Domestic violence (DV) is one of the major concerning health problems worldwide, and individuals who experienced domestic violence, may suffer physical or psychological consequences.Children as a major part of the family and society are usually involved in familial challenging events such as domestic violence, and suffer several major complications. This review aimed to explore the psychological consequences of child exposure to domestic violence. A systematic search in four databases yielded 18 peer-reviewed original studies that met the inclusion criteria. Selected studies highlighted the psychological consequences of domestic violence in witnessing and exposed children. The findings of the present study revealed that children exposed to DV suffer various psychological, mental, and behavioral complications which may be short and long-lasting, and moderate or severe. Children exposed to domestic violence may show declined educational performance and social abilities. Internalization problems, depression, post-traumatic stress disorders symptoms, and externalization symptoms such as aggressive behaviors and even lower levels of IQ are of most important reported complications of domestic violence in children. Educational programs for parents as well as trained school caregivers and health policy-makers can diminish and prevent the complications of domestic violence in children.Considering the importance of children mental hygiene, health policymakers should consider facilities to screen and detect children with signs of maltreatment and exposed to domestic violence. In this regard, trained teachers or school counselors will be helpful, as social supports and therapies may be more effective by early detection affairs. Domestic violence (DV) as a major worldwide health problem, has attracted the attention of social and health policymakers Finley . Family Medical subject headings were used to search related published studies in scientific databases including PubMed/MEDLINE, Thomson Reuters, Cochrane, and Google scholar. The search was conducted in the mentioned databases using Mesh keywords Domestic violence, Children (child), witness, exposed (Exposure), and psychological effects. Our search results included original research papers published in the English language from January 2000 until 2022, with their online abstracts. The study was conducted based on the inclusion criteria demonstrated in Table Data were extracted from the selected papers by two reviewers. Each article was evaluated separately and the results were merged. Discrepancies were resolved by referral back to the original papers. Extracted data included information about the authors of the studies, the year and country of the research, sample size, and the main findings of the studies. The results of the studies were merged in the discussion section considering other publications to respond to the questions: How do children suffer from domestic violence?Do children suffer DV physically or psychologically?What types of psychological disorders have children suffered because of domestic violence?Does DV affect social activity or educational performance of the children?Does DV affect Intelligence Quotient (IQ) or emotional intelligence (EQ) of the children?Do children express delayed consequences of DV?In our systematic review, the results were evaluated concerning the design and quality of the studies. The results of the studies were not combined due to the heterogeneity of the study types, populations, and outcomes. So, statistical analysis was not performed on the findings of selected studies.Totally, 2740 potentially relevant articles were found in the first-round search in the mentioned databases. By screening titles of found articles; 2225 titles did not meet the criteria to be included in the study and were excluded. Five hundred fifteen articles potentially fulfilled the inclusion criteria and went forward for screening for duplicates in Endnote Software version X7. In this stage, 150 records were removed and 365 articles were evaluated by two reviewers independently concerning inclusion criteria. The abstract of selected papers was reviewed and papers were selected considering the subject and inclusion criteria of the study. In this stage, 284 papers were excluded and 81 articles were evaluated for full-text screening. Finally, 63 articles were excluded by screening the full-text body of articles and 18 articles were selected for the final systematic review. In the present systematic review, we included articles evaluating the psychological impacts of domestic violence on children that were published from 2000 to 2020.Almost all studies indicated the negative impacts of domestic violence on children’s psychological status and their behavior. In the first study conducted by Levendosky and Bermann , 120 womHuth-Bocks et al.  evaluateIn another study, Levendosky et al.  evaluateChildren who witness DV may also suffer behavioral problems. For example, Spilsbury et al.  studied Fusco and Fantuzzo  evaluateRigterink et al.  also evaFortin et al.  conducteIn other studies, DV had led to negative and overwhelming emotions as well as suppression effect for young children Thornton  and reduLater in 2018, Cho , academic skills (or achievement), cognitive functions such as memory, focus and attention, and visual-motor coordination, neurocognitive tests, personality tests, and brain dominance. Considering the importance of children mental hygiene, health policymakers should consider facilities to detect children with signs of maltreatment and exposed to domestic violence. In this regard, trained teachers or school counselors will be helpful for screening and early detection of such children. So, social supports and therapies may be more effective by early detection affairs.


Several cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of its substrates, mainly the proteins known as STATs. STATs bind to these phosphorylated tyrosine residues and translocate from the cytoplasm to the nucleus, further regulating the transcription of several genes that regulate the inflammatory response. The JAK/STAT signaling pathway plays a critical role in the pathogenesis of inflammatory diseases. There is also increasing evidence indicating that the persistent activation of the JAK/STAT signaling pathway is related to several inflammatory bone (osteolytic) diseases. However, the specific mechanism remains to be clarified. JAK/STAT signaling pathway inhibitors have gained major scientific interest to explore their potential in the prevention of the destruction of mineralized tissues in osteolytic diseases. Here, our review highlights the importance of the JAK/STAT signaling pathway in inflammation-induced bone resorption and presents the results of clinical studies and experimental models of JAK inhibitors in osteolytic diseases. Bone architecture is one of the most important systems in the human body, supporting tissues and protecting vital organs . In addiBone constantly undergoes a process of resorption of older bones and the formation of new ones . This isOsteoblast and osteoclast activities are regulated by numerous cytokines expressed in the bone microenvironment . At the Therefore, this article reviews the role of the JAK/STAT signaling pathway during bone remodeling affected by inflammation and how its inhibition can be used as a therapeutic target in osteolytic disorders. To the best of our knowledge, this is the first review to gather results from clinical and preclinical studies on the use of JAK inhibitors in the treatment of inflammatory bone diseases.The JAK-STAT pathway was originally described as primarily activated in response to interferon (IFN)-gamma and members of the interleukin-6 (IL-6) family . It is nThe JAK family includes four tyrosine kinases  that are selectively associated with different chains of cytokine receptors for the phosphorylation of multiple protein-derived residues . The STACell activation through the JAK/STAT signaling pathway is very fast and effective after cytokines’ binding to their respective receptors . JAKs beA family of critical proteins in the transduction of signals and in the modulation of the JAK/STAT pathway are the suppressors of cytokine signaling (SOCS) proteins . The SOCHence, JAK/STAT signaling is crucial in initiating the innate immune response and orchestrating the mechanisms responsible for adaptive immunity . TherefoSeveral studies have shown that the JAK/STAT signaling pathway is closely related to diseases of autoimmune origin, probably through the intertwining of the immune and bone systems ,12,13,142, a cell hypoxia stimulant [Some studies have shown that the JAK2/STAT5B pathway plays an important role in the mechanisms of growth hormone activation, a regulator of bone growth and metabolism ,16,17. Ttimulant . Proteintimulant .In addition to the role of JAK in osteoblasts, research has demonstrated the crucial role of JAK in osteoclasts and, consequently, in bone resorption ,22. hMSCIn addition to the importance of JAK in bone cells, it is worth highlighting the role of cytokines that are also involved during the inflammatory process and their relationship with the JAK/STAT signaling pathway . StudiesThrough STAT6 phosphorylation, there is an inhibition of osteoclast activity by IL-4, and conversely, through phosphorylation of STAT5, IL-7 induces the formation of osteoclasts . IL-3, oFurther to the role of JAK on bone turnover under inflammatory conditions, it is important to highlight the relevance of the pathway for bone metabolism in physiological contexts. Genetically JAK1-deficient mice present less bone growth and lower body mass, fail to nurse despite the normal nurturing behavior of their mothers, and die perinatally . CorroboFinally, it is important to emphasize that not all JAKs and STATs are equally potent regulators of bone biology, which means that tuning the level of bone remodeling may be possible by acting on specific JAKs and/or STATs . FurtherDrugs that inhibit the JAK/STAT pathway to reduce signs and symptoms of inflammatory diseases have gained great interest. Some are already marketed and are increasingly subjected to research on their effects at different target sites . The del®), which aims to inhibit JAK1 and JAK2 in patients with myelofibrosis and polycythemia vera; Tofacitinib , which inhibits JAK1 and JAK3 in rheumatoid and psoriatic arthritis; and finally, Baricitinib, targeting JAK1 and JAK2, for the treatment of rheumatoid arthritis [The JAK inhibitors that are currently approved by the Food and Drug Administration(FDA) and the European Medicines Agency (EMA) are Ruxolitinib  ,53. ConsBy evaluating the use of the JAK inhibitor Tofacitinib in a rat adjuvant-induced arthritis (AIA) model, LaBranche et al. obtained satisfactory results, such as reduction of edema, inflammation, bone resorption, and plasmatic RANKL and IL-6 levels . In vitrIn rats with adjuvant-induced arthritis, tofacitinib markedly reduced the clinical status of treated rats compared to the control group . The maiSome recent studies provide valuable information about the efficacy and safety of different treatment options for rheumatoid arthritis and their impact on patient-reported outcomes (PROs) and disease progression ,59,60,61Overall, these studies highlight the importance of individualized treatment approaches for RA and the need to consider clinical and PRO factors when assessing treatment efficacy. Furthermore, the results suggest that newer treatments such as upadacitinib and tofacitinib may provide superior efficacy compared to traditional treatments such as methotrexate and adalimumab.A better understanding of JAK/STAT pathway activation for the occurrence and development of rheumatoid arthritis will allow the deepening of strategies and therapeutic targets and the development of JAK inhibitor antirheumatic drugs.Myelofibrosis is characterized by an overproduction of myeloid stem cells, bone marrow fibrosis, cytopenia, and extramedullary hematopoiesis, which exacerbates the release of inflammatory cytokines . Bone inA promising example is AZD1480, which blocks cell proliferation at low micromolar concentrations and induces apoptosis in myeloma cell lines via concomitant inhibition of the phosphorylation of signaling proteins JAK2, STAT3, and MAPK . In clinA problem associated with myelofibrosis is the appearance of infectious diseases . A reducSome recent studies have investigated different treatments for myelofibrosis, each targeting different disease pathways ,67,68. TOverall, these studies highlight the importance of targeted therapies in the treatment of myelofibrosis and suggest that different drugs may be appropriate for different patient populations, depending on individual disease characteristics.Further research using the JAK/STAT signaling pathway inhibitors should be carried out to define a protocol for clinical application in myelofibrosis.Periodontitis is one of the major causes of tooth loss in adults, affecting a high number of patients worldwide and creating a major public health concern that necessitates the discovery of novel therapies . PeriodoDuring periodontitis progression and chronification, numerous signaling pathways are activated depending on the nature of the causes . AlthougAnother study evaluated the effect of the absence of suppressor cytokine signaling protein 3 (SOCS-3) on inflammatory bone resorption in mice subjected to experimentally induced periodontitis. SOCS are a family of cell signaling molecules activated by microbial and immunological stimuli that downregulate cytokine signaling, inhibiting the JAK/STAT signal transduction pathway . The resIn contrast, JAK3 inhibition in mice with periodontal disease increased inflammatory infiltrate and bone resorption, indicating a protective role for JAK in the pathogenesis of periodontal diseases  Table 3Table 3. A clinical study comparing the periodontal status of patients with periodontitis and rheumatoid arthritis at baseline and 24 weeks after oral treatment with a JAK1-3 inhibitor indicated a reduction in periodontal inflammation . SimilarTill now, few studies have evaluated JAK/STAT signaling pathway inhibitors in periodontal disease. However, results suggest a promising role for this pathway in regulating the pathogenesis of periodontitis, and more studies are necessary to investigate further their clinical impact in patients . The adjOsteoporosis is of public health concern since it is a skeletal disorder characterized by compromised bone strength leading to an increased risk of fractures ,87, and JAK inhibition has shown promising results in the field of bone health. In an initial study , researcAnother successful case of using JAK/STAT pathway inhibitors was demonstrated in patients with Hutchinson-Gilford progeria syndrome (HGPS), an incurable condition that affects fetuses through premature aging, causing early death . ProgresAlthough there is limited research on the use of JAK inhibitors in the treatment of osteoporosis, these drugs have demonstrated potential in the treatment of the disease due to their ability to inhibit inflammation , increasIn recent years, a greater understanding of the signal transduction pathways involved in regulating cytokine production in immune cells has led to new discoveries in the development of therapies and treatments for various inflammatory diseases. One of these pathways, the JAK/STAT signaling pathway, has been the subject of numerous in vivo and in vitro studies due to its important role in the activity of several mediators relevant to the pathogenesis of osteolytic diseases.This review highlights new discoveries about how the JAK/STAT pathway is intimately linked to the pathogenesis of a number of osteolytic diseases that affect a large part of the world’s population. In addition, it summarizes how the inhibition of this pathway has become an attractive therapeutic target for the treatment of these disorders, highlighting the progress achieved so far and creating momentum for further research on the subject.Recent studies have provided evidence that inhibition of the JAK/STAT pathway can effectively reduce pro-inflammatory cytokine production and prevent bone destruction in several preclinical models of osteolytic diseases. These findings led to the development of several JAK/STAT inhibitors, some of which have already been approved for clinical use in the treatment of rheumatoid arthritis and other autoimmune diseases.Clinical studies in patients with osteolytic diseases have shown that the use of these drugs significantly reduces the symptoms of the disease, although they can increase the risk of secondary infections. In animals, JAK inhibitors have been shown to reduce the expression of inflammatory mediators, improving the signs and symptoms of inflammatory diseases such as rheumatoid arthritis and myelofibrosis. In vitro research also suggests that these drugs may reduce inflammation in bone cells and decrease the formation of bone-destroying cells, which may hold promise for treating these diseases. In periodontitis, although data from preclinical animal studies are conflicting, clinical studies have indicated improvement in periodontal parameters in patients using JAK inhibitors. Overall, these studies demonstrate the potential to target the JAK/STAT pathway as a promising therapeutic approach. However, it is important to conduct randomized controlled clinical trials to assess the safety and efficacy of these drugs, in humans, in addition to analyzing important aspects such as the duration of treatment, proper dosage, and possible side effects of these drugs in order to indicate protocols that are most suitable and efficient for the clinical use of JAK inhibitors in osteolytic diseases.


On one hand, the main difficulties in establishing a wide, evidence-based consensus about the best approach to visceral artery aneurysms (VAAs) and pseudoaneurysms (VAPAs) are the paucity of data, due to their rarity in the general population, and the extreme heterogeneity of this group of diseases, which encompasses different aneurysm types, with different degrees of rupture risks according to their anatomical locations .These two aspects cause uncertainty and debate when it comes to defining treatment indications, especially in asymptomatic VAAs, and therapeutic strategies; this is mirrored by poorly evidenced and sometimes inconsistent statements in the current guidelines. Here, we review how the current European and American Guidelines address the most controversial issues regarding VAAs and VAPAs, namely the treatment of asymptomatic VAAs, the surveillance protocol in case of conservative treatment or after endovascular repair, the choice of treatment for patients with ruptured and unruptured aneurysms and pseudoaneurysms (endovascular vs. open), and the need for parent artery preservation or reconstruction.The most recent European Society of Vascular and Endovascular Surgery (ESVS) Guidelines (last update in 2017) recommend the urgent treatment of patients with symptomatic VAAs and VAPAs  and the elective treatment regardless of the size of asymptomatic VAPAs, VAAs of the pancreaticoduodenal (PDA) and gastric duodenal artery (GDA) aneurysms, intrahepatic hepatic artery (HA) aneurysms, and women of child-bearing age with VAAs and recipients of liver transplantation  ).The 2020 Society of Vascular Surgery (SVS) Guidelines agree on the indication to treat all ruptured  and symptomatic VAAs and all VAPAs , but they were the first to introduce distinctions based on locations regarding asymptomatic VAAs . In factOther asymptomatic aneurysms should be surgically or endovascularly treated only if rapidly growing, or if their sizes exceed 2 cm for celiac trunk (CAAs), hepatic (HAAs), jejunal, and ileal aneurysms  and 3 cm for splenic artery aneurysms .This distinction is based on the estimated rupture risk, which depends not only on the aneurysm size or growth rate, but also on its site and location, an aspect which is noted in many retrospective studies, although with a high degree of heterogeneity . Moreover, unlike in the ESVS Guidelines, the indication for child-bearing aged women is expressed only for splenic artery aneurysms, whose ruptures during pregnancy with high fetal and maternal mortality are reported with a certain frequency .A conservative treatment with careful surveillance is recommended by both Guidelines for small asymptomatic aneurysms , with a A post-operative follow-up does not necessitate imaging after an open repair, whereas endovascular therapy (EVT), Computed Tomography Angiography CTA, , or MagnDistinctions made by the American Guidelines based on the aneurysm location generate more precise statements supported by higher levels of evidence . HoweverDespite the paucity of data, the two Guidelines share the view that endovascular treatment is burdened by lower perioperative mortality and morbidity rates, and so it should be preferred in anatomically suitable patients undergoing elective treatment. This recommendation is expressed as a general rule for all types of VAAs in the ESVS  and for each visceral artery in the SVS Guidelines, albeit with different levels of evidence. However, the most updated meta-analysis conducted by Barrionuevo et al. reported a significantly lower peri-operative mortality for endovascular surgery only for PDAA/GDAA and coeliac artery aneurysms, whereas the general mortality rates are not significantly different between open and endovascular surgeries .The therapeutic decision in the case of ruptured VAAs, especially in the case of hemodynamic instability, is even more controversial, mostly due to the rarity of studies and reports; moreover, most case series, systematic reviews, and meta-analysis do not distinguish their results based on ruptured/intact aneurysms, so peri-operative mortality and morbidity rates after the open vs. endovascular treatments of ruptured aneurysms are extremely difficult to estimate.The presence of hemodynamic instability and the need to evacuate an intraperitoneal hematoma often require emergent laparotomy and open aneurysm resection, with artery ligation or reconstruction . HoweverThe difficulty of comparing the outcomes of open and endovascular treatments is further increased by the wide variety of endovascular techniques, from embolization to the use of covered of flow-diverting (FD) stents, and their different applications . Among tThe choice must always consider not only anatomical suitability , but also the need to preserve the parent artery or the possible consequence of its intentional occlusion, and that is true in case of both EVT and open surgery (when choosing between artery ligation or reconstruction ,13. The Both Guidelines acknowledge the role of FDs as promising, but not yet fully elucidated, as well as the role of laparoscopic and robotic surgeries. The current literature provides the optimal results of these techniques, but the sample sizes are still too small to produce scientific evidence comparable to that of open or endovascular surgeries ,15.-The risk of the rupture of VAAs depending on their sizes, since the thresholds for elective treatment indicated by scientific societies are different;-The real risk of the rupture of small VAAs of the SMA and its branches in order to ascertain if they really deserve interventional treatment regardless of their size;-The best follow-up scheme for patients with intact VAAs at a low risk of rupture and the most suitable imaging technique for post-operative follow-up after endovascular treatment, especially coil embolization;-The most appropriate diagnostic and therapeutic work-up for ruptured VAAs and the criteria for choosing between open and endovascular surgeries;-The role of parent artery preservation in determining the decision between open and endovascular surgeries in both urgent and elective settings.In conclusion, based on the current scientific evidence, an integrated algorithm to guide decision making, including all treatment options for VAAs, cannot be constructed yet. Although the Guidelines agree on some basic aspects regarding the management of VAAs, many issues remain controversial, and they are based on scarce and low-quality data. Overall, the more recent SVS Document is more complete, but many questions are still unanswered and should be addressed by future investigations, including:These aspects could be clarified only by collecting and analyzing more data and comparing different experiences in clinical settings. Therefore, all vascular specialists experienced in the field are welcome to contribute.


Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the “DEPHENCE” system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the “DEPHENCE” system postulates. Ovarian cancer, especially its type II according to the dualistic model proposed by Kurman and Shih , represeOne of the main problems in the treatment of HGSOC is the existence of ovarian cancer stem cells (OCSCs) that reside inside tumor niches and cooperate with surrounding cells that compose tumor microenvironment (TME). The character of this cooperation shapes tumor behavior and influences several processes including dormancy, proliferation, metastasis, and, most of all, chemoresistance . Cancer The problem of the stemness is directly connected to the cancer dormancy that is dependent on the presence of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) that have partially overlapping functions and are enriched by the population of quiescent CSCs . CTCs, DOvarian CSCs are characterized by cell surface CD44, CD117, CD133, CD24, MyD88, epithelial cell adhesion molecule (EpCAM), leucine-rich repeat containing G protein–coupled receptor-5 (LGR5), and LGR6] and intracellular  markers, as well as by their specific behavior (“side-population” cells). The markers for characterization of OCSCs, their function, and clinical significance are presented in in vitro  and EMA (European Medicines Agency) using bevacizumab and poly-ADP-ribose polymerase (PARP) inhibitors. Several others drugs are being tested in clinical trials including programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors. HGSOC is initially a chemosensitive tumor, especially in the cases of positive Taking the abovementioned reflections into consideration, the interesting targets for multidirectional treatment are OCSCs themselves and the components of OCSC microenvironment, particularly metastatic niche. One of the most explored areas of anti-OCSCs therapy is drugs directed against OCSC markers, signaling pathways, and epigenetic regulators. Targeting OCSC markers is important as chemotherapy, whereas decreasing tumor burden simultaneously increases the number of OCSCs. After exposition to chemotherapy, increased numbers of ascitic EpCAM+, CD44+, and OCT4+ cells were noted . SimilarOne of the most important targets in TME is CAFs. However, the past experience with anti-CAFs therapy has indicated that the aim in this approach should be to revert CAFs functionally back to normal fibroblasts, rather than eradicating them completely from the TME. Eradication of CAFs has proved to change the tumor into more aggressive phenotype, instead of eliminating tumor cells . It is eThe next promising target for the therapy is metabolism of cancer cells. Cancer cells use both aerobic glycolysis (the Warburg effect) and oxidative phosphorylation (OXPHOS). Aerobic glycolysis protects cells from oxydative stress and fuels proliferation. However, OXPHOS and resistance to glucose deprivation in tumor environment are a metabolic adaptation enabling chemoresistance. Both ways of glucose metabolism are therefore used by cancer cells, including OCSCs and are another sign of their plasticity –368. TheAnother potential target for anti-TME therapy in HGSOC is exosomes. The identification of their origin inside TME and the recognition of their cargo have the key role in exosome-directed therapy. Exosomes could be also used as potential vehicles for the transportation of drugs into the tumor. It was also found that exosomes secreted from untreated tumors have a significant influence on the expression of many genes involved in functional change of fibroblasts into CAFs and in stimulation of tumor metastases. Such ability was less evident in exosomes secreted by pre-treated tumors . The sitThe urgent need for improvement of efficacy in the HGSOC treatment is obvious, and many researchers have called attention to the novel approaches in diagnosis, monitoring, and management of patients with ovarian cancer. We have learned from the experience from therapy of hematologic cancers and several solid tumors that the individual approach to the treatment based on genetic, molecular, or metabolic signatures of the patients and the cancer itself usually results in better treatment efficacy and improved outcome. However, such individualization of therapy is much more difficult to be used in solid tumors, compared to hematologic malignancies, and ovarian cancer due to its unique biology is even more demanding and challenging target.In the recent article devoted to OCSCs and OCSC-targeted treatment , we propavoidance of monotherapy, as usually combination of several drugs directed against different targets, is more efficient and, if properly orchestrated, could be less toxic;identification of the markers for pharmacologic compliance or resistance of the tumor and stratification of the patients according to the prognosis of treatment efficacy;performing the sampling of the tumor  repetitively for characterization of genetic signature and TME features, which could change in the course of the disease and in the response to the treatment;using the repeated biopsy of the tumor, but preferentially liquid biopsy, which enables to obtain more complex picture of growing tumor, as compared to standard biopsy the results of liquid biopsy do not depend on the site of the harvest of the sample;such approach and individualization of the therapy could enable to restore the pharmacologic surveillance over the tumor that fits the actual status of both tumor and the patient;every line of treatment should simultaneously target cancer cells, OCSCs, and elements of TME, as well as should generate potentialization of the patient’s immune status;HGSOC molecular types and different phases of the disease need different approach to the therapy;at the beginning, such therapy could allow for stabilization of the disease, hopefully enabling prolongation of PFS and OS; however, in a distant future the goal of this approach should be complete curation.We think that the necessary components incorporated into the DEPHENCE system should also beidentification of the high-risk population of women ;searching for the techniques of early detection or even for the screening tools both in the high-risk and general populations;searching for the infection factors responsible potentially for ovarian cancer origin ;looking for prognosis biomarkers of ovarian cancer.The practical implementation of the “DEPHENCE” system in the diagnosis and therapy of ovarian cancer is still awaiting, although the first signs of its use can be seen in the attempts to classify the molecular signatures of the tumors and TME components , 471–476TNF), estrogen receptor 1 (ESR1), mucin 1 (MUC1) genes, and hypermethylated downregulated forkhead box O1 (FOXO1) gene could serve as targets for epigenetic therapy and were correlated with patients’ prognosis , respectively. High-risk score tumors were positively correlated with abundant representation of checkpoint and immunosuppressive molecules, indicating the group of patients with compromised anti-tumor immune response . The DNArognosis .According to the TME components, the four different CAF subsets (S1 to S4) were identified in ovarian tumors. The HGSOC of mesenchymal subtype, defined by stromal gene signatures and poor survival, had high numbers of CAF-S1 cells, which attracted and sustained immunosuppressive infiltration of Treg CD25+FoxP3+ T lymphocytes . The stuBRCA1/2 genes (BRCA genes and in other homologous recombination repair (HR) genes were found to be responsible for secondary resistance to platinum- and PARPi–based therapy (The most painful problem in ovarian cancer therapy is the acquired chemoresistance following the initial good response to the first-line chemotherapy. Therefore, identification of the biomarkers of chemoresistance is one of the most important activities in ovarian cancer surveillance. The classic biomarkers of platinum and PARP chemosensitivity are the germinal and somatic mutations of /2 genes . However therapy , 489. On therapy . Four mi therapy . Treatme therapy . Hypoxia therapy . Hypoxic therapy . To over therapy 5. Simul therapy , 496. MoThe exploration of the infection factors in the origin or predisposition to ovarian cancer is also being realized in the analysis of microbiome and viral infections –499. AnoAll authors contributed to the conception of the review. Data collection and analysis were performed by JW, MW, and EP. The first version of manuscript was written by JW and MW, and all authors commented on previous versions of the paper. EP and MW read and approved the final version of the manuscript, made linguistic corrections, and revised the text. All authors contributed to the article and approved the submitted version.


The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism’s homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke. Stroke is a devastating cerebrovascular disease characterized by high morbidity, disability, recurrence, and mortality. The data provided by the Global Burden of Disease (GBD) 2019 suggested that stroke is the second most common reason for death and the third leading reason for disability across the world. Also, the absolute number of first-ever stroke and stroke-related deaths has increased considerably over the last decade . China hRecanalization and neuroprotection are the main approaches for treating IS in the clinic. Performing intravenous/intra-arterial thrombolysis and mechanical thrombectomy for effective reperfusion following recanalization are necessary for a positive prognosis of IS patients . The FooAlong with the typical neurological deficit in the acute phase , more thSeveral effective strategies have been proposed for treating disorders related to gut microbiota in IS patients. The gut microbiota can be modulated using two ways: (1) By identifying keystone taxa in the gut microbiome and performing interventions; (2) By altering the composition of the intestinal microbiota by single or combined use of dietary interventions, antibiotics, probiotics, fecal microbiota transplantation (FMT), or traditional Chinese medication (TCM). Several studies have also suggested that repairing the damaged intestinal mucosal barrier by gut-derived stem cell transplantation might be a new treatment strategy, which could prevent the occurrence of endotoxemia and secondary infections. Therefore, in this review, we discussed intestinal microbiota as an intervention technique for treating IS to gain further insights into the emerging field of IS therapy.via gut flora-related pathways is one possible mechanism  and metabolites (increase in propionate and butyrate), and further prevent neuronal cell death and memory dysfunction from the artery occlusion  is related to a lower risk of IS. The study also showed that drinking water enriched with calcium and magnesium, especially magnesium, can significantly reduce the risk of IS in postmenopausal women . Coffee The gut microbiota encodes many carbohydrate-active enzymes. Dietary fiber and carbohydrates in the diet can be fermented to produce short-chain fatty acids (SCFAs) through these enzyme systems. Many studies have shown that SCFAs can regulate immune responses, maintain gut barrier integrity, suppress the activity of histone deacetylases, and block the cascade of inflammatory reactions . Sodium Bifidobacterium was enriched , probiotics are live microbial food supplements or components of bacteria that are beneficial to humans when administered in adequate amounts . SeveralLactobacillus and Bifidobacterium are probiotics that can hinder the overgrowth of opportunistic pathogens and the invasion of foreign pathogens, and thus, help in maintaining the intestinal microecological balance, lowering the apoptosis of intestinal epithelial cells due to pathogens, protecting the intestinal mucosal barrier, and improving the intestinal and systemic immune functions , which aggravated microglia-induced neuroinflammation through the AKT/STAT3/NF-kB signaling pathway in the development of IS (Fecal microbiota transplantation is the most efficient intervention to reconstruct the gut microbiota and might be an effective therapeutic strategy for IS. A study found that FMT attenuated cerebral ischemic injury and improved neurological deficit in obese rats, which was probably mediated by the lowering of oxidative stress and apoptosis in the brain . FMT alsnt of IS . Additiont of IS , which iBifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum. The results showed that these SCFA-producing bacteria alleviated post-stroke neurological deficits and inflammation and increased the concentrations of SCFAs in the gut, brain, and plasma of aged mice after a stroke (As a key player in the MGBA, SCFAs can protect against neurodegenerative diseases by regulating the release of hormones and neurotransmitters mediated by G-protein-coupled receptors to further regulate inflammation and the mood of the patient . Among ta stroke . These fThese studies showed the beneficial effects of FMT on patients with neurological disorders. However, almost all studies were conducted on animal models. Additionally, one study conducted with an animal model for stroke also recorded an increase in mortality after FMT . As the Besides strategies directly modulating the intestinal microbiota, drugs that influence the intestinal microbiota might be more convenient in clinical practice. TCM emphasizes the holistic concept, which is consistent with the modern view of the MGBA in stroke. In China, since the Han Dynasty period, TCM practices have been passed down and evolved over thousands of years, and many classic and effective medicines have been developed for treating IS . Recent Traditional Chinese medicine can be used to effectively modulate intestinal homeostasis based on the concept of “homology of medicine and food” and the typical hepatoenteric characteristics of the pharmacokinetic profiles. Terpenoids, glycosides, flavonoids, steroids, polyphenols, and polysaccharides, among other bioactive substances found in TCM, can play distinct roles in multiple gut microbial metabolic pathways . These aHere, we briefly summarized the pharmacological effects of natural botanical active ingredients, TCM monomers, and compounds in the pathological state of IS based on the intestinal microbiota and their metabolites, as shown in The benefits of TCM for treating IS based on gut microbiota may be associated with reshaping the gut microenvironment, weakening of bacterial flora translocation, and an increase in probiotics to reduce cerebrovascular damage . To deveTuricibacter, isoflavones, phytoestrogen metabolites (Acupuncture treatment at different acupoints, such as Quchi and Zusanli , is an eabolites , and IPAabolites . AdditioSeveral studies have shown an association between a leaky gut and alterations in gut microbiota in patients with IS . The leaThe gut shows an early response to stroke, and changes in the gut occur simultaneously with stroke-induced hyperpermeability of the BBB. After the concept of MGBA was proposed, several studies showed the high clinical application value of the approaches targeting intestinal microbiota in the treatment of IS. The gut microbiota can influence the metabolic status of the body besides exerting strong effects on blood pressure, blood glucose, and atherosclerosis, all of which are risk factors for IS . A detaiQL and XL contributed to the conception and design of the study. JW wrote the first draft of the manuscript. JW, QL, and XL wrote sections of the manuscript. All authors contributed to the manuscript revision, read, and approved the submitted version.


Small towns play a crucial role in bridging urban and rural territory systems. While numerous studies have identified the characteristics and causes of small town shrinkage (STS), there remains an unexplored perspective on the reasons for their shrinkage from the perspective of the rural-urban relationship. To address this research gap, we investigated the relationship between STS and rural-urban interaction (RUI) in China. We hypothesized that a negative relationship existed between the degree of STS and the intensity of RUI. Using geo-statistical methods, such as the multi-scale geographical weighted regression (MGWR) model, the hypothesis was tested using Henan Province in China as a case study. The results indicated that the phenomenon of STS was observed extensively across the study region, with a 59% geographical overlap between the high-value area of STS and the low-value area of urban-rural interaction. Three distinct sub-types of STS regions were identified: shrinking regions along geographical borders, shrinking regions adjacent to metropolitan areas, and shrinking regions in ecologically fragile areas. The factors influencing STS demonstrated spatial heterogeneity and multi-scale characteristics. The findings will improve our understanding of urban shrinkage from a multi-level perspective and offer policy makers guidance for the sustainable development of small towns based on local conditions. However changes , 6. The  changes , particu changes , 9. Howe changes . Recedin changes . Our wor changes .China’s rapid urbanization has resulted in the concentration of resources, such as labor forces and land resources, from rural to urban areas. However, small towns in China have been unable to reap the benefits of urbanization due to a lack of skilled workers, limited financing channels, loss of labor force, insufficient infrastructure development, mono-industrial structure, weak management practices, and restricted jurisdiction , which hThe remainder of this paper is structured as follows. A concise review of the relevant literature is provided in the literature review section. Building upon prior research, the methodology applied and data used for the analysis are introduced in the section of materials and methods. The results section presents the obtained results, while a comprehensive discussion and conclusion are respectively presented in the discussion and conclusion sections.Xiangzhen in Chinese) are classified based on their administrative management unit, which corresponds to the fourth level of regional administration hierarchy: provincial administrative region, prefecture-level administrative region, county administrative region, and township administrative region from top to button. The spatial structure of small towns in China comprises two components: an urbanized area, similar to that found in developed countries, and an area covering a more rural population and agricultural land. Small towns in developed countries generally do not contain a significant rural population or areas of agricultural land, with the land being mainly urbanized areas [There is no universally agreed upon definition of what constitutes a small town . Traditied areas . This stth century. Over time, this dichotomy gave rise to two contrasting schools of thought. At one end of the spectrum was the anti-urban view which idealized and regretted the disappearance of rural life; at the other end was the pro-urban view which considered urbanization as the engine of progress, innovation, and modernization. The concept of urban-rural relationships has emerged as a way of challenging this longstanding and persistent dichotomy and promoting an integrated conception of cities and the countryside based on both their spatial and functional interdependencies. It was not until the 1960s, when the spatial linkages between urban and rural areas became a common concern that urban analysts shifted their focus from the city to encompass the broader city-region. In his vision for spatial development, Melvin Webber challenged the notion that “urban and rural areas represent a dichotomy that must be clearly manifested in the physical and spatial structure of cities, with orderliness contingent upon strict boundaries” [We have adopted the functional approach to define small towns, because of their key role in the urban-rural relationship, which has evolved from an urban-rural dichotomy to urban-rural integration. The acceleration in the historical urbanization rates and its associated social problems provide the context for the emergence of an urban-rural dichotomy that was particularly prominent during the late 19ndaries” . Over tindaries” . The linFrom the perspective of an urban and rural territorial system, small towns serve a dual purpose by functioning as both an extension and hinterland of cities, thereby representing the lower layer of the urban territory system. Conversely, they constitute the upper layer of the rural territory system, exercising jurisdiction over vast rural areas. Small towns possess significant functions that warrant their allocation. Firstly, the economic development of small towns plays a vital role in facilitating urban-rural interaction. Secondly, small towns serve as crucial hubs for farmers to exchange and distribute their agricultural products. As a transitional carrier bridging urban and rural areas, small towns exhibit remarkable sensitivity towards changes in urban-rural relationships. Their rise or decline serves as a concentrated manifestation of regional production flows and shifts in urbanization patterns . We haveAs an integral component of the urban regional system, it is crucial to comprehend the spatial contraction and driving mechanisms underlying small town shrinkage from a broader perspective. Typical symptoms of shrinking urban towns include population decline and economic downturn , 25. StuIn summary, previous research tends to categorize small towns as part of the urban territory system without acknowledging their crucial role as a “bridge” in RUI. It is imperative to recognize that small towns are not isolated entities. While some studies have acknowledged the bridging function of small towns in theory, empirical research has not sufficiently explored this function within the rural territory system. Additionally, it is of significance to develop the typology of STS to interpret the development paths of the large number and diverse types of small towns. From the functional perspective, small towns serve as both bases for diffusing urban civilization and centers for organizing the development of rural territories . HoweverIs there a negative correlation between the degree of STS and the intensity of RUI, and how is this relationship manifested geographically?If such a negative correlation exists, what are the primary factors contributing to STS? Are there regional variations in the factors affecting the shrinkage?Henan Province, located in central China, is recognized as a traditional agricultural province , possessThe RUI evaluation index system is a comprehensive system consisting of a set of interrelated and independent index factors that can be measured quantitatively . It enco2 or more. The research data were obtained from the China Statistical Yearbook (Volume of Township) from 2016 to 2021. Various definitions have been employed to delineate urban shrinkage, although they commonly highlight population decline as the primary symptom . There aThe entropy weight TOPSIS method represents an enhancement of the conventional TOPSIS evaluation approach. In this method, the weight of the evaluation indices are determined through the entropy weight method, and then the TOPSIS method uses technology to approximate the ideal solution. The entropy weight method is used to objectively determine the weight according to the information provided by each evaluation index. Because the entropy is a weighted number, it can objectively reflect the importance of an index in the index system when making decisions. The details of the operation are presented in Martin et al. .Different spatial, economic, social, and subjectivity functions may have various urban-rural connections which may result in a spatial effect on STS at changeable scales, which means spatial heterogeneity and homogeneity may coexist. In this study, an ordinary least squares (OLS) regression was first applied as a preliminary test of the correlation between STS and explanatory variables and the key results were selected for further analysis by GWR and MGWR , 40.1. The OLS regression. The traditional hedonic model could be expressed as an OLS regression, which means for each observation of STS yi:β0 is the intercept, xi represents the independent variable, βi is the corresponding coefficient, and ε is the error.2. The GWR. Compared to the OLS regression model, the GWR model strengthened the expression of spatial heterogeneity by adding space-varying parameters according to the coordinates of each observation . The GWR equation for STS yi could be written as:β0 and βk are the intercept and the coefficient of local variable k at location i, respectively, and xik is the k variable at location i.A GWR using a single bandwidth is not capable of expressing such features, while an MGWR could overcome these problems by assigning specific bandwidths for each variable based on an iteration. The MGWR could be written as:The OLS, GWR, and MGWR models could be applied directly via the MGWR software .i values of the degree of STS and its subsystems , and the number of industrial enterprises with an annual main business income of 20 million yuan or more showed negative growth in 630 small towns . However, only 215 small towns  experienced a decline in the number of general stores or supermarkets, which play a crucial role in facilitating daily living functions. daily living functions. The entropy weight TOPSIS method was employed to calculate the degree of STS in Henan Province. The results were then visualized using the ArcGIS Pro platform after conducting a kernel density estimation (KDE) based on the Cbsystems .The results indicated that the characteristics of STS could be attributed to geographical marginality, with areas exhibiting a higher degree of shrinking primarily located in the inter-provincial border regions, especially along the mountainous areas from northwest to south in Henan Province, including the Taihang, Fu Niu, and Dabie mountains. Another significant shrinking region was identified adjacent to the metropolitan area, specifically Zhengzhou City, the capital of Henan Province. This phenomenon was attributed to the siphon effect of the metropolitan area on the surrounding towns, resulting in the migration of population and economic elements towards the core city. Consequently, the spatial pattern of the small towns adjacent to Zhengzhou City displayed moderate shrinkage. Finally, typical shrinking regions were also found in ecologically fragile areas, such as the Yellow River beach area that extends from Baihe, Mengjin County, Luoyang City to Zhangzhuang, Taizian County, and Puyang City. The beach area has long been associated with poor living and production conditions, as well as relatively weak economic development, and certain areas are considered key poverty zones in both Henan Province and China overall. In summary, the study identified three sub-types of STS regions, namely the shrinking region along the geographical border, the shrinking region adjacent to the metropolitan areas, and the shrinking region in ecologically fragile areas .i values, which were then classified into five categories based on the natural breakpoints classification (NBC) method. The spatial pattern of RUI intensity is presented in 19), which reflects the functional identification of the rural system, had a weight coefficient of 19.09%; the urbanization rate (X1), which reflects spatial agglomeration, had a weight coefficient of 15.79%; and the proportion of employees in non-agricultural industry, which reflects educational services, had a weight coefficient of 14.16%.To measure the intensity of RUI in Henan province, we used the entropy-weighted TOPSIS method to obtain C2) of the total area, and the second level, i.e., the orange-covered regions in the map, accounted for 30%  of the total area. The summed percentage was 59% , which means there was a 59% geographical overlap between the high-value-degree of STS and low-value-intensity of RUI.To explore the spatial connection between the intensity of RUI and the degree of STS, the overlay analysis tool was used to intersect Figs Ci values of STS in each county were taken as the dependent variable (Y), while the factors influencing the intensity of RUI were taken as the independent variables (X); Subsequently, OLS, GWR, and MGWR were calculated based on Eqs 2 values from the OLS, GWR, and MGWR were 0.995, 0.995, and 0.998, respectively indicating fitting degree of 99.8% for the MGWR model. This confirms that the mechanism governing spatial heterogeneity in STS can be effectively verified using the MGWR model.The spatial heterogeneity of the relationship between the degree of STS and intensity of RUI was investigated at the county scale. Firstly, the mean During the application of MGWR, both the GWR and MGWR results were generated by the MGWR software with the interval bandwidth searching method . The res1, X4, X6, X8, X10, X11, X12, X16, X18, and X19 exhibited a global scale, while the remaining variables demonstrated a local scale effect. This suggests minimal spatial heterogeneity and indicates that the influence of these aforementioned variables on STS is consistent across all regions. Concerning the global variables, with the exception of X18 which showed no significant impact on STS; all others had a negative impact. In terms of the local variables, except for X9 and X17 which did not exhibit any significant impact on STS; all other variables had a negative impact.Compared to the bandwidth value of 157 displayed by the GWR model, MGWR assumed that the bandwidth ranged from 44 to 156 . The resThe MGWR results revealed spatially varying scale characteristics of all variable coefficients, accompanied by the acquisition of their statistical p-values, thereby providing more precise insights into the co-occurrence of spatial heterogeneity. Notably, the marginal mountainous areas at a global scale exhibited significant influence from the intensity of RUI on STS . SpecifiThe three indicators in the RUSP dimension exhibited a negative correlation, indicating that higher intensity of RUSP was associated with lower degrees of STS, which aligns with the hypothesis of this study. Furthermore, there existed spatial heterogeneity, with transportation convenience displaying localized characteristics. Specifically, the shrinking region along the geographical border was primarily influenced by the rural-urban information degree, the shrinking region in the ecologically fragile area was mainly influenced by the two factors of rural-urban spatial agglomeration and transportation convenience, and the shrinking region adjacent to the metropolitan area was predominantly influenced by the rural-urban transportation convenience. Notably, due to its localized nature, rural-urban transportation convenience had a significant local explanatory effect on both ecologically fragile areas and the region adjacent to the metropolitan area .The underlying reasons contributing to this phenomenon can be summarized as follows. 1. Efficient transportation infrastructure facilitates seamless mobility between urban and rural areas, fosters the flow of goods and services, attracts increased business activities and investments, and enables enhanced economic exchanges between small towns and the external world. Moreover, it contributes to more optimal resource allocation encompassing healthcare, education, and other social services while augmenting the allure of small towns, all of which could mitigate the issue of population decline in small towns. 2. Robust information connectivity enables small towns to swiftly access valuable information and knowledge, thereby facilitating local enterprises and residents in seizing novel business opportunities and fostering development. Moreover, it promotes the dissemination and application of technology, enhances social and cultural exchanges, as well as facilitates garnering attention and support from governmental bodies and other organizations. This holds immense significance in augmenting production efficiency and competitiveness within small towns.The five indicators in the RUET dimension exhibited a negative correlation, indicating that as the intensity of RUET increased, the degree of STS decreased., which was basically consistent with the hypothesis of this study. The five indicators reflecting the RUET displayed different spatial heterogeneity characteristics. In the case of the three sub-types of STS, the shrinking region along the geographical border was mainly influenced by the factors of economic aggregation, employment structure, and the income gap. Meanwhile, income gap played a dominant role in shaping shrinkage patterns in ecologically fragile regions, whereas the industrial structure and income gap were identified as key factors influencing the shrinking region adjacent to the metropolitan area. Given that the industrial structure and economic aggregation have local effects, it was suggested that these factors significantly contribute to explaining the dynamics of STS in the shrinking regions along the geographical border and adjacent to the metropolitan area .The underlying reasons contributing to this phenomenon can be summarized as follows. 1. The increasing market opportunities are attributed to the strong economic ties between urban and rural areas, facilitating small towns’ access to urban markets, expanding sales prospects for local businesses, and fostering economic growth. 2. Resource sharing is facilitated by robust urban economic links in rural areas, enabling the exchange of resources such as human capital, technology, equipment, and capital. This collaboration enhances productivity in small towns while reducing production costs. 3. Strong urban-rural economic links facilitate labor mobility between cities and villages, attracting new residents and workers to small towns and mitigating population decline. 4. The substantial economic connection between urban and rural areas contributes to the diversified economic structure of small towns beyond reliance on agriculture or traditional industries. Consequently, these towns become more resilient to risks and better equipped to adapt to changing economic conditions. 5. Innovation and technology transfer are fostered through the interdependence of cities as centers of innovation and technological development with their rural counterparts. This symbiotic relationship promotes knowledge dissemination and technological advancements benefiting small towns’ competitiveness.Among the seven indicators in the RUSI dimension, the number of health care service staff reflecting the factor of medical service; the number of urban and rural residents enjoying minimum living allowances reflected the degree of living allowances, the per capita household consumption ratio, and the urban and rural Engel coefficient; and all these factors exhibit a negative correlation. For three sub-types of STS, the shrinking region along the geographical border was mainly affected by educational services, medical services and living allowances primarily impact the shrinking region in ecologically fragile areas, while educational services and medical services. have a major influence on the shrinking region adjacent to the metropolitan area. Educational services, medical services, and living allowances had a global effect, which indicated that all three factors had a strong effect on STS across the region. It was further observed that the population shrinkage of small towns was a unidirectional process of life-oriented movement under urbanization .The underlying reasons contributing to this phenomenon can be summarized as follows. 1. Enhanced social stability and reduced contradictions and conflicts can be achieved through strong social connections between urban and rural areas, thereby making small towns a more appealing residential option for attracting and retaining residents. 2. Strong social links between urban and rural areas facilitate cultural diversity, social vitality, and effective communication, thus enhancing the attractiveness of small towns. 3. The availability of robust social support systems such as friendship networks, family ties, and comprehensive social services can significantly improve the quality of life in small towns, fostering livability. 4. Governmental support along with contributions from nonprofit organizations often reinforce the strong urban-rural ties by directing additional resources towards infrastructure development, education provision, medical services enhancement in small towns.All factors, except for the level of agricultural mechanization in the RUFI dimension, exhibited a global impact with positive correlations among all indicators. Specifically, a stronger urban function was associated with higher STS, aligning with the current reality of rapid urbanization in China. In terms of functional identification within the rural system index layer, the indicator of the agricultural mechanization level demonstrated a negative correlation, with their main influencing regions being in the shrinking region along the geographical border. Here, the RUI in the context of integrated rural-urban development did not exhibit an urban bias, where cities dominated over rural areas or an equilibrium-oriented approach that disregards differentiation between urban and rural functions. Instead, it fostered interactive development while preserving individual characteristics of the urban and the rural, while preserving individual characteristics of both urban and rural domains to collectively promote regional progress. Therefore, the premise of integrated urban-rural development is based on a high degree of urbanization, industrialization, agricultural modernization and informatization, the ideal state of which should be the preservation and continuation of the significant functions for the rural region. The negative correlation between the index layer of the functional identification of the rural system and the STS also validates our hypothesis .The underlying reasons contributing to this phenomenon can be summarized as follows. 1. The development of urban centralization entails the reinforcement of urban and rural main functions, which may result in resource and opportunity concentration in major cities or urban centers, thereby attracting a larger population and increased investment while diminishing the appeal of small towns. Major cities often offer more employment opportunities, educational facilities, medical resources, etc., which allure residents from smaller towns. 2. The outflow of rural population is an outcome of strengthening urban and rural main functions as rural inhabitants are inclined to migrate towards cities in search for improved employment prospects and living conditions, which further undermines the demographic foundation of small towns. 3. There exists an uneven distribution of resources due to the bolstering of urban and rural main functions. This occasionally leads to imbalanced resource allocation with cities receiving greater government support and investment compared to insufficient development in terms of infrastructure and public services within small towns; consequently, affecting their attractiveness. 4. There is pressure associated with urbanization and modernization accompanying the enhancement of urban and rural main functions that can potentially alter people’s lifestyles and values while gradually eroding traditional culture as well as social structures within small towns.China has a rich history of agrarian civilization, spanning vast territories. Small towns have long served as the economic, cultural, and social centers of rural areas, especially in the rural hinterland. China is currently experiencing rapid urbanization, characterized by a unidirectional flow from rural to urban areas. In light of this context, we put forward a hypothesis suggesting a negative relationship between the intensity of RUI and the degree of STS. Specifically, higher RUI intensity is expected to be associated with lower STS degree, and vice versa. To examine this hypothesis, we selected Henan Province in China as our case study.In terms of their spatial pattern, a negative correlation was observed between the degree of STS and the intensity of RUI. High-value regions of STS were found to spatially coincide with low-value regions of RUI. The spatial overlay technique revealed a 59% spatial overlap between the high-value regions of STS and low-value regions of RUI as determined by the NBC method. Furthermore, our hypothesis was confirmed by the results of the MGWR analysis. 13 of the 19 evaluation indicators in the RUI system exhibited a negative correlation in the explanation of STS. It is worth noting that our study only considered shrinkage as an explanatory factor for small town development, however if growth was also considered, there would be a stronger explanatory effect on the relationship between small town development and urban-rural interaction. The extent of STS can be classified based on the surrounding geographical conditions leading to identification of three sub-type regions: the shrinking region along the geographical border, shrinking region adjacent to the metropolitan area, and the shrinking region in ecologically fragile areas.The factors influencing STS effectively captured the characteristics of geographical scale and spatial heterogeneity. Whether in a rural-urban territory system or an urban territory system, the STS mechanism is intricate due to the unique functions of small towns. Our work significantly contributes to this research field by expressing the spatial heterogeneity from the perspective of RUI. Among the negatively correlated indicators, there are local indicators, such as rural-urban transport convenience, income gap, employment structure, and education services. The shrinking region along the geographical border is mainly influenced by factors, such as the rural-urban income gap, employment structure, and education services. The shrinking region adjacent to the metropolitan area is predominantly influenced by the factors of rural-urban transport convenience and educational services, and the shrinking region in ecologically fragile areas was mainly influenced by rural-urban transport convenience and the income gap. To convey the these perspectives directly, we have created a schematic diagram .Theoretically, STS exhibits a scale effect, which necessitates further investigation within the context of small towns maintaining their pivotal role in expanding economic networks or transforming human settlement systems. Small town shrinkage is the result of globalization, regionalization, and localization at multiple scales with varying degrees of influencing factors . For exaBased on the aforementioned discussion, we contend that future research could focus on the following aspects. Firstly, to enhance our comprehensive understanding of STS, forthcoming studies ought to delve deeper into cross-scale issues. This necessitates examining how factors at varying scales, ranging from local to global, interact and influence STS dynamics. Comprehending these interrelationships across different scales is pivotal for formulating effective policy interventions. Secondly, future investigations will place greater emphasis on the localized spatial effects of STS. This encompasses scrutinizing how factors such as land use, infrastructure development, and community characteristics impact the expansion or shrinkage of small towns. The local context plays a significant role in comprehending STS phenomena. Thirdly, comparative studies encompassing diverse regions can yield valuable insights into the drivers and consequences of STS. Such studies can aid in identifying best practices and lessons that can be applied in various contexts. Fourthly, research should continue to underscore policy implications by identifying effective policies capable of mitigating the adverse impacts of STS while promoting sustainable development in small towns; policymakers require evidence-based recommendations to address this issue.This study analyzed the degree, spatial association, and spatial heterogeneity of STS from 2015 to 2020 in Henan Province of China, by using the MGWR method to conduct empirical research on the factors influencing STS at the county level from the perspective of RUI. The study found that: firstly, there is a negative relationship between RUI and STS. The results showed that there was a 59% spatial overlap between the high-value regions of STS and low-value regions of RUI, which means the viewpoint was explicated in 59% of cases indicating a significant proportion of instances where the findings were elucidated. Secondly, the 59% overlap regions can be categorized into three geographical types, namely the shrinking region along the geographical border, shrinking region adjacent to the metropolitan area, and the shrinking region in ecologically fragile areas, which is also considered as the sub-types of STS. Thirdly, the characteristics of geographical scale and spatial heterogeneity were represented in the factors influencing STS from the perspective of RUI. The findings revealed spatial heterogeneity in the influencing factors across the three geographical types of STS. For instance, the STS in region adjacent to the metropolitan area is primarily driven by disparities in urban-rural income and the main function of the urban system.The findings have contributed to a more comprehensive understanding of the formation process and mechanism of STS, thereby providing a solid foundation for formulating sustainable and holistic development policies for small towns. It is important to the type and level of support required by small towns will vary depending on their location. For instance, small towns in peripheral regions necessitate different types/levels of support compared to those located in thriving metropolitan regions. Taking the shrinking region along the geographical border in Henan Province as an example, it predominantly encompasses mountainous areas, such as Dabie, Fu Niu and Taihang mountains. These regions are characterized by high population mobility, deep poverty, and inter-provincial borders, and serve as an important ecological security barrier. Consequently, considering the diverse geographical and ecological characteristic of small towns, there should be a focus on enhancing infrastructure facilities while establishing leading industries with substantial driving effects. In summary, addressing STS-related challenges should adhere to the fundamental principles such as adapting to local conditions and promoting classification in order to effectively implement appropriate strategies based on scientific evidence.S1 File(XLSX)Click here for additional data file.S2 File(XLSX)Click here for additional data file.


Electronic, optoelectronic, and optical devices have become integral to the fabric of the modern life, underpinning critical advancements in information technology, energy utilization, biotechnology, environmental monitoring, and nanotechnology. In the relentless pursuit of superior device performance, an imperative task emerges—the exploration of fresh frontiers in optical and electronic material properties, with a focus on their applicability within these devices. Within this context, nanocrystals and nanostructures emerge as compelling candidates, seamlessly integrated into devices while endowing them with unique physical properties, distinct from their bulk counterparts.We present to you this Special Issue of Nanomaterials dedicated to exploring the remarkable advancements in the realm of photonic and electronic materials based on nanocrystals and nanostructures. This compilation of cutting-edge research and review articles explores innovative methods for enhancing nano-scale materials in the realms of energy storage, power generation, mechanical properties, stability, and optical sensing.6 nanoparticles [2+ and Sn4+ ions, resulting in hexahydroxide nanoparticles with enhanced energy storage capabilities. The insights gained from this study offer a promising avenue for the development of next-generation energy storage applications.The pursuit of efficient energy storage solutions has never been more critical, and in our first article, Velmurugan et al. delve into the realm of Ni and Sn perovskite NiSn(OH)articles . ThroughTriboelectric nanogenerators (TENGs) offer a unique approach to harvesting mechanical energy, and the work of Kim et al. takes this concept further by incorporating an intermediary layer of gallium-based liquid metal particles . Their iMechanical properties play a pivotal role in performance of materials, and Lee et al. explore the influence of mucin on the mechanical properties of vesicles . Their a3 perovskites while addressing challenges posed by environmental factors, offering valuable guidance for researchers seeking to harness the full potential of perovskite nanomaterials.Perovskite nanocrystals have captivated researchers for their optoelectronic properties, and Liu and Lee provide a comprehensive review of advancements in perovskite nanocrystal stability enhancement . The autLastly, Rajamanikandan et al. present a detailed review on the optical sensing of toxic cyanide anions using noble metal nanomaterials . This woThe collective contributions in this Special Issue represent a significant stride in advancing the field of nanomaterials and their applications. We extend our heartfelt gratitude to the authors for their exceptional research and to the peer reviewers for their valuable insights that have enriched the quality of these articles. We hope that this compilation sparks new ideas, encourages collaborations, and inspires further investigations into the vast potential of nanocrystals and nanostructures in the realm of photonic and electronic materials. As we journey through these pages, let us be reminded of the transformative power of nanotechnology in shaping the future of science and engineering.


The paper proposes an enhanced design for broadband digital receivers that aims to improve signal capture probability, real-time performance, and the hardware development cycle. To overcome the issue of false signals in the blind zone channelization structure, this paper introduces an improved joint-decision channelization structure that reduces channel ambiguity during signal reception. Xilinx’s high-level synthesis (HLS) tools are used for accelerated algorithm implementation, and techniques such as pipelining and loop parallelization are employed to reduce system latency. The entire system is implemented on FPGA. The simulation results demonstrate that the proposed solution effectively eliminates channel ambiguity, improves algorithm implementation speed, and meets the design requirements. Since the beginning of the 21st century, with the rapid development of modern electronic technology, electronic information warfare has become a major form of warfare between nations. In electronic warfare equipment, more and more advanced technologies are being applied in the fields of jamming, anti-jamming, reconnaissance, and counter-reconnaissance, making the electromagnetic environment increasingly complex ,4,5.Traditional electronic warfare receivers mostly use analog technology design, including crystal video receivers, compression receivers, superheterodyne receivers, Bragg receivers, instantaneous frequency measurement (IFM) receivers , and chaDue to the limitations of analog devices, traditional receivers have a good performance but are heavy and bulky, with poor flexibility . With thThe ability to achieve full probability reception of signals across the entire frequency band is the most important performance metric for wideband digital receivers. A simple and effective method is to construct an overlapped digital channelization model, where the channel parts overlap and the processed signals are seamlessly joined in the frequency domain ,12. AlthThe limited application of broadband digital receivers is partially due to the mismatch between the speed of hardware development and theoretical development. With the rapid development of integrated circuit technology, digital receivers based on field-programmable gate arrays (FPGAs) have a good performance and can meet practical needs . FPGAs hIn the hardware implementation of the digital channelization receiver, if the traditional FPGA development process is used, the debugging and development cycle of the entire system will also increase when the data volume is large. Refs. ,18 have This paper presents an improved method to address the issues of false signals in digital receivers. The proposed method transforms the process of eliminating false signals into extracting amplitude-frequency information from the output signals. This not only improves the discrimination of useful signals, but also simplifies the implementation process of FPGAs. Additionally, the paper employs a hybrid design approach by combining the HLS design approach  with traK subbands by K filters. After D-fold decimation, the output results are obtained, and this process satisfies:For the digital channelization filter bank, the input signal s(n) is down-converted and then evenly divided into F = 1, it becomes a critical decimation process, and the original structure of the channelized receiver is shown in When The input signal is first modulated and then shifted to baseband. Afterward, it undergoes low-pass filtering and decimation before being fed into subsequent modules for further processing. However, at this stage, the filtering operation occurs before decimation, leading to redundant computations during signal processing. Moreover, convolution operations must be completed within a single sampling period. To address these issues, an alternative approach is proposed, which involves swapping the positions of filtering and decimation operations. This way, the computational requirements of various modules in the system can be met more efficiently.Multi-rate signal processing with the polyphase filtering technique plays a crucial role in reducing the complexity of signal rate conversion and lowering system design complexity. The key process in this technique is subchannelization, where the target monitoring frequency band is divided according to certain rules, and different partitioning methods correspond to different system complexities, computational loads, and resource consumption. In this design, the filter group adopts a 50% overlapping partitioning method , as shows(n), the output The DFT-based polyphase channelization algorithm is developed based on the channelization structure of the low-pass filter bank. Given the input signal Now, let Convert part of the relationship in Equation (3) to:The center frequency of each subchannel in the filter bank under the even-indexed arrangement is:Substituting Equation (5) into Equation (4), we obtain:Substituting Equation (6) into Equation (3), we obtain:In the above equation, DFT represents discrete Fourier transform, which can be replaced by fast Fourier transform (FFT) in hardware implementation to reduce hardware resource consumption and improve system operation speed. The improved structure is shown in the following The proposed joint-decision process for eliminating channel ambiguity in the channelized receiver involves “Instantaneous Feature Extraction + Auto-Correlation Threshold Amplitude Detection + Phase Differential Instantaneous Frequency Measurement”. In the instantaneous feature extraction step, the coordinate rotation digital computer (CORDIC) algorithm is used to extract the instantaneous amplitude and phase information of the channelized output signal in vector mode. Traditional amplitude detection methods compare the signal amplitude with a fixed threshold value to determine the presence of signals in the channel . In thisThe CORDIC  algorithm calculates the amplitude and phase information of the output signal through iterative rotations . The solβ represents the threshold coefficient, The instantaneous frequency of the output signal can be obtained using the phase difference instantaneous frequency measurement method, where the relationship between instantaneous frequency and instantaneous phase is given by Equation (10):The entire decision-making process is as follows:Set the detection threshold Use the signal amplitude calculated from the CORDIC module as input. To reduce the impact of the signal-to-noise ratio, consider a signal to be present in the channel if the amplitude values Finally, perform a phase-difference-based instantaneous frequency estimation for the channel. The frequency deviation value Simulation Conditions: In MATLAB, the input signal is set as the sum of four signals from The channelized output results are shown in For the channels with detected signals, the extracted amplitude, phase, and frequency information are shown in Amplitude extraction result for channel 3, Phase extraction result for channel 3, Amplitude extraction result for channel 14 and Phase extraction result for channel 14. From left to right in The hardware implementation of the wideband digital channelized receiver primarily focuses on the large-scale and high-speed digital signal processing. The hardware platform is based on the Zynq UltraScale + RFSoC series chip, specifically the ZU27DR, which includes high-speed ADC and FPGA sections. The improved scheme of the entire receiver system is shown in In the HLS platform, when implementing the data extraction and routing module, input data can be stored in a multi-dimensional array based on the storage format of the data stream. During the transformation process, the input data needs to be rearranged by columns for parallel computation. Optimization directives can be added during the C Synthesis stage to reduce system latency . Since tIn HLS, when designing the polyphase filtering module, the prototype filter coefficients need to be stored in an array. The coefficients are stored in an array of size ). The implementation process of polyphase filtering is similar to convolution in the time domain, with the only difference being that FIR filtering requires zero padding at the end of the input sequence and uses a circular right shift to align the first item of the input sequence with the first item of the coefficient. Each right shift requires a multiplication operation, and the multiplication results are stored in registers. The final accumulated result is the output of the FIR filter. The polyphase filtering module consists of 16 parallel channels, and since the structure of each channel is the same except for the coefficients and input data, the implementation process of any sub-channel is shown in Due to the high throughput requirements of the data output from the multi-phase filtering structure during FFT computation, a parallel FFT module that can perform parallel computation is needed . HoweverThe CORDIC algorithm has three hardware implementation architectures: serial architecture, parallel architecture, and parallel pipeline architecture. These three architectures are based on the same basic structure of processing units, but operate at different shift amounts and storage angles, resulting in different implementation methods. In this paper, the parallel pipeline architecture is chosen for its design, which consumes significantly more hardware resources compared to the serial architecture.By adding pipeline registers between each iteration, the processing speed of the system can be effectively improved, reducing the critical path length from N processing units in the parallel architecture to 1 processing unit in the pipeline architecture.After obtaining the phase of the complex signal through the CORDIC module, the instantaneous frequency of the signal is calculated using the phase-difference-based frequency estimation algorithm, as shown in The ChipScope, an integrated logic analyzer provided by Xilinx, was used to observe the signal, as described in . In MATLThe data shown in The MATLAB simulation result and timing simulation result of the polyphase filter module are shown in The final channelized output result is shown in the In addition, a chirp signal with a center frequency of 875 MHz and a bandwidth of 10 MHz was generated for the simulation of instantaneous feature extraction. The simulation results, depicted in In this paper, an improved channel decision method has been proposed to address the issue of false signals in communication receivers based on the theory of blind-spot-free reception in a polyphase filtering structure. The method combines instantaneous feature extraction, the adaptive detection of signal amplitude, and phase difference frequency measurement algorithms to transform the process of eliminating false signals into extracting amplitude, phase, and frequency information from the output signal. This new approach improves the discrimination of useful signals and is more easily implemented on FPGA. Additionally, the hardware implementation of the receiver is optimized for speed and latency using HLS high-level synthesis technology, which significantly shortens the development cycle compared to traditional FPGA development processes. The simulation results confirm the practical value of this method for wideband digital receivers.