathogens, without any cross-reaction with other related bacteria. The LOD was enhanced to 4 CFU/mL when all three food products containing S. boydii and E. coli O157:H7 were pre-incubated.The simultaneous detections of reported . The patStaphylococcus aureus detection in milk. The resulting sensing method based on a composite antibody/AuNPs/carboxylated magnetic nanoparticle demonstrated high capture efficiencies for S. aureus in PBS of 96% and 78% in milk. Using the properties of both the magnetic nanoparticle and the AuNPs, such as magnetic separation and signal generation, the LOD of this colorimetric sensor in PBS for S. aureus reached 1.5 × 103 CFU and 1.5 × 105 CFU in milk.In 2013, Yun Ju Sung et al.  prepared+ ions caused by functionalization and oxidation phenomenon appearing on the surface of AgNPs. A very efficient immunosensor for S. aureus detection was fabricated by Abdolkarim Abbaspouret et al. [S. aureus primary aptamer fixed on magnetic beads (MB) that were coated with streptavidin for sample capture, an anti-S. aureus secondary aptamer conjugated with AgNPs [6 CFU/mL and a LOD of 1.0 CFU/mL.A variety of sensing devices are also based on silver NPs (AgNPs) ,145; thit et al. . For a sth AgNPs ,148 for Escherichia coli detection with surface-enhanced Raman scattering (SERS) was achieved by Naja et al. [Escherichia coli ATCC 13529 and Rhodococcus rhodochrous ATCC 17895  were used, and the results showed that, although the two bacteria were present, only E. coli was absorbed by the AgNPs. The proposed Raman scattering technique and also attaching an appropriate polyclonal antibody to the target bacteria on the nanoparticles surface assured specific and more selective bacteria detection results as compared to the traditional Raman spectroscopy. SERS with silver nano substrates were used for detection and identification of three food-borne pathogens  investigated by Wei et al. [Bacillus in food, mixing silver colloidal nanoparticles with the bacteria. The use of SERS techniques [2), Zinc oxide (ZnO), or silver oxide (Ag2O), due to their promising properties in food industries. CuNPs [2 nanocrystals, prepared as D. C. Pan et al. described [Salmonella in milk [Salmonella bacteria under an external magnetic field. The resulting magnetic nanoparticle/Salmonella was re-dispersed in PBS and exposed to antibody-immobilized TiO2NPs, exhibiting an increase in light absorption. Combining the immuno-magnetic separation with optical nanomaterials for Salmonella detection, a TiO2NPs-based immunoassay was obtained as a good alternative to the traditional methods based on PCR. The limit of detection for the targeted bacterium in milk was higher than 100 CFU/mL. When ZnO-NPs with special electronic configuration are used, the actions of the released Zn2+ ions are very important. The contact of ZnO-NPs with the pathogen surface determined the formation of electrostatic forces affecting the cell membrane [The a et al.  using poi et al. . For thei et al.  combinedi et al.  used SERchniques  for foodchniques , such ass. CuNPs  can be uescribed , were usmembrane . Some exThe development of successful bio-sensors for food pathogens sensing systems, as can be seen from the examples provided in the previous paragraphs, can be achieved by several different approaches.a.Listeria monocytogenes and Salmonella enterica  or for . cereus  and Bacis spores  in milk b.Physical deposition of NPs on different substrates represents another viable alternative. It can be achieved either by direct synthesis on the surface of different materials  [Shigella boydii and Escherichia coli O157:H7) conjugated gold nanoparticles  were obtained.The coating of metallic nanoparticles with specific antibodies was also presented in several studies. For example, Huang et al.  obtained strips)  or doubld.Salmonella antibodies were further immobilized [The functionalization of metallic nanoparticles was presented in several works. For example, Miranda et al.  obtainedobilized .All the approaches presented have their particular advantages and disadvantages. However, in order to pass from the laboratory scale to practical day-by-day application, the biosensor needs to be simple to use and to reveal the presence of the food contaminants. One such approach is represented by the incorporation of biopolymers to develop smart packaging materials . This woIn the large number of studies regarding the sensor application of metallic nanoparticles, the use of phytosynthesized NPs can be encountered as an alternative, “green chemistry” approach, usually for the detection of other types of contaminants (and not food pathogens). Although not directly focused on the subject of the present review paper, these applications can provide a glimpse on the future perspectives of pathogen detection technologies.2O2, a known oxidizing and bleaching agent used in several industries . As its discharge can cause significant damage to the aquatic ecosystems, there is a need for its rapid and reliable detection. Among other approaches, the use of phytosynthesized nanoparticles was evaluated for the biosensing of H2O2. Krishnaraj et al. [2, respectively. Similar approaches were used by different authors, applying phytosynthesized nanoparticles using algae or plant parts for hydrogen peroxide detection, heavy metals, organic substances , or even for the determination of a biomarker of prostate cancer [One such example is represented by the detection of Hj et al.  phytosyne cancer   are changed directly by the nanoparticles or nanoparticles-containing composites.All the examples presented in Particular attention is given to the use of metal nanoparticles that can be successfully implemented in numerous domains, such as food, biotechnology, medicine, cosmetology, etc. ,204. HowThe risks related to the use of nanoparticles can be avoided by testing changes in morphological properties, the degree of inhibition of cell population growth and development, changes in the biochemical activity of living organisms and cellular components. Yeasts, algae, and other microorganisms can be used as a study model in microbial biotechnology. For functional tests to measure the inhibition or stimulation degree of a compound, which is observed by the maximum effect of 50% (dose/response curve), it is suggested to use the terms of effective concentration (EC50%) or inhibition concentration (IC50%) by the compound. The most widely used indicators for assessing toxicity are lethal concentration 50 (LC50) and maximum permissible concentration (CMT). Thus, these tests provide the opportunity to perform comprehensive research of the nanoparticles’ effect on the body ,208.The above indicators determine the opportunity to study the characteristics, properties, and effects of nanoparticles designed to elucidate the degree of influence on living organisms, knowledge that can promote ideas for their efficient use.The global and European organizations  take preIn August 2021, the European Food Safety Authority published two guidelines in their updated versions—“Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health” and “Guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles” ,211. Add(a)Regulation (EC) No 1935/2004 refers to the materials and articles intended to encounter food .(b)Commission Regulation (EC) No 450/2009 acts on the active and intelligent materials and articles that will interact with food, defined as “materials and articles which monitor the condition of packaged food or the environment surrounding the food” .(c)Commission Regulation (EU) No 10/2011 refers to the plastic materials and articles intended that will interact with food and emphasizes that “substances in nanoform” could have various toxicological properties .Being best related to MNPs use in the food industry, the European legislation can be found in the following:Regulation (EC) No 178/2002 is a General Food Law Regulation and lays down the general principles and requirements of food law .As can be seen from the example provided in the present review paper, nanomaterials in general and metallic/metal oxides nanoparticles in particular can provide important instruments for the identification and even quantification of food pathogens. Considering the potential risks to consumer’s health, this subject should be one of continuous development in the search for safer edibles.In order to develop any type of application using nanomaterials, the synthesis methods should be carefully selected, considering all their particular advantages and disadvantages.The incorporation of nanoparticles in sensing techniques is usually performed by several methods. The simplest approach is the direct contact of the nanoparticle solution with the analyte; this colorimetric assay is based on the SPR peak displacement when the pathogen is present, providing a faster, easier-to-use, and equally reliable method  compared with other currently applied methods. Other approaches are represented by the deposition of NPs on substrates or polymeric materials, antibodies’ coatings, or surface functionalization of NPs and their deposition on test strips.Future works in this area should be focused on the development of ready-to-use devices, either in the form of test strips or as smart packaging materials .Considering the safety issues previously presented, the phytosynthesized nanoparticles, with their tremendous advantages  ,83, can


Sarcopenic obesity (SO), the co-occurrence of sarcopenia and obesity, is associated with functional loss, frailty, and incapacity in older adults. Recently, SO was associated with reduced cognitive performance in adults. However, no SO studies have been done with older adults with Alzheimer’s disease (AD).The objective of this study was to verify the occurrence of SO and associated factors in 43 older adults with AD.We applied the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). SO was verified by using dual-emission X-ray absorptiometry.We found five women with SO. Women had higher body fat and lower muscle mass compared with men. There was a significant relationship between body fat and cognitive performance only in men  adjusted by age and education. Men with obesity and aged >75 years had better cognitive performance compared with non-obese men aged <75 years (p=0.010) and women with obesity aged >75 years (p=0.033).Women with AD had higher body fat and lower muscle mass than men. SO occurs in older women with AD. Men with higher body fat showed better cognitive performance, independent of age and education. AD is a neurodegenerative disorder involving progressive decline of episodic memory and cognitive and functional capacities. Environmental and other factors are associated with increased risk for AD. Cerebrovascular diseases, diabetes, hypertension, obesity, and dyslipidemia are the most commonly reported health-related risk factors. Recently, sarcopenic obesity (SO) was associated with reduced cognitive performance in adults. SO is the co-occurrence of sarcopenia and obesity with low lean and very high-fat mass. Sarcopenia is associated with functional loss, frailty, incapacity, and cognitive impairment. Obesity is associated with inflammation and metabolic comorbidities. However, the association between obesity and cognitive impairment is controversial and influenced by the accuracy of adiposity measures. Depending on age, obesity can be either a risk or a protective factor for dementia. In adults aged <65 years, obesity increased the risk of dementia . In contrast, obesity was a protective factor for adults aged >65 years . In a population-based study, the SO rates were 12.6% in men and 33.5% in women aged >60 years old, and 27.5% in men and 48% in women aged >80 years. SO is more prevalent in women, people with diabetes and dyslipidemia, and/or among those who are sedentary. However, the prevalence of SO and risk factors among those with AD is unclear. Previous studies have evaluated obesity and sarcopenia independently from each other in older adults with AD, or the relationship between SO and cognitive decline in older adults without AD, but no studies of SO have been done with older adults with AD. Therefore, we examined the occurrence of SO and the relationship between body composition, age, and cognitive performance with SO in older adults with AD.Alzheimer’s disease (AD), the most prevalent dementia, affects 40–50 million people worldwideA total of 43 people  with medically diagnosed AD based on the National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer’s Disease-Related Disorders Association (NINCDS-ADRDA) criteria participated in this study as volunteers. Informed consent has been obtained from patients and/or caregivers. Two trained researchers accompanied by caregivers performed the anamnesis, cognitive evaluations, and anthropometric measurements at the participants’ homes. Subsequently, the participants went to a laboratory for the body composition evaluation using dual-emission X-ray absorptiometry (DEXA). The exclusion criteria were having incomplete data in the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), or the DEXA examination. A total of 18 men and 18 women had complete data sets and composed the final sample (n=36). The authors assert that all procedures contributing to this work comply with the relevant national and institutional committees’ ethical standards on human experimentation and with the Declaration of Helsinki 1975, as revised in 2008. The Ethics Committee approved the research protocol (# 3.363.878).We measured body weight in kilograms (0.01 kg) and height in centimeters (0.1 cm) by using an electronic scale and fixed stadiometer, applying standardized procedures. Total fat (%), lean mass (kg), and appendicular muscle mass (kg) were obtained from the dual-emission X-ray absorptiometry (DEXA) examinations. Obesity was classified based on body fat >28% for men and >39% for women (Cooper Institute for DEXA measurement).We used the MMSE with scores ranging from 0 to 30, with higher values representing better cognitive performance. AD stage was classified as mild, moderate, or severe using the CDR 1, CDR 2, or CDR 3, respectively.).It was assessed based on appendicular skeletal muscle mass index (ASMI) <7.2 for men and <5.7 for women. ASMI is the sum of the muscle mass of the four limbs divided by the square of the height in meters , version 25.0. The results were described as means and standard deviations or relative frequencies. Normality distribution was tested and confirmed by using the Shapiro-Wilk test. To compare age, education, and body composition between men and women, we used Student’s t-test. The relationship between body composition  and MMSE was assessed by using the Pearson correlation. The same relationships were tested, controlling by age and years of education . We compared the MMSE results among subgroups  using one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA), using age and years of education as covariates, with the Bonferroni post hoc tests. We clustered the older adults according to age (using the median as the cutoff point) and obesity/sarcopenic groups. We compared MMSE values using two-way ANOVA (sex × age — obesity/sarcopenic) with the Bonferroni post hoc tests, with years of education as covariates. The alpha value was set to be p<0.05.We analyzed the data using Men had significantly higher weight, ASMI, and residual value than women. Women had approximately 10% higher body fat and lower muscle mass and weight p<0.05; .. The use of DEXA allowed better measurements of muscle and fat tissues in our study. In our study, six women and one man had SO based on ASMI and body fat results from the DEXA examination. Similar to a previous study, our results indicate a higher prevalence of SO in women than in men. Besides, women had higher body fat and a lower appendicular muscle mass. In general, women are more susceptible to the development of osteoarticular diseases, the decline of strength and muscle mass, and obesity.We examined the occurrence and factors associated with SO in 36 older adults with AD. To the best of our knowledge, this is the first study to describe SO using DEXA measurements in older adults with AD. Few studies investigated the relationship between body composition and cognitive performance in patients with AD using indirect fat and/or muscle mass measures like circumferences, body mass index (BMI), or bioelectrical impedance. These techniques affect the diagnostic accuracy for sarcopenia and obesity. Obesity in middle-aged adults increases the risk for AD and may have a protective role on the aging brain in older adults. In our results, non-sarcopenic and older men showed the same cognitive performance as other age groups. In contrast, obese men aged >75 years had significantly higher MMSE values. Experimental studies are needed to explain the mechanisms involved in the age-dependent opposite effects of obesity on cognitive functions.Both the observed relationship between fat and MMSE in men and the higher MMSE values in obese older men reveal the importance of new studies exploring the age-related role of body fat and cognitive ability. From the few systematic reviews and experimental studies available in the literature, the results are still controversial and dependent on the measures used. Exercises, healthy eating, and weight management interventions are recommended to prevent and treat SO. However, a restrictive diet and pharmacological therapies can concomitantly decrease fat and muscle mass, increase sarcopenia, affect behavior , and/or intensify the AD degenerative process. Therefore, there is an essential gap for experimental clinical studies regarding therapies to treat SO.SO is associated with hospitalizations and lower survival timeThe limitations of our study include the lack of muscle function measures related to sarcopenia, the small sample size, and the possible survival bias since the study participants were volunteers from the community. However, the evaluations were performed using gold-standard measures and analytical recommendations, and the results provide relevant insights for future research and practice.In conclusion, women had higher body fat and lower muscle mass than men with AD; five women had SO. Men with higher body fat showed better cognitive performance, independent of age and education.


Spodoptera frugiperda, is an important pest in a variety of different crops. Graphene oxide (GO) is a promising candidate used in a biological context because of its versatility. In agriculture, GO could be potentially used as a pesticide additive to improve the efficacy of insecticides. In this study, the effects of GO on the development and reproduction of FAWs were determined based on life table analysis. The results showed that GO could prolong the duration of the egg stage and instar larval stages, but shorten lifespan of male and female adults, and this effect was enhanced with increasing GO concentrations. GO also reduced the number of eggs laid by female moths. In addition, the expression of genes related to reproduction have also been affected by GO. In conclusion, GO prolonged the developmental period of FAWs, decreased fecundity, and may decline the population size. The study provides a basis for the rational use of GO as a pesticide synergist for FAW control.Fall armyworm (FAW), Spodoptera frugiperda, which were reared on artificial diets containing nano-graphene oxide (GO), were determined based on age-stage, two-sex life table analysis. The results showed that GO had adverse effects on FAWs. Compared with the control, the duration of the egg stage and first, second, and sixth instar larval stages increased with increasing GO concentrations; however, the lifespan of male and female adults decreased with increasing GO concentrations. Weights of FAW pupae that were supplied with GO-amended diets increased by 0.17–15.20% compared to the control. Intrinsic growth, limited growth, and net reproductive rates of FAWs feeding on GO supplemented diets were significantly lower than the control, while mean generational periods  were significantly longer than the control. The expression of genes encoding vitellogenin (Vg) and vitellogenin receptor (VgR) expression was abnormal in female FAW adults feeding on GO-amended diets; the number of eggs laid decreased relative to the control, but Vg expression increased. In conclusion, GO prolonged the developmental period of FAWs, decreased fecundity, and led to a decline in the population size. The study provides a basis for the rational use of GO as a pesticide synergist for FAW control.The development and reproduction of the fall armyworm (FAW),  Nanomaterials (NMs) are small particles with a large surface area and high reactivity that have different degrees of toxicity toward the environment and living organisms ,2,3. NanAcheta domesticus, to GO in food caused an increase in oxidative stress, induced DNA damage, and caused an increase of apoptosis [GO has been used as a pesticide additive to improve the efficacy of insecticides. Sharma and co-workers reported that GO binds pesticides, reduces pesticidal drift and controls pests . Tong etpoptosis , which spoptosis . StudiesSpodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), commonly known as the fall armyworm (FAW), is an important pest in a variety of different crops [nt crops . It has nt crops . FAWs ornt crops ,21,22; int crops . At presnt crops . TherefoIn this study, FAWs were allowed to feed on different concentrations of GO, and the effects on FAW growth and population dynamics were analyzed using age-stage, two-sex life tables. In addition, expression of the vitellogenin and vitellogenin receptor genes to GO were determined. The responses of eggs, larvae, prepupae, pupae, male, female adults, and reproduction related genes to GO were evaluated, and the ecotoxicological effects of GO were used to provide a theoretical basis for safe, rational utilization of GO in FAW control.The original FAW colony was collected in 2019 from infested maize in Yuxi, Yunnan, China . Larvae were reared on artificial diets at 25 ± 1 °C under a 16:8 h light: dark photoperiod and 70 ± 5% relative humidity.Single-layer GO dispersion tablets  were purchased from Nanjing Xianfeng Nano Material Technology Co., Ltd. .Artificial diets were prepared as described for feed formula II  with minThe single-layer GO dispersion tablets used in this study were sent to Shanghai Huiming Testing Equipment LLC  for characterization and stability measurements. Transmission electron microscopy (TEM) was used to observe the ultrastructure of GO samples and the zeta potential was determined to evaluate the stability of GO dispersion.GO was added to artificial diets at 0, 0.5, 1, and 2 mg/g and an experimental population life table of FAWs was established to evaluate the effects of GO on the growth, development, and reproduction of FAWs. Newly hatched first instar larvae were transferred to 24-well plates with a soft brush and allowed to feed on diets containing 0 (control), 0.5, 1, and 2 mg/g GO to adulthood. After the females laid eggs, the eggs were dispensed to 24-well plates (2.0 × 2.5 cm wells), and each treatment contained 50 eggs and 3 replicates. The number of hatched larvae was recorded daily, and diets and plates were changed daily. The developmental period (time from egg to pupation), survival rate, time needed for transition from prepupae to pupae, and the weights of three-day-old pupae were recorded. After adult emergence, male and female sexes were distinguished by color and the presence or absence of markings on the forewing. Male and female FAWs were transferred in pairs to 1750 mL plastic boxes containing cotton balls soaked in 10% honey water. Gauze was placed inside the boxes to provide a platform for oviposition. The rearing box was placed in a growth chamber, and cotton balls were replaced every two days. After females laid eggs, the number of eggs and hatchability of each FAW pair was observed and recorded.xjS) represent the probability of individual FAWs surviving from newly hatched eggs to age x stage j, and a survival rate of 0 indicates that the FAWs failed to develop to the next age. Overlaps indicated the presence of generational overlaps in FAW populations. Survival rates were based on the daily survival of FAW populations, and age-specific survival rates (xl) represent the survival of FAWs from newly hatched eggs to age x, regardless of stage differentiation, where j represents the developmental stage andn0 is the number of eggs (newborns) at the beginning of the life table study.The duration of larval development, adult life span, and the fecundity of individual females were determined as described in xif) is the number of hatched eggs produced by female adults at age x and age-specific fecundity (xm) is the number of eggs per individual at age x.Age-stage-specific fertility (xl×x) is the product of xl and xm, and age-stage-specific life expectancy (xje) is the time that an individual of age x and stage y is expected to live.Age-specific maternity  is the contribution of individuals of age x and stage y to future populations:The formula for population parameters is as follows:r, intrinsic rate of increase:λ, finite rate of increase:R0, net reproductive rate:T, mean generation time:Based on ovarian development and prior grading of FAWs , female The total RNA of the sample was extracted with the Eastep SuperTotal RNA Extraction Kit ). RNA quality was evaluated by 1% agarose gel electrophoresis, and the concentration and purity of RNA were detected by spectrophotometry (Nano Photometer P-Class). RNA templates (2 μL) were removed, and cDNA was synthesized using the HiFiScript cDNA Synthesis Kit ). Total RNA and cDNA templates were stored at −80 and −20 °C, respectively.Vg gene released by NCBI  was used as an internal reference gene, determining the vitellogenin gene (SfVg) and vitellogenin receptor gene (SfVgR) in FAWs. FastStart Essential DNA Green Master Mix  was used for quantification of fluorescence. The total reaction volume of 20 μL contained the following reagents: cDNA template, 2 μL; ddH2O, 6 μL; and 1 μL each of the upstream and downstream primers (10 μmol/L). The RT-qPCR procedure consisted of the following steps: pre-denaturation at 95 °C for 10 min; denaturation at 95 °C for 30 s, annealing at 56 °C for 30 s, 40 cycles; 65 °C for 5 s, and then 95 °C for 5 s.RT-qPCR primers were designed by Primer Premier v. 6.0 using a conserved sequence of the  by NCBI . RPL27 e−ΔΔCt quantitative method. SPSS v. 24.0  was used to conduct one-way ANOVA for SfVg and SfVgR data, and Tukey’s HSD method was to determine significant differences. Relationships between stage-specific oviposition quantities, stage-specific hatching rates, and gene expression were determined by Pearson correlation analysis.The life parameters of the FAWs were calculated using the TWOSEX-MS Chart 2020 program . The meaThe sheet diameters of GO samples were between 50 and 200 nm , and theThe effects of different GO concentrations on the developmental stages of FAWs are shown . Comparep < 0.05,). After feeding different GO concentrations, the lifespan of male adults was also reduced and was the shortest at 1 mg/g (11.65 d). However, there was no significant difference in the lifespan of FAW male adults at different concentrations (p > 0.05). The total lifespan of FAWs was shortened by 2.12 d compared with the normal diet, and the average number of eggs laid was reduced by 1.81 times compared with the control . Similarly, FAW pupal weights decreased in response to GO treatments, and this was concentration-dependent; for example, pupal weight at 2 mg/g was 193.6 mg, which was significantly lower than the control at 228.29 mg (p < 0.05). Significant differences were also observed among treatments in the adult pre-oviposition period; for example, the pre-oviposition stage was longest (6.89 d) when the GO concentration was 1 mg/g  represents the amount of time an individual at age x age j was expected to live. The life expectancy curves of FAWs fed on the three concentrations of GO showed a slow decline .Age-specific life expectancy  and similar to the cycle-limited growth rate of the population life table parameter. The reproductive value of FAWs at different concentrations and stages increased with the maturation of instars and was highest in the adult stage, which indicated that the adult stage was the most important predictor of future populations. When GO concentrations were 0.5, 1, and 2 mg/g, the maximum age-stage reproductive values of female adults were 516.74, 506.03, and 372.36 offspring/adult, respectively; these values were lower than the control (598.42 offspring/adult) and peaked at 35 d, 36 d, and 35 d, respectively .−1 and 170.36 eggs, respectively. Intrinsic growth, weekly growth, and the net reproductive rates were highest in the control group and were 0.154, 1.16 d−1, and 329.37 eggs, respectively. In contrast, the average generational period was highest at 1 mg/g GO at 40.38 d, and this period was significantly higher than the other two GO concentrations and the control .Pearson-derived correlation coefficients derived for SfVg and SfVgR expression in FAW adult females consuming GO diets. Our findings further illustrate the toxic effects of GO on the reproduction and development of lepidopteran insects, which is consistent with a prior study that focused on the deleterious effects of GO on FAW larvae [Heliothis virescens and Trichoplusia ni, reduced pupal and adult weights, and decreased fecundity [−1 nanosilver significantly increased the body weight of silkworms and had no negative effects on survival but reduced cocooning rates in a dose-dependent manner [In this study, age-stage, two-sex life tables for FAWs at different GO concentrations were constructed based on laboratory experiments and the toxicological effects of GO on the growth, development, and reproduction of FAWs were determined. The results showed that GO inhibited FAW growth and development, decreased pupal weights, and reduced egg production. We also observed deviations in W larvae . HoweverW larvae ; this coW larvae . For exaecundity . In anott manner .Drosophila melanogaster and caused a significant reduction in lifespan and fertility [Spodoptera littoralis larvae and pupae [The growth rate of lepidopteran larvae depends on the efficient acquisition and utilization of essential nutrients in the diet. Food quality plays a central role in insect life history, physiology, and biochemistry and strongly influences trophic interactions . Our resertility . Furthernd pupae , possiblD. melanogaster diets and had no effect on growth [2 had no significant effects on the fecundity or mortality of Myzus persicae [2) at 100 μg/L, the permeability of the intestinal epithelial barrier was perturbed, thus causing inflammation and oxidative stress [Manduca sexta larvae after feeding [Nanomaterials vary considerably with respect to their effects on insects. For example, fullerene Cbo, carbon black, and single- or multi-wall nanotubes were added to n growth . Similarn growth . Furthern growth . Differepersicae . Howeverpersicae . In conte stress . It is a feeding . After iAcheta domesticus in a concentration-dependent manner [In this study, age-stage, two-sex life table analysis was used to evaluate the effect of GO on FAW populations. GO had significant effects on larval developmental time and FAW fecundity. High concentrations of GO significantly reduced the fecundity and reproductive parameters of FAWs. Other studies have also shown that diets containing high concentrations of carbon nanomaterials significantly reduce FAW fecundity and fertility . GO was t manner . SimilarSfVg and SfVgR showed abnormal expression levels compared to the untreated control, and there were time and concentration effects. On day three, the 2 mg/g GO treatment significantly increased SfVg expression, whereas SfVgR showed a significant decrease. Previous studies have shown that nanomaterials accumulate in living organisms, especially in reproductive systems where NMs may affect reproduction and development. When nano-TiO2 at 100 μg/L was applied to adult zebrafish, the NM particles were transferred to the gonads, resulting in abnormal levels of reproductive hormones, vitellogenin and other indicators [SfVg and SfVgR expression, which ultimately led to reproductive disorders and reduced fecundity. Panacek’s study showed that silver NPs were toxic to D. melanogaster, which resulted in the overexpression of stress proteins in vivo [2 was ingested by zebrafish, there was a decrease of the concentration of luteinizing hormones and a significant increase of the concentration of vitellogenin, which resulted in reproductive disorders [2 resulted in autophagy and necrosis of interstitial cells, spermatogenic cells, and spermatogonia, which led to reproductive toxicity [Vitellogenin and the vitellogenin receptor play important roles in the maturation of insect ovaries  and are dicators . In the  in vivo . Furtherisorders . GO nanoisorders . Kotil etoxicity .In recent years, numerous studies have been conducted to find out the potential toxicity of graphene family materials (GFMs) on different organisms when assessing the application prospects of GFMs. As stated by Jastrzebska and Olszyna, considering the increase in the use and production of GFMs and the consequent environmental emissions, their toxic effects are becoming an urgent issue . Some stSfVg and SfVgR expression, and other genes related to reproduction warrant further study to better understand GO toxicity in FAWs. In addition, whether GO has potential risk to the environment remains to be further studied.This study analyzed the effects of GO on FAW growth, development, and reproduction in the context of the age-stage life table of both sexes. This study provides a basis for further exploration of the ecotoxicological effects of GO on lepidopteran species and provides a theoretical basis for the rational utilization and deployment of GO for pest control. However, the underlying mechanism of GO toxicity for FAWs remains unknown and further research is warranted. Furthermore, this study focused solely on Vg) and vitellogenin receptor (VgR) expression was abnormal in female FAW adults feeding on GO-amended diets; the number of eggs laid decreased relative to the control, but Vg expression increased. In conclusion, GO prolonged the developmental period of FAWs, decreased fecundity, and led to a decline in the population size. The study provides a basis for the rational use of GO as a pesticide synergist for FAW control.The development and reproduction of the FAWs that were reared on artificial diets containing GO were determined based on age-stage, two-sex life table analysis. The results showed that GO had adverse effects on FAWs. Compared with the control, the duration of the egg stage and instar larval stages increased with increasing GO concentrations; however, the lifespan of male and female adults decreased with increasing GO concentrations. Weights of FAW pupae that were supplied with GO-amended diets increased compared to the control. Intrinsic growth, limited growth, and net reproductive rates of FAWs feeding on GO supplemented diets were significantly lower than the control, while mean generational periods were significantly longer than the control. Expression of genes encoding vitellogenin (


The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity.In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups.Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls . Even after adjusting for age , luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients .High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis, pannus formation, and the destruction of bone and cartilage . There aThe decline in estrogen is the most prominent feature of menopause and has been considered the leading cause of menopausal complications in the past few decades , 5. EstrDue to the negative feedback of the gonadal axis, the levels of FSH also increase during menopause transition . High FSSeventy-nine female patients diagnosed with RA thirty and 50 age-matched healthy control (HC) were included in the study. This study is a prospective analysis. All patients were hospitalized in the Department of Rheumatology, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, and met the 1986 American College of Rheumatology classification criteria. The healthy controls were obtained from the physical examination center of Children’s Hospital of Shanxi and Women Health Center of Shanxi. Participants with premature ovarian failure, bilateral ovariectomy, hormone replacement therapy, contraceptives, corticosteroids > 7.5 mg daily, or malignant tumors were excluded. The controls had no sign of arthritis or other inflammation. The study was approved by the Ethics Committee of Shanxi Bethune Hospital. Informed consent of each participant has been obtained.All data were collected from questionnaires and medical records, including age, onset age, menopause age, body mass index (BMI), patient global assessment (PGA), tender joint count (TJC), swollen joint count (SJC), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The 28-joint disease activity score ESR/CRP (DAS28-ESR/DAS28-CRP) was used to assess the disease activity in RA patients, calculated with PGA, TJC, SJC, ESR, and CRP.The blood of perimenopausal and postmenopausal women was collected randomly. Venipuncture was performed on days 3–6 of a regular menstrual cycle for premenopausal women to exclude cyclical differences in sex hormones. All blood samples were collected after overnight fasting and stored at −80°C immediately. Chemiluminescence  was used for the quantitative determination of sex hormones, including estradiol (E), testosterone (T), progestin (PROG), FSH, luteinizing hormone (LH), prolactin (PRL).All data were analyzed through SPSS software for statistics . Continuous variables were expressed with mean and standard deviation (SD) or median and interquartile according to the normal or nonnormal distribution. Categorical variables are expressed as numbers and percentages; The Student’s t-test or the Mann–Whitney U-test was used to compare the differences between RA patients and healthy controls. A logistic regression model was used to evaluate the FSH in RA and controls with adjustments for age, E2 and T. One-way analysis of variance (ANOVA) was used to compare the clinical parameters among FSH quartiles. A Spearman rank correlation analysis was used to assess the relationship between onset age and menopause age in RA patients. All statistical tests are two-tailed, and p <0.05 is considered statistically significant.Seventy-nine females with RA and 50 age-matched healthy women were included in the study. The sex hormone levels are shown in A logistic regression analysis was conducted to assess whether high FSH affects RA. As shown in We divided RA patients into four groups based on the quartiles of FSH level. As shown in There were 46 post-menopause RA patients included in the study. To address whether menopause age correlates with onset age in RA patients, we performed a correlation analysis, and menopause age was significantly positively correlated with the age of onset of RA patients  (Although the gender and age bias in autoimmune disease (AID) has long been documented, the mechanisms by which it occurs remain unclear. Our previous study surveyed 379 RA patients and found the female to male RA patient ratio was 2.83, and the peak age of RA females was 51-60 years (data not shown). The peak incidence of RA in women was also consistent with menopausal years in other studies . AutoimmMenopause is accompanied by increased GnRH and decreased sex hormone due to ovarian failure. Age is an independent risk of menopause, so age-matched healthy women are selected as controls. In this study, we found that compared with the control group, female patients with RA tend to have higher GnRH and lower sex hormones, which indicates that the prevalence of ovarian failure in RA patients is high. Recently, we conducted a meta-analysis of the assessment of ovarian failure by serum anti-müllerian hormone in RA patients and obtained similar results . For GnRWe performed a multivariate logistic regression analysis to determine whether elevated FSH levels are independently associated with RA. The results showed that high circulating FSH levels were an independent risk factor for RA. After adjusting potential confounders, the risk remains. Mitra Pikwer also reported that high FSH was associated with the risk of RF-negative RA men after adjusting smoking and BMI [OR: 11.5 (1.46 to 91.1)] . AlthougStudies have shown that hormonal status affects the disease characteristics of women with RA. In addition to changes in hormone levels, menopause also leads to increased production of cytokines, such as IL-1, IL-6, and tumor necrosis factor (TNF) , which aSignificant changes were observed in LH in different FSH quartiles because they are similarly regulated and therefore have corresponding physiological changes. RA patients with early age at menopause had higher mean patient global and pain scores and were more likely to be a rheumatoid factor (RF) positive . TherefoOur study also has several limitations. Firstly, the sample size was small. Seventy-nine female RA patients were enrolled in our study, with only nearly 20 patients in each quartile. As a result, no expected trends were found in FSH quartiles 2,3 and 4. Secondly, the impact of RA treatment was not considered. Although in our previous study, DMARDs treatment had no harmful effect on the ovarian function of RA patients , their iIn conclusion, high FSH seems to be a risk factor for RA and is positively associated with its disease activity. Despite the fact that the extragonadal effects of FSH have been studied in various menopausal symptoms, few studies have investigated the function and changes of serum FSH in women with RA. The mechanism of gender and age bias in autoimmune diseases is still not fully elucidated. Our findings provide new insight into the pathogenesis of RA. Inhibition of FSH levels may be a targeted therapy for RA.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the ethical committee of Shanxi Bethune Hospital. The patients/participants provided their written informed consent to participate in this study.XZ, PQ, QG, FW, and XW contributed to the conception and design, and the initial draft of the manuscript. ZL and JP contributed to data analysis and revision. LZ contributed to supervision and editing. All authors contributed to the article and approved the submitted version.This work was supported by the Youth Foundation of Science and Technology Department of Shanxi Province (20210302123448) and the National Natural Science Foundation of China (81771768).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Early maladaptive schemas (EMSs) are themes regarding oneself and one's relationship with others. In schema therapy, 18 EMSs are described that were initially proposed to be clustered in five domains. The current EMS model comprises four domains. However, empirical investigations into the grouping of EMSs have yielded divergent results. The purpose of the present study was to use a meta-analytical approach to examine the higher-order organization of EMSs.N = 13,958, Mage = 16–72.3 years, 64.0% female). The correlations between EMSs were pooled across samples and analyzed using confirmatory factor analysis (CFA) and principal component analysis (PCA).To be included in the statistical analyses, studies had to report the associations between all 18 EMSs using a form of the Young Schema Questionnaire. In a systematic literature review in PsycInfo, Embase, MEDLINE, Web of Science, and Google scholar, 27 studies were identified that reported the associations between EMSs in 33 independent samples (The CFA results showed weak support for any of the previously suggested EMS domains. After PCA, four EMS domains were retained that closely resembled the theoretically proposed organization of EMSs. The four components showed fair to good congruence in the clinical and non-clinical subsamples. However, a model with three EMS domains showed a simpler structure.The results suggest a need for further theoretical and empirical clarification of the higher-order structure of EMSs.https://osf.io/57wyz. The concept of early maladaptive schemas (EMSs) is at the core of schema therapy (ST) , which iSince the first version of the EMS list , EMSs haSeveral studies have examined the higher-order structure of EMSs with exploratory factor analysis (EFA). Other researchers have used confirmatory factor analysis (CFA) to investigate the organization of EMSs into domains e.g., , 24–31].–31.24–31Consensus on the number and organization of higher-order EMS domains is important for theory development and research. Because the EMS domains are thought to be connected to different basic emotional needs, the number and content of EMS domains provide information about the number and specific emotional needs on which EMS theory is built in ST. Further, many studies focus on EMS domains instead of specific EMSs e.g., –34]. Agr. Agr34)]A limitation of individual studies on the organization of EMSs is that the results are influenced by the characteristics of the specific samples. The aim of the present study was to investigate the higher-order structure of EMSs by meta-analytically combining data on the associations between EMSs in different samples. Based on Young's  revised Studies were eligible for the present study if EMSs were assessed with a form of the YSQ and a full correlation matrix of all 18 EMSs in the current schema list was reported in the publication. In addition, because correlations between EMSs can be calculated from factor loadings, studies presenting a complete factor or component loading matrix after EFA or principal component analysis (PCA) with orthogonal rotation were included. When oblique rotation was used or a CFA was performed, the factor correlations had to be reported in order to be included in this study. Furthermore, to be eligible for this study publications had to be available from the university's library or digital repositories and be written in English, German, French, Spanish, or a Scandinavian language.A systematic literature search was conducted on December 10, 2021 (Google Scholar), and on December 11, 2021 . The following key words were used: “Early maladaptive schemas” AND . The search was repeated on May 26, 2022, and more recent results were added. The search results were processed in Zotero, and duplicates were removed before the titles and abstracts of the publications were screened. Finally, full texts were reviewed for tables or figures displaying correlations between YSQ scales or factor loadings. The following information was extracted from the included studies: authors, publication year, publication type , country, sample size, sample type , mean age and standard deviation of the sample, percentage of female participants, version of the YSQ used, and the data provided .https://osf.io/57wyz.The study was preregistered on The statistical analyses were conducted in R (v4.2.0) . First, The pooled correlation matrices were statistically analyzed using CFA and EFA. The domain models in Further, PCAs with 1–5 factors were conducted to investigate the structure of the pooled correlations between EMSs. The hierarchical structure of the different factor solutions was examined using Goldberg's  bass-ackn = 4), followed by Italy (n = 3), Finland (n = 3), Hungary (n = 2), and Germany (n = 2). The total sample size was 13,958 individuals, including 11,024 non-clinical participants, 1,769 clinical participants, and 1,165 participants from mixed clinical and non-clinical samples. The mean age of the samples ranged from 16.0 to 72.3 years, and on average 64.0% were female. Nineteen studies assessed EMSs with the YSQ-S3, one study used the YSQ-L3, and seven studies administered modified previous versions of the YSQ. Translations of the YSQ were used in 22 studies. Correlations between YSQ scales were provided in 21 publications, while four and two publications reported the results from EFAs and CFAs, respectively.The identification of studies is shown in The meta-analytically pooled correlations between EMSs are shown in Global model fit of the different models of EMS organization is displayed in p < 0.05 [p < 0.001]. The Kaiser-Meyer-Olkin (KMO) criterion also suggested that the data were suitable for PCA (KMO = 0.95). For the total sample, Bartlett's test of sphericity was significant at Parallel analysis and the empirical Kaiser criterion suggested extracting two components. Solutions with two, three, and four components had at least three EMSs with component loadings larger than 0.40 and showed a slightly better model fit (SRMR = 0.05) than the one-component solution (SRMR = 0.06). Because the four-component solution was more closely aligned to the theoretical model than the solution with three components, it was decided to retain four components. The full pattern matrix is shown in p < 0.05 for the clinical [p < 0.001] and the non-clinical sample [p < 0.001]. The KMO was 0.95 for both samples, suggesting the suitability of the PCA. Four components were extracted in both samples that were highly similar to the component solution obtained for the total sample  suggested extracting two components. The same result has been reported in previous studies , 19, 21.Similar to the studies of Bach et al.  and YalcThe four components showed satisfactory congruence in the clinical and non-clinical subsamples. However, small differences in the patterns of component loadings appeared between the two samples. For example, in the clinical sample, defectiveness/shame had a higher loading on the impaired autonomy and performance domain than the disconnection and rejection domain. The insufficient self-control/self-discipline and approval seeking/recognition-seeking EMSs loaded almost equally high on the impaired autonomy and performance and the impaired limits domains. These variations raise the question as to whether some YSQ scales are particularly prone to the effects of mood. This explanation is supported by findings that mood induction affects the reporting of EMSs in the YSQ . HoweverThe four-component model was retained because it was most closely aligned to the theoretically proposed groupings of EMSs . HoweverA strength of the present investigation is that it draws on a diverse base of samples. On the other hand, the results should be interpreted in the light of some limitations. Given the large number of investigations into EMSs, the number of studies that could be included in the meta-analysis was moderate, mainly because information about the intercorrelations between EMSs was not provided in many publications. Further, to reduce heterogeneity only studies that used a form of the YSQ to assess EMSs were included. However, the equivalence of the different versions of the YSQ is uncertain, especially with regard to the most recently added EMSs. Some researchers have developed and used their own scales for the approval-seeking/recognition-seeking, negativity/pessimism, and punitiveness EMSs , but thIn conclusion, the results of the present investigation support the organization of EMSs in the four domains proposed by Young  and BachThe author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.