Spalax ehrenbergi) is an extreme. It is exceedingly solitary, territorial, and aggressive. BMRs reside underground, in self-excavated tunnels that they rarely leave. They possess specialized sensory systems for social communication and navigation, which allow them to cope with the harsh environmental conditions underground. This review aims to present the blind mole rat as an ideal, novel neuroethological model for studying aggressive and solitary behaviors. We discuss the BMR’s unique behavioral phenotype, particularly in the context of ‘anti-social’ behaviors, and review the available literature regarding its specialized sensory adaptations to the social and physical habitat. To date, the neurobiology of the blind mole rat remains mostly unknown and holds a promising avenue for scientific discovery. Unraveling the neural basis of the BMR’s behavior, in comparison to that of social rodents, can shed important light on the underlying mechanisms of psychiatric disorders in humans, in which similar behaviors are displayed.On the social scale, the blind mole rat (BMR;  Lynx lynx) (Dipodomys heermanni)  and Damaraland mole-rat (Fukomys damarensis) are eusocial, residing in large underground communal colonies, and are in fact the only two known eusocial species within the Mammalia class (Cryptomys hottentotus) are social, living in small, transient familial groups (Georychus capensis) live alone in solitary burrows . In socnx lynx) , and smaermanni) . Interesermanni) . Even moia class . Highvell groups , and Cap burrows . This va burrows .Spalax ehrenbergi superspecies , represents an extreme. It is an exceedingly solitary and territorial subterranean rodent that lives entirely within self-excavated underground tunnel systems. The BMR, weighing 100–250 g (Mus musculus) and rats (Rattus norvegicus), the most commonly used animal models in neuroscience , of the 00–250 g , can be 00–250 g . Thus fa00–250 g . Here, woscience , are conoscience . We suggoscience .In the course of this review, we explore the wealth of neuroethological opportunities in the BMR, relating to social behavior and interactions, foraging and navigation. We first describe the BMR’s extremely solitary behavior, its foraging and food-caching strategies, and the transient shift in sociality it needs to make with the onset of the breeding season. We also describe the BMR’s unique sensory adaptations to the underground habitat , includiWith the exception of short mating and lactating periods during the winter (the wet season), male and female blind mole rats reside alone throughout the year, patrolling their tunnels and defending their territories from conspecifics and congenerics . For theLike other territorial animals, the spatial ecology and social organization of the blind mole rat can be considered a type of social communication network. In this network, repeated communication signals detected from a distance may advertise locations of neighbors and function to maintain boundaries and conspecific spacing . Thus, tBMRs are seasonal breeders , for whoA female will respond to the male’s courtship gestures based on her sensory perception and prior experience, to ultimately allow a typically aggressive male to approach, and subsequently mate with . To dateMicrotus ochrogaster), alteration of both temperature and photoperiod caused regression in synthesis of gonadotropin-releasing hormone, and in their reproductive function (Microtus townsendii), the addition of a specific plant metabolite during the non-breeding season, increased serum follicle-stimulating hormone levels and the size of reproductive organs  , where fWhile blind mole rats appear as if they have no eyes, they do possess rudimentary eyes (less than 1 mm in diameter), that are covered by furred skin . The lenIn mammals, light perceived through the retina uses the common photoreceptors (i.e. rods and cones) for image formation, and the photoreceptor melanopsin for the non-image forming system. Melanopsin is the driving force for the circadian timing system, that initiates the animal’s physiology and behavior in distinct times and periods . The BMRInsights on light perception in the BMR emphasize its relevance as a model for studying re-routing of sensory modalities into processing areas of other sensory modalities, after evolution has neutralized its original output. Such cross-modality reorganizations in animal models are often induced artificially . However, the visual system of the blind mole rat is naturally and congenitally adapted to life in the dark, rendering it a very attractive subject for studying evolutionary plasticity in the central nervous system (CNS) and for revealing the mechanism of neuronal compensation.Fukomys anselli) demonstrated impaired magnetic sensing, supporting the hypothesis that in mole rats, magnetoreception receptors are located in the cornea (Fukomys amatus), that was shown to be independent of light in its perception of the earth’s magnetic field , or for detection and communication with conspecifics . HoweverCavia porcellus) is –9 dB SPL (sound pressure level)  , while ie level) . Resultse level) . Additioparation . Blind mparation . The lowparation . The BMRparation .Fukomys mechowii) were demonstrated to have a repertoire of 14 call types as determined by behavioral context, such as teeth-fencing and predator alarm, and by spectro-temporal features  signals . The useA BMR produces vibrational signals by drumming on the ceiling of its tunnel with the large, flattened portion of its head, producing bursts of head drums  . SeismicThe general understanding of the behavioral discrimination and sensitivity of perception of vibrational waves in the subterranean environment is greatly lacking . The senIn addition to the auditory cortex, it was further shown that the BMR’s somatosensory cortex also extends far into the occipital cortex . This fiIn mammals, oscillating signals passed to the animal by direct contact with a solid substrate can be perceived by both auditory and somatosensory mechanisms. The role of the auditory system in detection of seismic signals was discussed earlier . Blind mole rats have been suggested to detect vibrational signals through the somatosensory system in addition to the auditory system. Kimchi and colleagues demonstrated that BMRs use seismic signaling as an echolocation behavior . In fielOlfaction, the sense of smell, plays an important role in detection of food, identification of conspecific territories and recognition of mates. For an animal as aggressive and territorial as the blind mole rat, which is also visually blind, the ability to identify odors from the surroundings is highly important in order to avoid intraspecific aggressive encounters. BMRs possess dorsoventrally flattened, wide, snouts  , that asBathyergidae), which show postnatal vomeronasal epithelium (VNE) length increase of less than one-fold  and type 2 (V2Rs) . While VPheromonal signaling in the blind mole rat is used in short-distance social communication . In the Urine and feces are other prominent sources for odor stimuli used by many mammalian species in a variety of behaviors . Male BMVarious neuromodulators were shown to be involved in aggressive behavior and sociability in mammalian species in general, and in rodent species in particular . In thisLasiopodomys brandtii), mandarin voles (Lasiopodomys mandarinus) (Tscherskia triton)   and grea triton) . However triton) , Ansell’ triton) , and nak triton) .In the blind mole rat, no data was published thus far regarding the hypothalamic population and distribution of OT neurons. Preliminary data recently established in a comparative study in our lab, found that when considering the differences in brain size, the BMR’s PVN contains significantly lower numbers of OT neurons compared to mice. Furthermore, we found no indication of sex differences in the number of OT cells in the PVN of male and female BMRs (unpublished data). Moreover, while it is often assumed that male BMRs are more aggressive than females, our observations suggest similar levels of aggression in both sexes (unpublished data), which might be related to the sex similarities in OT distribution.There are many evidence that link social cues with the number of OT and AVP cells in the hypothalamus. The presence of a social stimulus was shown to activate the OT system to promote adaptive social behavior responses; a study of the eusocial NMR that examined the effect of social status on the number of OT neurons, revealed that subordinate individuals have more OT-producing neurons in the PVN compared to breeding individuals . PeripheShank3b KO mice, a common mouse model of ASD, which present abnormal social behaviors, have reduced numbers of OT neurons in the PVN  and hindbrain . With inThe effects of CRF and its receptors in regulation of male aggression in rodent species depend on the site of its administration, dosage and experimental paradigm. In some studies, CRF administration, or elimination of one of its ligands or receptors (by a genetic knock-out), was shown to facilitate or decrease aggressive behavior , while iIn a comparative study, Coen found considerable differences in CRF abundance and receptor binding in the telencephalon, between the eusocial NMR and the solitary Cape mole rat . These dFurther research into the role of the OT, AVP, and CRF systems in sociability of the solitary BMR, and their comparison to findings in the eusocial NMR, could potentially add to our understanding of the neuromodulators and circuits governing anti-social behavior.In his review from 1991, Spalax ehrenbergi is deprived of visual inputs, and thus compensates via the diversion of the visual modality to the auditory modality. Cross-modal neuroplasticity in animal models is induced, in most cases, by experimental procedures . NeuroeSpalax ehrenbergi genomic assembly has been deposited for a single female BMR (In conclusion, a handful of animal models for the study of diverse biology and neurobiology is not sufficient. We have recently discussed the main biases in social behavioral research, and showed that science in general, and behavioral and neurobiological studies in particular, tend to rely mostly on male mice in a small confined laboratory environment . Howevermale BMR . In addimale BMR , and scRmale BMR . An addimale BMR . This is


Fritillaria L. medicinal plants are unique Chinese medicinal ingredients, but the continuous cropping obstacles formed in the artificial planting process is severely harmful to the growth and development of these medicinal plants. In this review, we summarized the current species and distribution of Fritillaria L. in China, and analyzed the changes in microbial diversity (mainly among bacteria and fungi) in the rhizosphere of these plants under long-term continuous cropping. The fungi showed an increasing trend in the soil rhizosphere, resulting in the transition of the soil from the high-fertility “bacterial type” to the low-fertility “fungal type” as planting years increased. Furthermore, the interaction between Fritillaria L. medicinal plants and the rhizosphere microorganisms was reviewed, and promising applications for the rhizosphere microbiome in the cultivation of Fritillaria L. medicinal plants were suggested. It is expected that this review will facilitate the in-depth understanding of rhizosphere microorganisms in the growth, accumulation of active ingredients, and disease control of Fritillaria L.The soil’s rhizosphere is a highly active place where the exchange of substances and information occurs among plants, soils, and microorganisms. The microorganisms involved are crucial to the activities of plant growth and development, metabolism, and reproduction.  Fritillaria L., a valued traditional Chinese herbal medicine, contains diterpenoids, steroids, alkaloids, polysaccharides, which have broad applications in health care products, food, Chinese herbal formulas, and everyday chemical industries. This plant has the benefits of reducing phlegm, relieving coughs, reducing heat, moistening the lungs, improving blood stasis, and dispersing knots  and Web of Science. Fifty-seven literature was searched in CNKI, and 57.9% of which was published from 2016 to 2021, six literature was searched in Web of Science. It is expected that this review will contribute to further understand the involvement of rhizosphere microorganisms in the growth of Fritillaria medicinal plants and the accumulation of alkaloids, which are the most important active ingredients of Fritillaria.This review article systematically describes the research results on the rhizosphere microorganisms associated with Fritillaria L. from different places of origin have varied in recent years. To meet the requirements of the market, it is imperative to cultivate Fritillaria L. medicinal plants artificially. Five types of Fritillaria L. plants present in the Chinese Pharmacopoeia  are collected; these include Fritillaria ussuriensis Maxim, Fritillaria pallidiflora Schrenk, Fritillaria thunbergia Miq., Fritillaria hupehensis Hsiao et K. C. Hsia, and Fritillaria cirrhosa D. Don. The specific growth environment and distribution of different Fritillaria medicinal plants are shown in Fritillaria medicinal plants have wide distribution range and high adaptability. It has been proven that it is feasible to breed wild Fritillaria medicinal plants , Proteobacteria (22.00%–28.80%), Acidobacteria (13.82%–20.86%) and Chloroflexi (8.43%–15.08%) belonging to the dominant phyla, and the continuous planting of Fritillaria kansuensis for 5 years would significantly reduce the diversity of bacterial communities in the soil rhizosphere. Fritillaria thunbergii.Using the high-throughput sequencing technology, from the phylum level analysis, it can be seen that the bacterial community within the soil rhizosphere was mainly composed of Proteobacteria Acidobacteria, oroflexi . Among tncreased . Wu , phosphate-solubilizing bacteria, and nitrogen-fixing bacteria, which may because of the increase in the relative abundance of saprophytic fungi. Phosphate solubilizing bacteria can convert insoluble phosphorus into effective phosphorus that can be absorbed and subsequently used by plants. According to the different substrates of phosphate-solubilizing bacteria, they could be divided into organic phosphorus bacteria and inorganic phosphorus bacteria , which iF. taipaiensis in the previous report revealed that these varied with different growth years , Glomus versiforme (GV), Glomus mossae (GM), and Glomus aggregatum (GA). AMF alone could significantly increase the fresh weight, dry weight, and drying rate of F. taipaiensis bulbs, and increase the contents of Fritillarin A, sibelline glycoside, Fritillarin B, Fritillarin, and alkaloids in the bulb. AM fungi could increase the content of inorganic elements in the rhizome and soil of F. ussuriensis, and also enhance the enrichment ability of inorganic elements, thereby improving the growth and development of F. ussuriensis, and promoting the accumulation of nutrients in medicinal materials  in the bulb first increased and then decreased. Correlation analysis showed that the Chao1 index and Shannon index among the bacteria were positively correlated with the content of monomer alkaloids and total alkaloids, indicating that the soil bacterial community was closely related to the content of alkaloids. Furthermore, the secondary metabolites produced by Fritillaria cirrhosa D. Don displayed high antioxidant activity. For example, the low polar substances extracted by petroleum ether had weak ABTS free radical scavenging activity, whereas the high polar substances extracted by solvents such as n-butanol and ethyl acetate had high ABTS free radical scavenging activity .ous harm . This maal value . Using m rapulum  and Fusaoeruleum , respect methods . The pat disease . But theys rosea . BotrytiThe plant microbiome, also known as the pan-genome, refers to the study of the role of the rhizosphere microbial community in the growth of host plants in a holistic manner. It plays an irreplaceable role in the ecological environment and agricultural production , which iAccording to the varied distribution of microorganisms on the root system, the rhizosphere microbiome could be divided into the three categories of rhizosphere microbiome, root surface microbiome, and root internal microbiome . Due to A large number of studies have indicated that the rhizosphere microbiome played an important role in promoting the growth and tolerance of host plants. These are mainly divided into two methods of negative interaction such as rhizosphere microorganisms infecting the host to cause diseases or competing with the host for nutrition, and positive interaction such as rhizosphere microorganisms promoting growth, stress resistance, and disease resistance . This inPseudomonas fluorescens in rhizosphere microorganisms inhibited Sclerotium rolfsii by more than 75% (P. fluorescens (WCS417r) that colonized the Arabidopsis rhizosphere could upregulate the expression level of defense-related genes of the host plant pathogen (Pseudomonas syringae pv tomato)  . In addi tomato) . It coulFritillaria medicinal plants. Therefore, the rhizosphere microorganisms of Fritillaria plants have received much attention, which not only helps to solve the practical problems of disease prevention among Fritillaria medicinal plants, but also improves the yield and quality of these plants. It also helps to clarify the interaction mechanism between Fritillaria medicinal plants and beneficial or harmful microorganisms in the rhizosphere. Based on the authors’ knowledge, future research on rhizosphere microorganisms of Fritillaria medicinal plants should focus on the following aspects.In this review article, rhizosphere microorganisms were found to be closely related to the propagation, metabolism, and growth of Fritillaria, it is suggested to combine the pure culture method and free culture method. Moreover, there are few reports on the diversity of the rhizosphere microbial population of Fritillaria medicinal plants. Because most of the reports are only at the pure culture stage, in the future more attention should be carried out to explore the impact of different Fritillaria medicinal plant varieties, growth years, environmental conditions, and climate factors on the rhizosphere microbial diversity of these plants. The relationship between the rhizosphere microorganisms of Fritillaria medicinal plants and their growth should be understood in detail.Presently, the traditional method used on rhizosphere microorganisms is the pure culture method. With the development of molecular biology technology, the free culture method is widely used in the research of rhizosphere microorganisms of medicinal plants. However, the free culture method cannot obtain live strains, nor provide strains for the research of growth-promoting bacteria in the rhizosphere. Therefore, in the research of rhizosphere microbial diversity of Fritillaria medicinal plants and rhizosphere microorganisms is not clearly understood. In the future, more attention should be paid to the growth-promoting mechanism and the mechanism of the continuous cropping obstacle of Fritillaria medicinal plants. Moreover, the development of biocontrol agents should be strengthened. The perennial Fritillaria medicinal plants have suffered from widespread and serious underground diseases and insect pests, resulting in a decline in the quality of Fritillaria Chinese medicinal materials. Therefore, microbial agents that are safe, efficient, and pollution-free should be developed, which can improve the soil environment, and the output and quality of Fritillaria medicinal plants (The mechanism of interaction between l plants .Fritillary medicinal plants have been reported (Fritillaria may be speculated from the incidence of other Fritillaria plants, but the pathogen of the same disease in different Fritillaria plants are not exactly the same. Therefore, it is necessary to strengthen the research on the pathogenic microorganisms of diseases and insect pests of Fritillaria. Moreover, it is necessary to strengthen the research on rhizosphere microorganisms of diseased plants and healthy plants, explore which changes of rhizosphere microorganisms are related to the occurrence of medicinal plant diseases of Fritillaria, and screen biocontrol strains from rhizosphere microorganisms. Moreover, it is necessary to strengthen the research on rhizosphere microorganisms of diseased plants and healthy plants, explore which changes of rhizosphere microorganisms are related to the occurrence of medicinal plant diseases of Fritillaria, and screen biocontrol strains from rhizosphere microorganisms.At present, pathogens of main diseases of Fritillaria medicinal plants are relatively isolated, thus it is necessary to learn from the research methods between other medicinal plants and rhizosphere microorganisms to understand the interaction mechanism between Fritillaria medicinal plants and rhizosphere microorganisms. In summary, it is expected that this review article will facilitate the development of Fritillaria medicinal plants.Currently, it would be more meaningful to develop more field applications for rhizospheric microbes rather than potted plants. The research methods on the rhizosphere microorganisms of


Long et al. studies, determined the scientometric research on exosome in neuroscience between 2005 and 2021. Analysis included the number of research articles published, citation bursts, and journal impact. Overall, the scientometric analysis was performed from 856 articles which suggested a significant increase of exosome research in neuroscience using several tools like Carrot2 online system, a clustering and visualizing platform to identify Research Topics about exosomes in neuroscience. These efforts reveal that Alzheimer's disease and mesenchymal stem cells are the major research interests of exosome research in neuroscience and suggest that exosome-based therapeutic technology might be state-of-the-art in the foreseeable future.Extracellular vesicles famous by the name of exosomes are potential diagnostic and therapeutic markers for almost all types of diseases. However, very little is known about exosomes derived from brain tissue because of minimal access to the inner cranial tissues, selective permeability of blood-brain barrier, and delicacy of neuronal tissues. Nevertheless, development of research on neuronal exosomes is significantly rising. Moussa et al. focused on characterizing neuronal exosomes from blood plasma, suggesting NCAM-positive EVs may be suitable neuronal markers in exosomes. This study utilizes brain organoids and stem cells to demonstrate NCAM as a neuronal biomarker in exosomes.It is still challenging to separate neuronal exosomes from plasma or serum blood to develop diagnostic markers for many known neurodegenerative diseases. The research article by Gassama and Favereaux summarized EVs' physiology, pathology, and therapeutic perspectives in the CNS. They outlined the role of EVs released from Neurons and non-neuronal cells  as our primary source for inter-cellular communication. In addition to the physiological function, Huo et al. added the value of intercellular communication by the neuronal-derived exosomes. Neuronal EVs are shown to carry chemokines, transfer secondary messenger molecules to the cells, and contain ion channels such as AMPA receptors and Synaptotagmin4. This transfer of functional proteins and ion channels changes the post-synaptic plasticity in the recipient cells. The EVs released from neurites during depolarization is enriched with miR-132, known to regulate the Notch signaling pathway. EVs released from Astrocytes show the maturation of oligodendrocytes, neurite growth, neurite protection during oxidative stress and possess unique surface markers.Brain comprises both neuronal and non-neuronal tissues; this Research Topic focuses on the function of brain-derived extracellular vesicles (EVs) in the central nervous system (CNS) and their role in the diagnosis and prognosis of brain pathologies. Gassama and Favereaux shed light on pathological implications of EVs containing miRNA and pathology-related proteins such as amyloid proteins, alpha-synuclein, or tau-protein that can propagate in surrounding tissues or initiate an undesired epigenetic regulation in recipient cells. Again, contrary to the adverse effects of EVs, EVs could be the leading source for diagnostic markers of CNS pathology such as Glioblastoma, Alzheimer's disease, Huntington's disease, and Multiple sclerosis. In addition, Gassama and Favereaux summarized the therapeutics of EVs to deliver drugs across the blood-brain barrier such as siRNA and Curcumin. Huo et al. added the valued information on the effect of external stimuli causing neurons' excessive secretion of exosomes. These influences are mainly from the depolarization of neurons. Exosomes derived from Microglia exposed to LPS showed exosomes containing IL-4, extracellular ATP activating P2X7 receptors initiate secretion of exosomes from microglial cells.On the contrary, Huo et al. in their review paper, focused on the exposure of cytotoxic proteins to astrocytes releasing exosomes rich in PAR-4 that promote apoptosis, and also discussed the function of amyloid, ceramide, and prions in the regulation of exosome secretion which has a crucial role in neuroprotection. Also, Huo et al. discussed the role of exosomes in three major neurodegenerative diseases: Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis. Stroke is a cerebrovascular accident or transient ischemic attack in which blood flow to brain is blocked leading to immediate death or paralysis. As such, there are no clinically approved biomarkers to identify early symptoms of a stroke. The review of Xu et al. focused on exosomal miRNA studies in stroke patients. They summarized the outcome of clinical studies for developing the diagnostic biomarker of ischemic stroke. This study also covers the role of miRNA in the pathogenesis of stroke by cerebral Ischemia. Mainly, animal and in vitro studies are employed to understand miRNA's effect and underlying mechanism in a neuro-protective role, such as promoting angiogenesis, protecting from oxidative stress, and inhibiting apoptosis.Similarly, astrocytes released exosomes showed specific markers like glutamine aspartate transporter (GLAST) and glutamine synthetase (GLUL). Furthermore, studies show free ATP bind to P2X7R induces IL-1β in astrocyte-derived exosomes, and exposure of exosome to neurons initiate the differentiation of dendrites and synapses. In addition, Gamage and Fraser discusses causes of prenatal injury, the injury outcome, mainly cerebral palsy, and the possible treatment with extracellular vesicles isolated from mesenchymal stem cells. Only a limited number of studies are employed using animal models, which shows EVs have a significant therapeutic effect in repairing damage associated with prenatal brain injury. This review also discussed the uptake of exosomes or EVs by neurons, glial cells, and their downstream signaling effects. Furthermore, Gamage and Fraser discussed the circulation of exosomes derived from fetal CNS into maternal blood; a potential biomarker for early prenatal brain damage.Preterm babies born are at high risk to brain injuries causing permanent motor disabilities. The ability of exosomes to cross the blood-brain barrier likewise crosses the placental barrier. A comprehensive review by Overall neuronal exosome inquiries reveal the birth of a new field in neuroscience that will contribute to a better understanding of neuronal communication that may ultimately provide more comprehensive options for early diagnosis and better therapeutics.SQ wrote the manuscript. AP and IA revised the manuscript and gave input. All authors contributed to the article and approved the submitted version.Author AP was employed by Hamad Medical Corporation. The remaining 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.


Based on the antecedent variable  and the outcome variable (creative deviance) on the individual level, we introduce mediating variables (positive impression management motivation and harmonious innovation passion), integrate moderating variables  to construct the conceptual model and theoretical framework of the influence mechanism of playfulness personality on creative deviance of employees. Based on the questionnaire survey data of employees in high-tech enterprises, this study adopts the nonparametric percentile Bootstrap method based on deviation correction to empirically discuss the influence mechanism of employee playfulness personality on employee creative deviance. The empirical analysis results show that employee playfulness personality has a significant positive influence on employee creative deviance. Positive impression management motivation and harmonious innovation passion partially mediate the relationships between employee playfulness personality and creative deviance. Employee growth need strength negatively moderates the relationships between positive impression management motivation and employee creative deviance. The stronger the employee growth need strength, the weaker the mediating effect of employees' playfulness personality on employee creative deviance through positive impression management motivation, and there is a moderated mediating effect. With the increasingly fierce market competition, innovation occupies the market, which becomes the focus of enterprise decision-making. Managers also gradually realize that innovation can promote the rapid and effective development of enterprises, and encourage employees to innovate by means of material interest incentives, social-psychological incentives, and work incentives. However, due to the limited enterprise resources, managers will finally adopt and support a small number of innovative ideas according to the enterprise development strategy, enterprise vision and market orientation, not all innovative ideas of employees will be accepted. When innovative ideas of employees are not supported by the leaders, giving up the original ideas is a routine behavior of the employees. But it will also occur after the ideas are rejected by the leaders, employees violate the clear stop instruction and continue to adhere to their ideas for innovation privately or publicly, that is, creative deviance  and professional mission sense, constructs the conceptual model of the influence mechanism of employee playfulness personality on employee creative deviance from the perspective of playfulness personality, the variables in the conceptual model are all on the individual levels (employee levels). Based on the questionnaire survey data of employees in high-tech enterprises, this study adopts the nonparametric percentile Bootstrap method based on deviation correction to carry out empirical analysis of the influence mechanism of playfulness personality on employee creative deviance, empirically explores the mediating function mechanism and the moderating function mechanism through the influence path, influence effect and influence process of playfulness personality on employee creative deviance, demonstrates the mediating hub function of positive impression management motivation and harmonious innovation passion, expounds the moderating function  of employee GNS and professional mission sense, and finally extracts and forms the moderation mediating function model, deeply refining the moderation mediating effect.The theoretical research results and empirical analysis conclusion will provide theoretical basis, theoretical significance and practical enlightenment for promoting employee creative deviance in high-tech enterprises, improving employee innovation behavior and performance, achieving the purpose of improving organizational innovation performance and enhancing organizational performance of high-tech enterprises.Lieberman  first prCreative deviance, proposed by Mainemelis , referreIn general, bootlegging is an innovative behavior that is carried out without the consent or even with the ignorant of leaders when the self subjectively believes that their own innovative ideas are beneficial to the enterprise  and the moderated research hypotheses (H8 and H9), the moderated mediating research hypotheses (H10 and H11) are proposed:H10: The stronger the moderating effect of professional mission sense, the weaker the mediating effect of harmonious innovation passion on the relationships between employee playfulness personality and employee creative deviance. There exists the moderated mediating roles and the moderated mediating effects.H11: The stronger the moderating effect of employee GNS, the weaker the mediating effect of positive impression management motivation on the relationships between employee playfulness personality and employee creative deviance. There exists the moderated mediating roles and the moderated mediating effects.According to the above research hypotheses H1–H11, this study sets the antecedent variable and the outcome variable as playfulness personality and creative deviance respectively, takes the mediating variables as positive impression management motivation and harmonious innovation passion, takes the moderating variables as employee GNS and professional mission sense, conceptual model of the influence mechanism of employee playfulness personality on employee creative deviance is constructed, as shown in This study takes the employees of large and medium-sized high-tech enterprises in eastern China as the investigation objects. All employees are engaged in the working field of R&D and innovation. The questionnaires are distributed by means of on-site interview and on-site distribution. Researchers distribute and collect questionnaires at three different time points from January 2019 to October 2019. The first time point questionnaire investigation refers to playfulness personality, employee creative deviance and control variables (the respondents information and the respondents' enterprises information). The second time point questionnaire investigation refers to positive impression management motivation and employee GNS. The third time point questionnaire investigation refers to harmonious innovation passion and professional mission sense. The interval between each investigation is at least 1 month. At different time points, the questionnaire data collected for different variables and different control variables can accurately match each respondent.A total of 360 questionnaires are distributed and 342 questionnaires are recovered. Excluding 53 questionnaires with incomplete questions and completely consistent answers, 289 questionnaires are effective, and the effective rates of the questionnaires are 80.28%, the relevant statistical analysis results and summary results of the control variables and demographic characteristic variables of questionnaires are shown in Refer to relevant literatures home and abroad, this study generates the initial scales. The scales used in this study mainly refer to the more mature scales in the domestic and abroad research literatures and foundations, which are modified in combination with the research purpose and cultural situation. The questionnaires are in the form of Likert 7 scale, 1 is completely inconsistent and 7 is completely consistent. This study further tests the content accuracy, logicality and validity of the scales through two-way back translation and two-way mutual translation in order to determine the final scales. Firstly, doctors, candidates, scholars and experts in relevant fields are invited to translate the Chinese scales into the English scales, translate the English scales into the Chinese scales. Meanwhile, different doctors candidates, scholars and experts in relevant fields are invited to translate the English scales into the Chinese scales, translate the Chinese scales into the English scales. Secondly, considering cultural differences and situational factors, the experts in relevant fields and middle-senior managers of high-tech enterprises are invited to deeply check the consistency of the above two-way back translation results and two-way mutual translation results in order to avoid the language inconsistency, unclear sentences and illogical statements. The scales pass the content accuracy, logicality and validity test, the scales have relatively good internal consistency.The measurement of playfulness personality is based on the scales of scholars Yu et al.  and HuanThis study adopts the measurement scales of creative deviance of scholars Lin et al. . The scaFor the measurement of harmonious innovation passion, we select the harmonious passion part of the scales of harmonious passion and forced passion developed by scholars Sirén et al. , and theThe scales and the corresponding items are in This study adopts structural equation modeling methods to test the common method bias. Single factor model, two factors model, three factors model, four factors model, five factors model, and six factors model are constructed according to structural equation modeling methods. The goodness of fit indexes of single factor model, two factors model, three factors model, four factors model, five factors model, and six factors model are seen in t-test on the differences in the mean values of the core variables . The t-test results show that as for the early-recovery sample and later-recovery sample, there are no significant differences among the mean values of six variables, the p values range from 0.13 to 0.25, which are higher than the critical value of 0.1. Compare the response questionnaires with non-response questionnaires, this study conducts t-test on the differences of the eight control variables  of the questionnaires. The same number of response questionnaires (40 questionnaires) and non-response questionnaires (40 questionnaires) are randomly selected. The t-test results show that for response questionnaires and non-response questionnaires, there are no significant differences in the control variables among the response questionnaires and non-response questionnaires, the p-values range from 0.23 to 0.36, which are higher than the critical value of 0.1. In summary, there is no serious non-response bias in this study.Compare the sample recovered in the early stage with the sample recovered in the later stage, this study conducts a After the theoretically uni-dimensional scales, we further use Mplus software to conduct confirmatory factor analysis of the scales and CFA test on each measurement model, and the output CFA results of the scales are shown in The combination reliability (CR) and convergence validity (AVE) are calculated according to the factor loading obtained in p < 0.05, and the research hypothesis H1 is supported.This study adopts the nonparametric percentile Bootstrap method based on deviation correction, and uses the macro program of process confidence interval in SPSS software (PROCESS Procedure for SPSS Version 3.2), and sets the number of Bootstrap operation samples as 5,000, takes the confidence level and confidence interval as 95%. The test results of the main effect are seen in p-value is < 0.05, employee playfulness personality has a significant promoting effect on positive impression management motivation and harmonious innovation passion (Hypothesis H5 and hypothesis H2 are supported). The path coefficients of positive impression management motivation and harmonious innovation passion on employee creative deviance are 0.385 and 0.200, respectively, and the significance level is <0.05, positive impression management motivation and harmonious innovation passion have significant positive influences on creative deviance (Hypothesis H6 and hypothesis H3 are supported). According to the test results of direct effect, indirect effect and total effect in p is higher than 0.05). To sum up, the research hypotheses that H4 and H7 are supported, harmonious innovation passion plays the mediating role between employee playfulness personality and employee creative deviance, and positive impression management motivation plays the mediating role between employee playfulness personality and employee creative deviance.This study adopts the nonparametric percentile Bootstrap method based on deviation correction, uses the macro program of the process confidence interval in SPSS software (PROCESS Procedure for SPSS Version 3.2) and sets the number of Bootstrap operation samples as 5,000, takes the confidence level and confidence interval as 95%. The test results of the mediating effects are seen in This study adopts the nonparametric percentile Bootstrap method based on deviation correction and uses the macro program of the process confidence interval in SPSS software  value of goodness of fit index is 0.0069, F-value is 5.5163, p-value is 0.0195, p < 0.05, under the conditional action of low-level, medium-level and high-level moderating variables, the values of moderating effect are 0.5444, 0.4329, and 0.3437, p-values are 0.000, p < 0.05, and the corresponding confidence intervals , , , and the confidence intervals do not include 0. To sum up, the research hypothesis of GNS moderating effect is supported by H9, and employee GNS negatively moderates the relationships between positive impression management motivation and creative deviance.The hierarchical regression analysis model 1 with moderating variable GNS, mediating variable YXDJ, and no product interaction term is constructed, and the hierarchical regression analysis model 2 with moderating variable GNS, mediating variable YXDJ and product interaction term GNS x YXDJ is constructed. Both hierarchical regression analysis models take CRDE as the dependent variable. The test results in p-value is 0.1215, the p-value is higher than the specified significance level of 0.05, the corresponding confidence interval is , the confidence interval includes 0, and the product interaction term has no significant negative influence. Hierarchical regression analysis model 4 is compared with hierarchical regression analysis model 3, the R2 change value (R2-chng) of the goodness of fit index is 0.0034, F-value is 2.4117, p-value is 0.1215, and the significance level is p > 0.05. To sum up, the research hypothesis of SMG moderating effect H8 is not supported, and professional mission sense does not have a negative moderating effect on the influence of harmonious innovation passion on employee creative deviance.The hierarchical regression analysis model 3 with moderating variable SMG, mediating variable CXJQ and no product interaction term is constructed, and the hierarchical regression analysis model 4 with moderating variable SMG, mediating variable CXJQ, and product interaction term SMG × CXJQ is constructed. Both hierarchical regression analysis models take CRDE as the dependent variable. The test results in t-value is 7.5698, p < 0.001), the relationships between positive impression management motivation and creative deviance are strengthened. When GNS is high, the effect of positive impression management motivation on employee creative deviance is low , the relationships between positive impression management motivation and creative deviance are weakened.This study further draws the moderating and interaction effect figure according to the moderating and interaction effect drawing steps and the key analysis steps of simple slope . To sum up, when employee GNS is weak, the mediating effect of positive management motivation on the relationships between employee playfulness personality and employee creative deviance is strong, the weaker the employee GNS, the stronger the mediating effect of playfulness personality on employee creative deviance through positive impression management motivation, and the moderated mediating effect is significant, the research hypothesis H11 is supported.This study further adopts the nonparametric percentile Bootstrap method based on deviation correction, and uses the macro program of process confidence interval in SPSS software (PROCESS Procedure for SPSS Version 3.2), and sets the number of bootstrap operation samples as 5,000, takes the confidence level and confidence interval as 95%. The test results of the moderated mediating effect of research hypothesis H11 is seen in Due to that the research hypothesis H8 of SMG moderating effect is not supported, and the professional mission sense does not have negative moderating effect on the influence of harmonious innovation passion on creative deviance, it is not necessary to test the moderated mediating effect of research hypothesis H10, and research hypothesis H10 is not supported.According to the above data analysis and research hypothesis test, the summary of specific research hypothesis test results are obtained, as shown in This study introduces the mediating variables (positive impression management motivation and harmonious innovation passion), and integrates the moderating variables  to construct the conceptual model of the influence mechanism of playfulness personality on employee creative deviance. This study adopts the non-parametric percentile Bootstrap method based on deviation correction to carry out an empirical analysis of the influence mechanism of employee playfulness personality on employee creative deviance. The main results of influence mechanism of employee playfulness personality on employee creative deviance are seen as follows:Main effect. The main effect of employee playfulness personality on employee creative deviance is significant, and employee playfulness personality can significantly promote employee creative deviance.Mediating effect. Harmonious innovation passion and positive impression management motivation play partial mediating roles in the relationships between employee playfulness personality and creative deviance, employee playfulness personality has an indirect influence on employee creative deviance by affecting harmonious innovation passion and positive impression management motivation. On one hand, playfulness personality is a personality trait that enables employees to show positive willingness to participate in innovation activities, under the action of strong harmonious innovation passion, the willingness to participate can promote the transformation of employee innovative ideas. On the other hand, the personality trait of being active and willing to work is easy to obtain good impression in the psychology, mentality, mind of leaders and other employees, and put emphasis on controlling impression of each other. After the rejection of their own innovation concepts, the positive and optimistic personality trait is beneficial to activate the motivation and psychology of obtaining positive impression, urges employees to continue to implement innovation activities against the willingness of leaders. When carrying out creative deviance, they will take the initiative to spend more time and energy, make use of their personal resources and enterprise resources, and continuously improve and optimize their own innovative ideas, framework and design thinking, achieve innovation recognition and innovation performance.Moderating effect. Employee GNS has an influence on creative deviance, and employee GNS significantly negatively moderates the influence of positive impression management motivation on creative deviance. Weaker employee GNS can moderate the influence of positive impression motivation on creative deviance.The moderated mediating effect. Driven by moderating variable employee GNS, the mediating effect of positive impression management motivation between the relationships of employee playfulness personality and employee creative deviance is gradually weakened. As the buffer variable and boundary condition, employee GNS weakens the mediating link and bridge role of positive impression management motivation in the relationships between employee playfulness personality and employee creative deviance. Compared with employee creative deviance to obtain positive impression, employees with high growth need strength motivation pay more attention to the existing routine and standardization work, and focus on participating in normal innovation activities in the existing work field, so as to inhibit the emergence of creative deviance behavior.This study sets the perspective of employee playfulness personality, takes the antecedent variable as playfulness personality in order to deeply explore the antecedent variable of employee creative deviance, demonstrate the rooted influential variable of creative deviance, verify the formation mechanism and driving mechanism of employee creative deviance. The main effect indicates that playfulness personality has a positive influence on constructive creative deviance, which exerts significantly positive rooted effect. The research results expound and enrich the theoretical framework and conceptual model of the antecedent variable of creative deviance on the individual level, echo, respond, advocate the theoretical research achievements of creative deviance with positive and constructive effect, increase the theoretical research basis and foundation of the outcome variable of playfulness personality, enhance the applicable scope of playfulness personality and the influence of individual positive personality trait on innovation aspects and new innovation models.This study selects mediating variables as positive impression management motivation and harmonious innovation passion, improves and enriches the conceptual model and theoretical analysis framework of the influence mechanism of playfulness personality on employee creative deviance from the perspectives of mediating variables (positive impression management motivation and harmonious innovation passion). Furthermore, we adopt the non-parametric percentile Bootstrap method based on deviation correction, implements Bootstrapping operation with a view to empirically exploring the mediating function mechanism of the influence process and influence path of playfulness personality on employee creative deviance, deeply refining the positive mediating effects of the relationships between playfulness personality and employee creative deviance, enriching the theoretical research basis, foundation and relevant results of playfulness personality and employee creative deviance, enhancing the applicability and effectiveness of the mediating variables (positive impression management motivation and harmonious innovation passion) of the relationships between playfulness personality and employee creative deviance.This study selects moderating variables  as boundary conditions and situational factors, improves and enriches the conceptual model and theoretical analysis framework of the influence mechanism of playfulness personality on employee creative deviance from the perspectives of moderating variables . Furthermore, we adopt the nonparametric percentile Bootstrap method based on deviation correction, implements Bootstrapping operation with a view to empirically exploring the moderating function mechanism of the influence process and influence path of mediating variables (positive impression management motivation and harmonious innovation passion) on employee creative deviance, deeply refining the positive moderating effects of the relationships among mediating variables (positive impression management motivation and harmonious innovation passion) and employee creative deviance, enriching the theoretical research basis, foundation and relevant results of mediating variables (positive impression management motivation and harmonious innovation passion) and employee creative deviance, enhancing the applicability operability, feasibility of the moderating variables of employee growth need strength and professional mission sense of the relationships among mediating variables and employee creative deviance.This study fuses and integrates antecedent variable , mediating variables(positive impression management motivation and harmonious innovation passion), moderating variables  and outcome variable(creative deviance) into the same conceptual model and theoretical analysis framework, forms the moderation mediating function model, generates the moderation mediating effect, improves the moderation mediating effect function, derives and evolves the influence mechanism of playfulness personality on employee creative deviance with completeness, systematicness and commanding unity, demonstrates the function direction, function strength and significance level of mediating effects and mediating function under the moderating variables, and enriches the empirical research results of boundary conditions and situational factors of playfulness personality and creative deviance in the aspects of organizational personality trait, organizational psychology, organizational cognition and organizational behavior.This study empirically studies the influence mechanism of employee playfulness personality on employee creative deviance of employees, in order to explore the realization path of creative deviance. High-tech enterprises are facing with the resource allocation and distribution problems, and the limited enterprise resources cannot support the innovative ideas of all employees. However, innovation is an indispensable driving force for the rapid development of enterprise, therefore, creative deviance of employees can alleviate the contradictions between resource allocation and employee innovation to some extent, and help enterprises improve innovation performance. Managers should put emphasis on the attitude toward creative deviance behavior of employees, timely show their expectations for innovation results, appropriately recognize innovative ideas, design thinking and framework of employees, pay attention to the boundary conditions of professional mission sense and growth need strength of employees, identify the direction, intensity and mode of professional mission sense and growth need strength of employees, encourage employees to spend their time perfecting innovative ideas after their ideas are rejected. Meanwhile, managers should also pay attention to work motivation of employees, stimulate employee innovation passion, promote harmonious innovation passion and positive impression management motivation of employees, encourage employees to implement meaningful innovation behavior, promote employees to have clear understanding of creative deviance results, and provide long-term innovation power for creative deviance. In addition, when recruiting employees, managers should focus on the employees with playfulness personality traits, create playful, fun and vibrant atmosphere for the creative team. Managers cannot blindly reject and deny the innovative ideas, framework ideology, innovation approaches and channels, design thinking, carefully consider the feasibility and operability of innovative opinions, and continue to improve and optimize creative deviance behaviors and activities, so as to stimulate the innovation passion and work passion of the whole creative team.The sample is limited to the field of high-tech enterprises, which has some limitations. Further research should pay attention to the diversity of sample selection, select samples in different industries and departments, expand sample size and enhance sample diversity. In addition, this study only studies creative deviance from the individual level of employees, however, creative deviance is also affected by other levels such as leadership attitude and the overall atmosphere of creative team. In the further research, it is necessary to further adopt the cross-level analysis method to carry out empirical analysis of employee creative deviance.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.QL: data analyses and writing of the manuscript. ZZ: critical review of the manuscript. YL, YG, YH, and HW: formal analysis. All authors contributed to the article and approved the submitted version.This research was funded by Research Base of Science and Technology Innovation Think Tank of Liaoning Province , 2022 Economic and Social Development Research Project of Liaoning Province (20221s1qnwzzkt-011), 2019 Science Research Fund of Department of Education of Liaoning Province (JQW201915402), Humanities and Social Science Project of Shandong Province (2021-ZXCY-16), and Social Science Planning Project of Shandong Province (21CPYJ21).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.


The coronavirus disease (COVID-19) pandemic led to a catastrophic burden on the healthcare system and increased expenditures for the supporting medical infrastructure. It also had dramatic socioeconomic consequences. The purpose of this study is to identify the empirical patterns of healthcare expenditures’ influence on sustainable economic growth in the pandemic and pre-pandemic periods. Fulfilment of the research task involves the implementation of two empirical blocks: (1) development of a Sustainable Economic Growth Index based on public health, environmental, social, and economic indicators using principal component analysis, ranking, Fishburne approach, and additive convolution; (2) modelling the impact of different kinds of healthcare expenditures  on the index using panel data regression modelling (random-effects GLS regression). Regression results in the pre-pandemic period show that the growth of capital, government, and private healthcare expenditures positively influence sustainable economic growth. In 2020–2021, healthcare expenditures did not statistically significantly influence sustainable economic growth. Consequently, more stable conditions allowed capital healthcare expenditures to boost economic growth, while an excessive healthcare expenditure burden damaged economic stability during the COVID-19 pandemic. In the pre-pandemic period, public and private healthcare expenditures ensured sustainable economic growth; out-of-pocket healthcare expenditures dominantly contributed to the pandemic period. In 2022, a violation of national security, macroeconomic stability, and sustainable economic growth resulted from the spread of the COVID-19 pandemic and the emergence of new threats . In particular, according to the International Monetary Fund forecasts . The countries with a high level of Sustainable Economic Growth Index include Hungary, Moldova, and Estonia, while Ukraine, Bulgaria, Croatia, and Serbia are outsiders according to this indicator.According to the panel data regression analysis results (random-effects GLS regression) in 2000–2019, it is found that all types of healthcare expenditures have a statistically significant impact on the Sustainable Economic Growth Index. However, the growth of capital expenditures, domestic general government healthcare expenditure, and domestic private healthcare expenditure led to the growth of the Sustainable Economic Growth Index in the pre-pandemic period. These conclusions also correlate with the research results ,8,11, inOn the contrary, current healthcare expenditures and out-of-pocket expenditures negatively affect sustainable economic growth dynamics. It is interesting that in , while eIn turn, the panel data regression analysis results in 2020–2021 did not reveal a statistically significant impact of healthcare expenditures on sustainable economic growth during the COVID-19 pandemic. In turn, the modelling results showed a negative impact in the COVID-19 period of capital and current healthcare expenditures on the Sustainable Economic Growth Index. However, the impact of domestic general government healthcare expenditure and out-of-pocket expenditure on the sustainability of economic development is positive. Nonetheless, these results can be considered as reliable because the low quality of the model resulted from a lack of observations.It should be noted that all the above-described modelling results are fair only for the selected 15 European countries, but the methodology of the Sustainable Economic Growth Index’s construction and identification of the impact of healthcare expenditure on sustainable economic growth in pre-pandemic and pandemic periods might be applied to other geographic sample to obtain more complete results. The approach to development of the Sustainable Economic Growth Index might be applied to any country sample because it relies on public data (the World Bank Collections) and its construction is based on a step-by-step approach, which might be adapted to any country sample. Moreover, measurement indicators of sustainable economic growth were selected based on the literature review of differentiated publications, which makes its country-specific dependence relatively low.The generalisation of the theoretical block of this study regarding the identification of the relationship between healthcare expenditures and sustainable economic growth proves that scientific research in this direction is closely related to challenges and risks arising in the socioeconomic environment. This fact is confirmed by the results of the overlay visualisation built using the VOSviewer_1.6.17 toolkit . In partThe generalisation of the empirical block of this study allows us to conclude that in more stable socioeconomic conditions, ensuring the stability of economic growth implies an increase in capital healthcare expenditures. Capital health expenditures according to the World Bank methodology  “includeBoth the theoretical and empirical results obtained can be useful to scientists carrying out their research in this direction, to representatives of state authorities of the analysed 15 European countries in the context of policy reform in the field of healthcare and economic development strategy, as well as to the third-sector representatives, analytical companies, and international organisations, when creating explanatory and analytical notes.Although some interesting findings are obtained in this study, several limitations should be addressed. This study can be deepened by expanding the geographic sample and implementing separate blocks of regression modelling for different clusters of countries characterized by common economic growth rates. Moreover, as in ,6,7,8,9,


As an important part of the human intestinal microecology, the intestinal flora is involved in a number of physiological functions of the host. Several studies have shown that imbalance of intestinal flora and its regulation of the intestinal barrier, intestinal immune response, and intestinal flora metabolites (short-chain fatty acids and bile acids) can affect the development and regression of female reproductive disorders. Herbal medicine has unique advantages in the treatment of female reproductive disorders such as polycystic ovary syndrome, endometriosis and premature ovarian insufficiency, although its mechanism of action is still unclear. Therefore, based on the role of intestinal flora in the occurrence and development of female reproduction-related diseases, the progress of research on the diversity, structure and composition of intestinal flora and its metabolites regulated by botanical drugs, Chinese herbal formulas and active ingredients of Chinese herbal medicines is reviewed, with a view to providing reference for the research on the mechanism of action of Chinese herbal medicines in the treatment of female reproductive disorders and further development of new herbal medicines. The intestinal flora is a symbiotic microorganism colonized in the human intestine, which is an important component of the intestinal microecosystem and is also known as the “second genome” due to its large number, diversity and genetic information, and is involved in regulating metabolic, immune, endocrine and other physiological processes of the host . In receThe dialectical use of traditional Chinese medicine (TCM) to treat diseases has been practiced in China for thousands of years. Chinese herbal formulas are complex in composition and often consist of combinations of multiple botanical drugs, which are used to reduce toxicity and increase efficacy through complex concoction processes and interactions between botanical drugs . At the Therefore, this paper reviews the mechanism of action of herbal medicines in intervening female reproductive disorders from the perspective of intestinal flora, and introduces natural herbal medicines for treating female reproductive disorders, in order to provide a reference for clinical treatment and further research of herbal medicines for female reproductive disorders.14, which is about 10 times the total number of human cells  in the intestinal mucosa, thus promoting increased intestinal permeability and the release of endotoxins into the circulation, which bind to the corresponding receptors to conduct signals, leading to chronic inflammation, insulin resistance (IR) and hyperandrogenemia (HA), affecting immune and metabolic homeostasis  compared to control mice , glycolysis and mitochondrial oxidation. There is growing evidence that abnormal metabolism of BCAAs is closely associated with IR or metabolic disorders , and Preobserved . The metpatients . Signifipatients . Furtherpatients . The undvia enteroendocrine cells, intestinal chromophores and the immune system or directly through the intestinal mucosal barrier, and subsequently induce central responses by signaling via the vagus nerve or the humoral circulation  ratio and a decrease in the abundance of Ruminococcaceae, and the increase in F/B ratio was strongly associated with inflammation , reduced estrogen levels and FSH >25 U/L (2 tests >4 weeks apart) as the main diagnostic criteria, often associated with perimenopausal symptoms, low fertility or even infertility, and an increased risk of osteoporosis and cardiovascular disease affecting 1–2% of women’s reproductive health and quality of life . POI hasOI group . Thus, iß affects the diversity of the intestinal flora  and low density lipoprotein cholesterol (LDL-C) concentrations, increasing sex hormone-binding globulin (SHBG) and improving inflammation and oxidative stress, suggesting that probiotics can modulate inflammation in patients with PCOS . There aAtractylodes Macrocephala Koidz  could promote the proliferation of Bifidobacteria and Lactobacillus in the intestine of mice, reduce the number of harmful bacteria enterobacteria, improve the overall intestinal flora status, and maintain the intestinal microecological balance  Ohwi , could decrease glucose and improve IR by regulating intracellular insulin signaling, increasing cellular Ca-Mg-ATPase activity, and improving the transport of substances such as glucose and insulin in the body  and the extract of Panax ginseng C.A.Mey. were able to inhibit the number of ovarian cysts, elevated serum testosterone and E2 levels, inhibit the expression levels of macrophage infiltration, pro-inflammatory cytokines IL-1β, IL-6 and inducible nitric oxide synthase (NOS), inhibit NF-κB pathway, and improve PCOS through anti-inflammatory and antioxidant effects  is tanshinone, which has estrogen-like biological activity, increases serum LH and FSH levels, and inhibits the overexpression of T and P receptors. It was noted that the diversity index and species abundance of intestinal flora in the salvia miltiorrhiza cell-broken pieces group were significantly higher than those in the control group, and the number of Bifidobacteria and Lactobacillus also significantly increased , which in turn activates the brain nervous system and induces the pituitary gland to be sensitive to GnRH and increases LH secretion, and inhibits the release of inflammatory factors and improves ovarian function by anti-androgen synthesis but its mechanism of action needs to be verified by more studies.The main active ingredient of ncreased . This in related . It is hMany modern studies have shown that Chinese herbal formulas can improve the microecological environment of the intestinal tract and thus play a therapeutic role in a variety of female reproductive disorders .Bacteroides, (Eubacterium)_ventriosum_group and its differential fecal metabolites.  improved HA in PCOS patients by modulating the abundance of bolites. . Wang’s bolites. . The impreatment .Bifidobacterium and Lactobacillus increased and the relative abundance of Enterobacteriaceae decreased in PCOS patients, while the ovulation and cycle pregnancy rate increased and hormonal abnormalities significantly improved, suggesting that the control of PCOS phenotypes by CDD may be achieved by regulating the structure of the intestinal flora, promoting the growth of dominant bacteria such as Bifidobacterium and Lactobacillus in the intestinal flora, and inhibiting conditionally pathogenic bacteria such as Enterobacteriaceae  effectively increased the abundance of Lactobacillus and Bifidobacteria, improved intestinal barrier function, alleviated inflammatory response, and corrected disorders of glucose and lipid metabolism, and had therapeutic effects on obese PCOS patients , the proportion of eriaceae . This coeriaceae . In addirecovery . Anotherpatients . Hashi Bpatients .Akkermansia Blautia, Bacteroides, Butyricoccus and Coprococcus, decreased the F/B ratio and LPS-producing pathogens Proteobateria abundance, reduced pro-inflammatory factors, increased the expression of ocludin and claudin1, protected the intestinal barrier to reduce LPS transport, and inhibited TLR4/NF-κB signaling pathway to improve the inflammatory response in PCOS rats  reconstructed the structure of intestinal flora in PCOS rats, increased the abundance of COS rats , and theCOS rats . The decactivity . Treatment flora , and it UCG-008, Ruminococcaceae UCG-003 and Alloprevotella, to improve inflammation and correct IR  induced an increase in the alpha diversity of the intestinal flora of PCOS-IR rats, as evidenced by an increase in the relative abundance of Lachnospiraceae rrect IR . In anotrrect IR . In addid by EMs .Experimental studies have shown that many active ingredients in Chinese herbal medicines including alkaloids, flavonoids, triterpenoids, polyphenols and polysaccharides have the ability to improve the disorders of intestinal flora during reproductive disorders .Coptis chinensis Franch . Modern research has shown that berberine improves menstrual cycles, ovulation rates, endocrine abnormalities and metabolic dysregulation in PCOS. Berberine indirectly improved IR, regulated hormone secretion and increased ovulation and conception rates in PCOS patients mainly by reducing the relative abundance of polysaccharide flora, increasing the relative abundance of SCFAs producing flora and reducing endotoxemia . In addition, glycyrrhizin significantly inhibited LPS-induced levels of inflammatory mediators such as TNF-α, IL-1β, NO and PGE2 and attenuated the endometrial inflammatory response, making it a potential herb for the treatment of EMs , fruits (including grapes and peanuts) and red wine that maintains homeostasis of glucolipid metabolism, improves low-level inflammation and oxidative stress, and is beneficial in the treatment of metabolic, reproductive and inflammatory proliferative diseases  can effectively improve reproductive endocrine symptoms by regulating the diversity and composition of intestinal flora and its metabolites, SCFAs, indicating that the regulation of intestinal flora is one of the important channels for the treatment of reproductive endocrine diseases by Chinese herbal medicines. However, most current studies have only discussed the modulation of intestinal flora structure and composition, effects on intestinal immune inflammatory response and intestinal barrier function and on brain-gut axis by Chinese herbal medicines that improve reproductive function, while most studies on the mechanism of intestinal flora regulation by Chinese herbal medicines that alleviate reproductive dysfunction have only conducted association analysis studies, and further cause-effect studies are rare. Follow-up studies can be based on macro-genome sequencing technology to analyze the changes of intestinal flora structure under the intervention of Chinese herbal medicines in reproductive endocrine state, perform species function annotation, screen differential strains, and perform experimental validation by fecal transplantation or culture of specific flora based on specific flora regulated by Chinese herbal medicines that have been clearly identified in clinical and animal experiments to improve reproductive function. Then, correlation analysis was performed in combination with intestinal contents or fecal metabolomics, and validated by relevant pathway indicators, and the biological mechanisms of Chinese herbal medicines to improve reproductive endocrine function were explored in depth, with a view to elucidating the mechanism of action of Chinese herbal medicines in treating reproductive disorders.Bacteroidetes and genus Akkermansia, Bacteroides, Bifidobacterium, Prevotella, and Lactobacillus, while decreasing the abundance of phylum Firmicutes and F/B ratio, and prevent or treat female reproductive disorders through SCFAs, BAs, and LPS signaling. However, the role of intestinal flora on the active ingredients of Chinese herbal medicines to improve reproductive disorders has yet to be explored in depth. Therefore, the interaction between the active ingredients of Chinese herbal medicines as well as compounded active ingredients and intestinal flora deserves attention, and in vitro co-incubation of the identified active ingredients with the corresponding metabolic flora can be considered to further investigate the material basis of the effect of Chinese herbal medicines on improving reproductive disorders, in order to elaborate the material basis research of Chinese herbal medicines for treating reproductive disorders diseases and provide a basis for the research of new Chinese herbal medicines for improving reproductive functions.There are a wide variety of components in Chinese herbal medicines and formulas, and the material basis of the effect of correcting reproductive disorders is not clear. Based on the study of crude extracts, active ingredients and compounds of Chinese herbal medicines, the reproductive protection mechanism of their active parts or groups of active ingredients can be further investigated. Numerous studies have confirmed that Chinese herbal medicines can affect the growth and composition of microbiota, and can also be metabolically inactivated or transformed by microbiota, thus directly or indirectly affecting the therapeutic effects of drugs. Chinese herbal medicines regulate the structure of intestinal flora, increasing the abundance of phylum Akkermansia to regulate intestinal integrity and barrier function, and SCFA-producing bacteria to improve host metabolism and inflammation. Meanwhile, Chinese herbal medicines can reduce the abundance of pathogenic bacteria and inhibit LPS-induced metabolic endotoxemia and inflammation. Moreover, some Chinese herbal formulas can increase the levels of GLP-1 and PYY by stimulating enteroendocrine cells, thereby regulating the gut-brain axis and affecting glucolipid metabolism, for example, Wang’s YiJing Decoction. The above still needs to be verified by further studies in the future. Furthermore, there are still some shortcomings in the treatment of female reproductive disorders in Chinese herbal medicines. For example, there are different treatment strategies due to the different classification criteria of TCM for female reproductive system diseases, a single and small number of clinical study samples, and a lack of high-quality multicenter large sample studies. It is not clear which herbal components play key pharmacological roles in regulating intestinal flora, and there are significant limitations in the promotion and use of Chinese herbal medicines. Therefore, more high-quality clinical studies on Chinese herbal medicines for female reproductive disorders are needed in the future, so as to establish a quantitative system of TCM efficacy and promote safer and more effective use of Chinese herbal medicines. More importantly, the correlation between intestinal flora and disease-specific metabolites should be studied in depth, while finding the active ingredients of Chinese herbal medicines and screening out the specific ingredients that act on the relevant intestinal flora or metabolites, so as to finally achieve precise treatment for patients with female reproductive disorders.In this review, we explore the potential mechanisms by which Chinese herbal medicines are involved in improving female reproductive disorders and regulating the intestinal flora. Our review shows that Chinese herbal medicines increase the abundance of probiotic bacteria, such as


Osteoarthritis is the most common form of arthritis and is a substantial burden for patients with the disease. Currently, there is no cure for osteoarthritis, but many emerging therapies have been developed to aid in the mitigation of disease progression. When osteoarthritis reaches the end-stage of disease many patients undergo total joint arthroplasty to improve quality of life, yet some experience persistent pain and mobility limitations for extended periods following surgery. This review highlights recent therapeutic advancements in osteoarthritis treatment consisting of pharmacologics, nutraceuticals, biologics, and exercise while emphasizing the current state of post-arthroplasty rehabilitation. Osteoarthritis (OA) is a disease of high research priority as tens of millions of people in the US experience its deleterious impact on mobility and quality of life. The pathogenic process in OA is distinct from other musculoskeletal aging diseases such as osteoporosis , and conOA is the most common joint disease, characterized by the failure of the joint as an organ . Knee OAin vivo drivers of OA such as IL-1β to elicit a divergence in OA chondrocyte secretion of inflammatory mediators  relative to healthy cells  and intra-articular glucocorticoids are widely used to manage inflammation and pain, but they are best for short-term use  as long-Due to the lack of substantive benefit and risks of chronic opioid use in OA , nutraceRecent technological advancements have prompted new treatments for OA such as platelet rich plasma (PRP) –50, intrWith stem cell therapies there is vast diversity in the cell source and application method within the joint . This heAnother innovative treatment for patients with OA is the use of antibodies to block the pain signaling of NGF . NGF stiAs previously mentioned, a viable treatment option to mitigate OA progression is exercise , 10. ThiFor instance, water based exercise training is a common modality as it minimizes the weight bearing load upon the joint and can minimize pain ; howeverEnd-stage OA is often symptomatically described as a severe decline in the functionality of the affected joint , commonlTJA is a common procedure that provides many patients with relief from the moderate to severe symptoms of end-stage OA . UnfortuA wide range of rehabilitation approaches, perhaps best characterized as “usual care,” has yielded varying levels of efficacy post-TJA. However, many groups including our own hypothesize that progressive and intensive resistance training may be a key ingredient to optimize patient outcomes after joint replacement. When compared to usual care, progressive resistance training (PRT) improves functional measures such as leg press strength without increasing pain . FurtherOA remains a complex disease state that is not fully understood. However, remarkable strides have been made recently that aim to promote improved functionality and quality of life for those living with the disease. These advancements aim to potentially prevent or at least prolong the time before patients undergo more invasive procedures such as TJA. While TJA appears effective for many, little is known about why some patients continue to suffer from severe symptoms following the procedure, with even less known about how to optimally alleviate these problems. Exercise in particular appears to beneficial as a treatment for pain management and functional improvements with OA, and progressive resistance training may be necessary to optimally recover following TJA. However, many uncertainties persist within the field which limit the impact of exercise as an effective treatment or therapeutic option. To overcome this, comprehensive large-scale rehabilitation clinical trials are needed to better inform practitioners moving forward with rehabilitative care.DD co-conceptualized the manuscript, performed literature search, and wrote the manuscript. MB co-conceptualized the manuscript, edited the manuscript, and provided additional literature for inclusion. JM, RS, AF, SB, and JS edited the manuscript and provided additional literature for inclusion. All authors contributed to manuscript revision, read, and approved the submitted version.JS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JS is on the speaker's bureau of Simply Speaking. JS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 8 companies. JS serves on the FDA Arthritis Advisory Committee. JS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. The remaining 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.


The human gut is colonized by trillions of microorganisms that play a crucial role in maintaining the health , one flavonoid , DF and phenolic acid , and SCFAs  in maintaining gut health and preventing various health issues were explored.In this Research Topic, recent findings in the modulation of gut microbiota through DFs and bioactive compounds and their potential to promote gut health are pointed out. It comprised five papers, the role of two polysaccharides  Singer polysaccharides (LDSPs) on gut microbiota and their metabolites in the in vitro human fecal fermentation. LDSPs produced a significantly higher level of total SCFAs, particularly propionate and butyrate, compared to inulin, the positive control. The microbiota analysis revealed a distinct shift in the gut microbial composition between the LDSPs group and the inulin group. Notably, the LDSPs treatment increased the relative abundance of butyrogenic bacteria such as Blautia, Roseburia, and Faecalibacterium, and a positive correlation was found between butyrate production and these bacteria. The results suggested that LDSPs have the potential to demonstrate health benefits as a prebiotic.The study conducted by He et al. investigated the anti-obesity activity of a polysaccharide (TP) extract from Tremella fuciformis, a medicinal and edible fungus. TP supplementation could significantly reduce weight gain, fat accumulation, blood glucose, hyperlipidemia, and inflammation induced by the high-fat diet (HFD) in mice. This was achieved by regulating gut microbiota disturbance, improving gut barrier integrity, and increasing the production of SCFAs. The Firmicutes/Bacteroidetes ratio was reduced while the relative abundances of Muribaculaceae, Oscillospiraceae, Prevotellaceae, and Bacteroidaceae were increased with TP treatment. The anti-obesity effect of TP was also transferable through fecal microbiota transplantation, further confirming that the anti-obesity activity of TP was achieved via modulation of gut microbiota. Overall, the study suggests that TP is a promising prebiotic for the prevention and treatment of metabolic diseases such as hyperglycemia and obesity by targeting the gut microbiota.Meng et al., eriocitrin, a flavonoid present in lemon fruit, was applied to investigate its intestinal metabolic profile and effect on gut microbiota in mice. Eriocitrin and its six metabolites, including eriodictyol, homoeriodictyol, hesperetin, eriodictyol-3′-O-glucoside, hesperetin-7-O-glucoside, and eriodictyol-7-O- glucoside, were detected in the colon contents. The level of all SCFAs, particularly butyrate, valerate, and hexanoate, were significantly increased in the eriocitrin intervention diet group. This, in turn, was accompanied by an increase in the abundance of butyrogenic bacteria such as Lachnospiraceae_UCG-006. Moreover, Spearman's rank correlation analysis showed that Monoglobus, Faecalibacterium, Candidatus_Arthromitus, Lachnospiraceae_UCG-006, Gardnerella, and Lactobacillaceae_HT002 were positively correlated with the most of the eriocitrin metabolites, while Parasutterella and Muribaculaceae_unclassified exhibited negative correlations. These findings suggest that eriocitrin has the potential to positively impact gut health through the modulation of gut microbiota and metabolism.Besides DF, bioactive compounds such as polyphenols could also modulate gut microbiota and provide health benefits  on fermentability and capability to modulate gut microbiota was determined in vitro. Rice bran arabinoxylan (RAX), corn bran arabinoxylan (CAX), and their deferulyolated counterpart dRAX and dCAX, were subjected to an in vitro fecal fermentation model. The carbohydrate backbone and branches of AX played a more significant role in the fermentation pattern compared to feruloylation. Different Bacteriodes species were promoted by RAX and CAX, and the effect of feruloylation on butyrate production and alpha diversity varied depending on the carbohydrate structure. For instance, dRAX showed lower butyrate production, compared to RAX, while dCAX showed a higher butyrate production compared to CAX. This study highlights the importance of considering the combination of polyphenols and DFs in the modulation of gut microbiota.Furthermore, polyphenols were frequently either free or esterified bonded with DFs in foods, thus it is important to evaluate the mutual effect of polyphenols and DFs on the modulation of gut microbiota. In the study of Zhan et al., the potential role of SCFAs in controlling enteric pathogens is summarized. By extensively promoting the acylation of key bacterial proteins and regulating the gut barrier function and immune status, SCFAs could prevent the invasion of pathogens. It was noted that the types, composition ratio, and concentration of SCFAs greatly affected their regulatory role in the gut. The need for further studies to fully understand the role of SCFAs in controlling enteric pathogens is highlighted. The results indicated that increasing the production of SCFAs through dietary interventions or supplementation may be a promising approach for controlling enteric pathogens and improving gut health.SCFAs are the major metabolites of DFs in the colon and play a crucial role in the regulation of gut function (Koh et al., Overall, these papers provide important insights into the effects of various dietary components on gut health and highlight the potential of polysaccharides, flavonoids, and SCFAs as prebiotics. However, further research is needed to fully understand the mechanisms behind these effects and to determine the optimal composition and dosage of these compounds for optimal gut health. Additionally, future studies should also consider the role of individual differences, such as genetics and diet, in shaping the gut microbiome and its response to dietary interventions. Taken together, the papers contribute to the growing body of evidence supporting the importance of gut health and the need for further research into the gut microbiome and its role in health and disease.XZ drafted and wrote the manuscript. TF and YT reviewed and revised the manuscript. All authors contributed to the manuscript and approved the submitted version.


COVID-19 is placing an unprecedented strain on health systems in general, and healthcare delivery in particular . Health Telemedicine during and beyond COVID-19,” we highlight the consequences and changes in telemedicine caused by and following the pandemic. This includes not only the status of telemedicine in developed countries, but also discussions around its adoption across the geographical divide, specific gaps that apply to medical specialities such as pediatrics, and future areas of research and development, among others. The current pandemic affects diagnostic workup, medical treatment, and surgical procedures, as well as chronic management of diseases  during COVID-19. Authors identified infrastructure and regulatory barriers as the most significant barriers to telemedicine use in LMICs. The authors also concluded that telemedicine improved access to high-quality healthcare and mitigated infection risk during COVID-19.Lan et al. set out to investigate the research direction of telemedicine during COVID-19 by performing a bibliometric analysis to understand what type of telemedicine technology is employed in which diseases and what medical services are given by telemedicine. The study validated the wide use of telemedicine during COVID-19.Michel, Mettler et al. share their experiences with the COVID-19 online forward triage tool (OFTT) in pediatric settings in Switzerland. The authors concluded that it is essential that stakeholders, parents, teachers, and healthcare professionals participate in the development, setup, execution, and assessment of telehealth interventions as this can aid in managing expectations and increase the usefulness of OFTT. In another work, the authors explored attitudes, experiences, and challenges faced by OFTT users and their families, concerning public health recommendations . It appears that a wide range of interrelated elements affect how people feel about public health advice, which necessitates the use of systems thinking in public health communication. The authors also investigated the health care and health authority perspectives on the utility of OFTT during COVID-19 . The authors aimed to evaluate how this pandemic affected weight reduction via a very low-carbohydrate regimen that targeted nutritional ketosis administered via telemedicine (NKI). The OFTT's usefulness was found to be hindered by factors such as data privacy, doctor-patient relationships, resistance to change, regulatory and mandate concerns, and a lack of systems thinking.Kreider et al. provided an in-depth understanding of the therapeutic reasoning factors, supportive strategies, and practical solutions for telerehabilitation in Veterans. The quick transition of Veterans Health Administration (VHA) healthcare from outpatient rehabilitation services to telerehabilitation during the COVID-19 epidemic expedited gains in practical knowledge for implementing telerehabilitation, which is explained in this study.Another study by Athinarayanan et al. evaluated how COVID-19 affected weight reduction via a very low-carbohydrate regimen that targeted nutritional ketosis administered via telemedicine (NKI). Independent of pandemic stress and lifestyle restrictions, the authors found that a very low-carbohydrate telemedicine intervention produced comparable and clinically meaningful weight loss.Cheshmehzangi et al. call for an integrated approach from macro, meso, and micro levels to address these neglected barriers.In a commentary on the neglected digital divide barriers of telemedicine during COVID-19, The pandemics such as COVID-19 exacerbate health inequities and pressures on health systems and healthcare workers . Amidst Providing a framework, once health care gaps have been identified and the feasibility of delivery models understood, to health care governments and payors are critical to ensure ongoing real-time adoption of telemedicine platforms tailored to communities at greatest risk for adverse outcomes during and even after any health care crises. Outlining the provisions for telemedicine to such stakeholders also helps to ensure health care access for communities with the greatest health care disparities.The COVID-19 pandemic is causing an unprecedented public health crisis impacting healthcare systems, healthcare workers, and communities. The COVID-19 Pandemic Health System REsilience PROGRAM (REPROGRAM) consortium is formed to champion the safety of healthcare workers, policy development, and advocacy for global pandemic preparedness and action.SB conceptualized and wrote the first draft of the manuscript. SB, AN, MB, SM, and RW discussed the results and recommendations and contributed to the final manuscript. All authors contributed to the article and approved the submitted version.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.