Prospects for the Application of Transplantation With Human Amniotic Membrane Epithelial Stem Cells in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.

Successful complementary therapy with traditional Chinese medicine in a patient with Qi and Jin deficiency symptoms from adult-onset Still's disease: A case report.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare yet well-documented polygenic and systemic autoinflammatory disease characterized by recurrent spiking fever, transient skin rash, arthralgia, and sore throat. Traditional Chinese medicine (TCM) holds a significant role in complementary and alternative medicine. This study presents a unique case of a female AOSD patient with concurrent Qi and fluid deficiency syndrome who received combined treatment with formulated Zhu Ye Shi Gao Decoction (ZYSGD). CASE PRESENTATION: In this case, a 28-year-old female patient presented with a 15-day history of fever and skin rash accompanied by sore throat, fatigue, myalgia, and arthralgia. Additionally, leucocytosis, aminotransferase abnormalities, and elevated inflammatory factor levels were observed. Infectious diseases, solid tumors, and hematological disorders were all ruled out. Anti-infective treatments proved ineffective, leading to the final diagnosis of AOSD. Glucocorticoid therapy provided only partial relief. Consequently, formulated ZYSGD and hepatoprotective drugs were added to the glucocorticoid treatment. Subsequently, the patient's symptoms and inflammatory biomarkers showed improvement. After discharge, the patient's condition remained stable while continuing the formulated ZYSGD in combination with 4 mg of Medrolol (qd) during a 10-month follow-up period. CONCLUSION: This case report suggests that formulated ZYSGD could be a viable option for complementary and alternative therapy for late-stage AOSD, especially in cases involving both Qi and body fluid imbalances.

Widespread Distribution of the arsO Gene Confers Bacterial Resistance to Environmental Antimony.

Microbial oxidation of environmental antimonite (Sb(III)) to antimonate (Sb(V)) is an antimony (Sb) detoxification mechanism. Ensifer adhaerens ST2, a bacterial isolate from a Sb-contaminated paddy soil, oxidizes Sb(III) to Sb(V) under oxic conditions by an unknown mechanism. Genomic analysis of ST2 reveals a gene of unknown function in an arsenic resistance (ars) operon that we term arsO. The transcription level of arsO was significantly upregulated by the addition of Sb(III). ArsO is predicted to be a flavoprotein monooxygenase but shows low sequence similarity to other flavoprotein monooxygenases. Expression of arsO in the arsenic-hypersensitive Escherichia coli strain AW3110Δars conferred increased resistance to Sb(III) but not arsenite (As(III)) or methylarsenite (MAs(III)). Purified ArsO catalyzes Sb(III) oxidation to Sb(V) with NADPH or NADH as the electron donor but does not oxidize As(III) or MAs(III). The purified enzyme contains flavin adenine dinucleotide (FAD) at a ratio of 0.62 mol of FAD/mol protein, and enzymatic activity was increased by addition of FAD. Bioinformatic analyses show that arsO genes are widely distributed in metagenomes from different environments and are particularly abundant in environments affected by human activities. This study demonstrates that ArsO is an environmental Sb(III) oxidase that plays a significant role in the detoxification of Sb(III).

Differential responses in the mirror neuron system during imitation of individual emotional facial expressions and association with autistic traits.

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Public exposure to broadband electromagnetic fields and its association with population density and building density: The case study of Beijing.

The gradual increase in electromagnetic field (EMF) exposure levels poses a potential threat to human health and the normal operation of electronic systems. In order to know the environmental EMF conditions, measurements were carried out on roads of about 400 km in the urban area of Beijing, China. The measurement results show that the electric field strength of about 89% of the sampling points is within 3 V/m, and the electric field strength of other sampling points is relatively high. Combined with further spectrum analysis, it was found that the electric field strength of one road section exceeded the national standard limits. In addition, to help quickly identify the general condition of the environmental EMF, a set of procedures for mining the association rules between the electric field strength and population density and building density is proposed in this paper. The final association rules show that the electric field strength is usually lower than 1.5 V/m in areas with medium or lower population density and areas with low building density; the electric field strength in areas with extremely high population density and areas with high building density is usually 1.5-4 V/m; while the electric field strength higher than 4 V/m mainly occurs in areas with extremely high population density. It is recommended to focus on strengthening the monitoring of EMF in areas with extremely high population density, and at the same time continuously pay attention to the trend of the urban EMF levels, so as to achieve early warning and treatment of relevant risks.

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use.

BACKGROUND AND AIMS: Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward circuitry or social brain, and associations with levels of problematic smartphone or social media use. METHODS: We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding analyses were employed to further characterize the identified regions. RESULTS: Higher levels of FOMO associated with lower cortical thickness in the right precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analytic decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. DISCUSSION AND CONCLUSIONS: Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN and involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

Ecological drivers and potential functions of viral communities in flooded arsenic-contaminated paddy soils.

This work revealed the profile of viral communities in paddy soils with different levels of arsenic (As) contamination during the flooded period. The structure of viral communities differed significantly in highly and moderately As-contaminated soils. The diversity of soil viral communities under high As contamination decreased. Siphoviridae, Podoviridae, Myoviridae, and Microviridae were the dominant viral families in all samples, and the relative abundances of five of the top 20 viral genera were significantly different between highly and moderately As-contaminated groups. Seventeen dissimilatory As(V)-reducing bacteria were predicted to host 161 viral operational taxonomic units (vOTUs), mainly affiliated with the genera of Sulfurospirillum, Deferribacter, Bacillus and Fusibacter. Among them, 28 vOTUs were also associated with Fe(III)-reducing bacteria, which belonged to different species of the genus Shewanella. Procrustes analysis showed that the community structure of soil viruses was strongly correlated with both prokaryotic community structure and geochemical properties. Random forest analyses revealed that the Total-Fe, DCB-Fe and oxalate-Fe were the most significant variables on viral community richness, while the total-As concentration was an important factor on the Shannon index. Furthermore, As resistance genes (ArsC, ArsR and ArsD), As methylation genes (arsM) and As transporter genes (Pst and Pit) were identified among the auxiliary metabolic genes (AMGs) of the virome. This work revealed that the viruses might influence microbial adaptation in response to As-induced stress, and provided a perspective on the potential virus-mediated biogeochemical cycling of As.

Regional superficial amygdala resting-state functional connectivity in adults infers childhood maltreatment severity.

Background: Childhood maltreatment (CM) is a potential risk factor for some neuropsychiatric disorders in adulthood (e.g. depression and anxiety) and alters trajectories of brain development. Accumulating evidence suggests that functional connectivity of the limbic system, especially the amygdala, is highly associated with childhood maltreatment, although not all studies have found this. These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity (rsFC) following childhood maltreatment. Objective: Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity, as well as to develop a stable rsFC-based model for inferring the severity of CM. Methods: In this study, we employed the Childhood Trauma Questionnaire (CTQ) to assess CM severity in each individual. We explored the relationship between the rsFC of amygdala subregions (i.e. centromedial -CMA, basolateral -BLA, superficial-SFA amygdala) and CM experience in a discovery dataset of n = 110 healthy Chinese participants by linear multiple regression analysis. Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes, respectively. A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores. Moreover, we also verified the model into another independent replication dataset (n = 38). Results: Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amygdala and perigenual anterior cingulate cortex (pgACC)/postcentral gyrus (PCG) but not the other two amygdala subregions. Moreover, SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect. In addition, supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets. Conclusion: The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders (i.e. depression and anxiety).

Analysis on the interactions between the first introns and other introns in mitochondrial ribosomal protein genes.

It is realized that the first intron plays a key role in regulating gene expression, and the interactions between the first introns and other introns must be related to the regulation of gene expression. In this paper, the sequences of mitochondrial ribosomal protein genes were selected as the samples, based on the Smith-Waterman method, the optimal matched segments between the first intron and the reverse complementary sequences of other introns of each gene were obtained, and the characteristics of the optimal matched segments were analyzed. The results showed that the lengths and the ranges of length distributions of the optimal matched segments are increased along with the evolution of eukaryotes. For the distributions of the optimal matched segments with different GC contents, the peak values are decreased along with the evolution of eukaryotes, but the corresponding GC content of the peak values are increased along with the evolution of eukaryotes, it means most introns of higher organisms interact with each other though weak bonds binding. By comparing the lengths and matching rates of optimal matched segments with those of siRNA and miRNA, it is found that some optimal matched segments may be related to non-coding RNA with special biological functions, just like siRNA and miRNA, they may play an important role in the process of gene expression and regulation. For the relative position of the optimal matched segments, the peaks of relative position distributions of optimal matched segments are increased during the evolution of eukaryotes, and the positions of the first two peaks exhibit significant conservatism.

AsgeneDB: a curated orthology arsenic metabolism gene database and computational tool for metagenome annotation.

Arsenic (As) is the most ubiquitous toxic metalloid in nature. Microbe-mediated As metabolism plays an important role in global As biogeochemical processes, greatly changing its toxicity and bioavailability. While metagenomic sequencing may advance our understanding of the As metabolism capacity of microbial communities in different environments, accurate metagenomic profiling of As metabolism remains challenging due to low coverage and inaccurate definitions of As metabolism gene families in public orthology databases. Here we developed a manually curated As metabolism gene database (AsgeneDB) comprising 400 242 representative sequences from 59 As metabolism gene families, which are affiliated with 1653 microbial genera from 46 phyla. AsgeneDB achieved 100% annotation sensitivity and 99.96% annotation accuracy for an artificial gene dataset. We then applied AsgeneDB for functional and taxonomic profiling of As metabolism in metagenomes from various habitats (freshwater, hot spring, marine sediment and soil). The results showed that AsgeneDB substantially improved the mapping ratio of short reads in metagenomes from various environments. Compared with other databases, AsgeneDB provides more accurate, more comprehensive and faster analysis of As metabolic genes. In addition, we developed an R package, Asgene, to facilitate the analysis of metagenome sequencing data. Therefore, AsgeneDB and the associated Asgene package will greatly promote the study of As metabolism in microbial communities in various environments.

Language Skill Differences Further Distinguish Social Sub-types in Children with Autism.

This study investigated heterogeneity in language skills of children with autism and their relationship with different autistic social subtypes. Data from 90 autistic and 30 typically developing children were analyzed. Results showed that autistic social subtypes varied in language skill problems (aloof > passive > active-but-odd). There was a negative association between aloof dimension scores and language performance but positive for the active-but-odd dimension and no association in the passive one. Moreover, aloof dimension score was the main contributor to language performance. A receiver operating characteristic analysis suggested language vocabulary as an additional component in differentiating autistic social subtypes. These findings demonstrate that variations in language skills in autistic children provide additional information for discriminating their social subtype.

Scorpion venom polypeptide governs alveolar macrophage M1/M2 polarization to alleviate pulmonary fibrosis.

The onset of connective tissue disease-related interstitial lung disease (CTD-ILD) is generally insidious and progressive, with pulmonary fibrosis in the middle stage, and eventually respiratory failure and death. This study aimed to explore the role of scorpion venom polypeptide (SVP), the primary active constituent of the entire scorpion, in alveolar macrophages and pulmonary fibrosis. Pulmonary fibrosis mouse models were established, and then SVP and JAK inhibitor (tofacitinib) was used to treat models. Alveolar macrophages were isolated and the impacts of SVP on M1/M2 polarization and the JAK/STAT6 pathway in vitro were assessed. H&E and Masson staining revealed that SVP and tofacitinib treatment alleviated lung damage and fibrosis. They also hindered the M2-polarization of macrophages in lung tissue and declined cytokine levels associated with M2 polarization (IL-4, IL-13) and fibrosis drivers (TGF-ß, VEGF) in mice. Consistent with the trend presented by tofacitinib treatment, SVP suppressed the phosphorylation of proteins in the JAK/STAT6 pathway. In addition, the in vitro treatment of SVP on the isolated macrophages represented consistent results with in vivo experiments. The findings of the present study indicated that SVP suppressed the JAK/STAT6 signaling pathway, hindered alveolar macrophage M2-type polarization, and possessed the potential to ameliorate pulmonary fibrosis.

Investigation of the mechanism of action of Shengxuexiaoban Capsules against primary immune thrombocytopenia using network pharmacology and experimental validation.

BACKGROUND: Shengxuexiaoban Capsules (SC) is a classical prescription in traditional Chinese medicine (TCM) and has been clinically adopted in the treatment of primary immune thrombocytopenia (ITP) in China. However, the underlying mechanisms of the actions of SC on ITP remain clear. METHODS: A network pharmacology approach was adopted to investigate the underlying molecular mechanism of SC in treating ITP, and the effects of SC on the proliferation, differentiation, and apoptosis of megakaryocyte (MK) and on the ITP animal model were investigated. RESULTS: Network pharmacology analysis found 128 active compounds and 268 targets of these compounds in SC, as well as 221 ITP-related targets. The topological analysis found a central network containing 82 genes, which were significantly associated with the regulation of transcription, cell proliferation, apoptosis processes, the PI3K-AKT signaling pathway, the MAPK signaling pathway, and the ERK1 and ERK2 cascades. It showed that SC increased the proliferation and differentiation of MK, but had no significant impact on MK apoptosis in vivo. The addition of SC increased the gene expression of several potential targets, including STAT3, KDR, CASP3, and TGFB1. In addition, SC administration elevated the protein expression of p-AKT and inhibit the protein expression of p-ERK, but has no impact on the protein expression of p-P38. Moreover, SC could improve haemogram parameters, coagulation indicators, and the proliferation and differentiation of MK in the ITP animal model. CONCLUSIONS: The present study systematically elucidated the underlying mechanisms of SC against ITP and provided an efficient strategy to discover the pharmacological mechanism of TCM. It may strengthen the understanding of SC and facilitate more application of this formula in the treatment of ITP.

Own Race Eye-Gaze Bias for All Emotional Faces but Accuracy Bias Only for Sad Expressions.

Own race faces tend to be recognized more accurately than those of other less familiar races, however, findings to date have been inconclusive. The present study aimed to determine whether Chinese exhibit different recognition accuracy and eye gaze patterns for Asian (own-race) and White (other-race) facial expressions (neutral, happiness, sadness, anger, disgust, fear). A total of 89 healthy Chinese adults viewed Asian and White facial expressions while undergoing eye-tracking and were subsequently required to identify expressions and rate their intensity and effect on arousal. Results revealed that subjects recognized sad expressions in Asian faces better than in White ones. On the other hand, recognition accuracy was higher for White neutral, happy, fearful, and disgusted expressions although this may have been due to subjects more often misclassifying these Asian expressions as sadness. Moreover, subjects viewed the eyes of emotional expressions longer in Asian compared to White faces and the nose of sad ones, especially during the late phase of presentation, whereas pupil sizes, indicative of cognitive load and arousal, were smaller. Eye-gaze patterns were not, however, associated with recognition accuracy. Overall, findings demonstrate an own-race bias in Chinese for identifying sad expressions and more generally across emotional expressions in terms of viewing the eye region of emotional faces for longer and with reduced pupil size. Interestingly, subjects were significantly more likely to miss-identify Asian faces as sad resulting in an apparent other-race bias for recognizing neutral, happy, fearful, and disgusted expressions.

Hypertrophic pachymeningitis with co-occurrence of anti-neutrophil cytoplasmic antibodies and immunoglobulin G4 seropositivity: Case report and literature review.

We report an extremely rare case of hypertrophic pachymeningitis in which a 71-year-old man presented with an intractable recurrent headache for >1 year. During this period, he became positive for immunoglobulin G4 and proteinase 3-antineutrophil cytoplasmic antibodies. Contrast-enhanced magnetic resonance imaging showed characteristic diffuse thickening of the dura. Symptoms were improved by intravenous methylprednisolone (500 mg per day for 5 days) and cyclophosphamide pulse therapy during corticosteroid withdrawal; he remained symptom-free during 1-year follow-up. This case suggests that this disease can be treated by corticosteroids combined with immunosuppressive agents.

Eltrombopag improves refractory thrombocytopenia in patients with Sjögren's syndrome.

INTRODUCTION: Eltrombopag, a kind of thrombopoietin (TPO) receptor agonist, plays the role on the megakaryocyte to activate the platelet production and rapidly increase the number of circulating platelets in patients with primary immune thrombocytopenia (ITP). Eltrombopag provides an opportunity for rapid tapering and/or cessation of corticosteroid therapy. However, it is not clear about the platelet response to Eltrombopag in ITP associated with Sjögren's Syndrome(SS). METHODS: A retrospective research was conducted on the clinical course of three patients, each with ITP secondary to SS, and initially received therapy of corticosteroids or other immunomodulatory. They took this drug for bleeding diseases. Referring to the description, Eltrombopag was prescribed and adjusted with an initial dose of 25 mg daily, then weekly, then monthly according to the monitoring of platelet counts. RESULTS: All patients maintained a satisfactory level of platelet counts (>100,000/mm3 for >2 years) following corticosteroid withdrawal. Meanwhile, Eltrombopag was well-tolerated, and there were no adverse effects, such as thrombotic events. CONCLUSIONS: Eltrombopag is effective and safe for patients with ITP associated with SS during corticosteroid withdrawal. Thus it may be a crucial therapeutic strategy for reducing corticosteroid-related side effects in SS patients with ITP.

Depression mediates the association between insula-frontal functional connectivity and social interaction anxiety.

High rates of comorbidity between depression and anxiety are frequently observed. However, few studies have investigated the relationship between depression and social interaction anxiety using a dimensional approach. The current study aimed to explore the associations between depression and social interaction anxiety with a multivariate approach in a comparably large dataset (n = 194, 95 males). All participants completed a structural and a resting-state functional magnetic resonance imaging (fMRI) scan and self-report measures of depression via Beck's Depression Inventory II and social interaction anxiety by social interaction anxiety scale. Voxel-based morphometry (VBM) results first identified grey matter volumes of insula were positively correlated with depression dimension scores. Next, whole brain seed-to-voxel analyses were conducted using a VBM-identified insula as a seed region to examine associations between depression/social anxiety and functional connectivity. The results suggested that a significant positive effect of depression/social anxiety was found on the connectivity between insula and dorsal lateral prefrontal cortex (dlPFC). Moreover, variations in depression meditated the association between insula-dlPFC connectivity and social interaction anxiety. Overall, the results indicate that individual differences in depression relate more to insula-dlPFC coupling compared to social interaction anxiety.

Scorpion Venom Polypeptide Inhibits Pulmonary Epithelial-Mesenchymal Transition in Systemic Sclerosis-Interstitial Lung Disease Model Mice by Intervening TGF-ß1/Smad Signaling Pathway.

Objective: Interstitial lung disease (ILD) is an important complication of systemic sclerosis (SSc). The aim of this study was to investigate the effect and possible mechanism of polypeptide extract of scorpion venom (PESV) on SSc-ILD. Methods: C57/BL6 mice were injected with bleomycin to establish a SSc-ILD model. Different concentrations of PESV solution were administered to SSc-ILD mice, and dexamethasone was used as a positive control. H&E staining and Masson staining were used to observe the pathological changes. The TGF-ß1 expression level was detected by immunohistochemistry. The expression of epithelial-mesenchymal transition (EMT)-related proteins was detected by Western blot, and the expression of TGF-ß1/Smad pathway-related proteins was also detected. The content of inflammatory cytokines in serum and BALF was determined by ELISA. Results: Pathological analysis showed that PESV could alleviate SSc-ILD-induced pulmonary inflammation and fibrosis. Compared with the model group, the content of inflammatory cytokines IL-6 and TNF-α significantly decreased after PESV treatment. PESV could increase the expression of epithelial marker (E-cadherin) and reduce the expression of interstitial markers (collagen I, vimentin, N-cadherin, and a-SMA). In addition, PESV could reduce the expression level of TGF-ß1/Smad pathway-related protein. Conclusion: PESV can attenuate SSc-ILD by regulating EMT, and the effect was linked to the TGF-ß1/Smad signaling pathway, which indicated that PESV may serve as a candidate drug for SSc-ILD.

Associations between levels of Internet Gaming Disorder symptoms and striatal morphology-replication and associations with social anxiety.

Background: Brain structural alterations of the striatum have been frequently observed in internet gaming disorder (IGD); however, the replicability of the results and the associations with social-affective dysregulations such as social anxiety remain to be determined. Methods: The present study combined a dimensional neuroimaging approach with both voxel-wise and data-driven multivariate approaches to (i) replicate our previous results on a negative association between IGD symptom load (assessed by the Internet Gaming Disorder Scale-Short Form) and striatal volume, (ii) extend these findings to female individuals, and (iii) employ multivariate and mediation models to determine common brain structural representations of IGD and social anxiety (assessed by the Liebowitz Social Anxiety Scale). Results: In line with the original study, the voxel-wise analyses revealed a negative association between IGD and volumes of the bilateral caudate. Going beyond the earlier study investigating only male participants, the present study demonstrates that the association in the right caudate was comparable in both the male and the female subsamples. Further examination using the multivariate approach revealed regionally different associations between IGD and social anxiety with striatal density representations in the dorsal striatum (caudate) and ventral striatum (nucleus accumbens). Higher levels of IGD were associated with higher social anxiety and the association was critically mediated by the multivariate neurostructural density variations of the striatum. Conclusions: Altered striatal volumes may represent a replicable and generalizable marker of IGD symptoms. However, exploratory multivariate analyses revealed more complex and regional specific associations between striatal density and IGD as well as social anxiety symptoms. Variations in both tendencies may share common structural brain representations, which mediate the association between increased IGD and social anxiety.