Targeting the TRAF3-ULK1-NLRP3 regulatory axis to control alveolar macrophage pyroptosis in acute lung injury.

Acute lung injury (ALI) is a serious condition characterized by damage to the lungs. Recent research has revealed that activation of the NLRP3 inflammasome in alveolar macrophages, a type of immune cell in the lungs, plays a key role in the development of ALI. This process, known as pyroptosis, contributes significantly to ALI pathogenesis. Researchers have conducted comprehensive bioinformatics analyses and identified 15 key genes associated with alveolar macrophage pyroptosis in ALI. Among these, NLRP3 has emerged as a crucial regulator. This study further reveal that the ULK1 protein diminishes the expression of NLRP3, thereby reducing the immune response of alveolar macrophages and mitigating ALI. Conversely, TRAF3, another protein, is found to inhibit ULK1 through a process called ubiquitination, leading to increased activation of the NLRP3 inflammasome and exacerbation of ALI. This TRAF3-mediated suppression of ULK1 and subsequent activation of NLRP3 are confirmed through various in vitro and in vivo experiments. The presence of abundant M0 and M1 alveolar macrophages in the ALI tissue samples further support these findings. This research highlights the TRAF3-ULK1-NLRP3 regulatory axis as a pivotal pathway in ALI development and suggests that targeting this axis could be an effective therapeutic strategy for ALI treatment.

"I've Spent My Whole Life Striving to Be Normal": Internalized Stigma and Perceived Impact of Diagnosis in Autistic Adults.

Background: Receiving an autism diagnosis in adulthood often leads to improved self-understanding and deeper self-reflection, which can have major impacts on people's well-being and sense of identity. However, autism diagnosis also exposes individuals to societal stigma, which may become internalized over time. This study aimed to explore relationships between psychological and service-related impacts of diagnosis and internalized stigma using mixed methods. Methods: One hundred forty-three autistic adults completed an online survey involving impact of diagnosis domains of Self-Understanding, Well-being, Clinician Support, and Service Access, internalized stigma, and open-ended questions on beliefs about autism diagnosis. Results: On average, participants reported mild levels of internalized stigma and positive impact of diagnosis in all domains except Service Access. Older age at diagnosis was positively associated with Clinician Support only. The path analysis model showed positive relationships between impact of diagnosis domains, with Self-Understanding having a positive effect on Well-being via lowered internalized stigma. We developed four themes of Continuity and Acceptance, Late Diagnosis as Regret and Freedom, Coming to Terms with Being Autistic, and Stigma Resistance from qualitative data. Conclusions: Self-understanding protects against the development of internalized autism stigma. Diagnosticians and service providers play an important role in improving self-understanding and well-being in autistic adults. More research is needed to understand the role of age at diagnosis and mechanisms behind positive identity development after autism diagnosis.

Why is this an important issue?: Receiving an autism diagnosis in adulthood can help people understand themselves better. This can help them feel better too. Autistic adults' experiences during diagnosis and their experience with support services after diagnosis might also affect how they think and feel about themselves. There are many negative beliefs about autism in society. Some autistic people might think more negatively about themselves because of these beliefs. What was the purpose of this study?: This study tries to understand relationships between the impact of autism diagnosis and negative beliefs about autism in autistic adults. We also wanted to know if age at diagnosis is related to these factors. What did the researcher do?: One hundred forty-five autistic adults filled in an online survey. We asked questions about the impact of autism diagnosis on four aspects: how they understand themselves, their well-being, experiences with the professional who gave the diagnosis, and support services after diagnosis. We also asked questions about autistic adults' negative beliefs about autism. We used the answers to these questions to test a model of how we think these factors might affect each other: good experiences with the professional who gave the diagnosis help with self-understanding and getting support services. Better self-understanding helps autistic adults think less negatively about autism. Better self-understanding, less negative thinking about autism, and better support services all help improve well-being after diagnosis.We asked autistic adults some general questions about the effect of autism diagnosis on their lives. We asked autistic adults whether they think being diagnosed at an older or younger age made a difference. We also asked autistic adults about negative beliefs that some autistic people might have about their autism. We then read these answers and made a list of the important and common ideas in people's answers. What were the results of the study?: In general, autism diagnosis improved autistic adults' self-understanding and well-being. Most autistic adults had good experiences with the diagnosing professional but did not have good support services after diagnosis. On average, autistic adults had a small amount of negative beliefs about autism. People diagnosed at older ages had better support from the health professional who diagnosed them. We did not find any other differences between people diagnosed at different ages. We successfully tested our model of relationships between self-understanding, well-being, experiences with the diagnosing professional, experience of support services, and negative beliefs about autism.Autistic adults said getting the diagnosis did not change who they are. It helped them understand and accept themselves. Some late-diagnosed autistic adults wished they were diagnosed earlier. Others said being diagnosed younger might make you think less of yourself because there was less autism acceptance in society at that time. Both early-diagnosed and late-diagnosed autistic adults said growing older helped them understand what it means to be autistic. Autistic adults also talked about autistic and non-autistic people's negative beliefs about autism. Some autistic adults said that negative beliefs are caused by society not being accepting enough, not because autism itself is bad. This thinking helps autistic adults think more positively about autism. What do these findings add to what was already known?: This is the first study to measure and develop a model of the relationships between impacts of diagnosis and negative beliefs about autism in autistic adults. What are potential weaknesses in this study?: Most people who did our survey were diagnosed as teens and adults. It was hard to measure the effects of age at autism diagnosis because we did not have enough participants diagnosed at young ages. The people who did our survey were mostly female, White, spoke English only, and did not have intellectual disability. This means that the people in our study are not a good representation of all autistic adults in Australia. The questions we used to measure negative beliefs about autism were originally made for people with mental illness. There might be negative beliefs specific to autism that we did not measure. How will these findings help autistic adults now or in the future?: Our findings tell professionals who diagnose or support autistic adults that it is important to help autistic adults understand what it means to be autistic in a positive way. This will help autistic adults form more positive beliefs about autism and live happier lives.

Development of the Impact of Diagnosis Scale-Revised (IODS-R).

No tools quantify the experience, psychological, and practical impact of receiving a diagnosis from a non-deficit perspective. Autism is increasingly late diagnosed in adulthood. The Impact of Diagnosis Scale (IODS) was initially developed for borderline personality disorder. We aimed to develop a revised version suitable for autistic adults and potentially other diagnostic groups. Following a trial of a preliminary revision, the researchers and autistic research advisors co-produced an expanded pool of 46 items, scored on 7-point Likert-type scale, within 6 hypothesized domains. Scale reduction processes were applied to data from 125 formally diagnosed autistic adults. Following iterative rounds of factor analysis using maximum likelihood estimation with Promax rotation, 22 items were retained across 4 domains to comprise the IODS-R. The IODS-R adds new understanding to the experience of receiving an autism diagnosis in adulthood. It may be useful for evaluating diagnostic services and other diagnostic groups.

Impact of endoscopic thoracic R4 sympathicotomy combined with R3 ramicotomy for primary palmar hyperhidrosis.

Background: Endoscopic thoracoscopic sympathectomy (ETS) is the preferred method for treating primary palmar hyperhidrosis (PPH) that bears the risk of compensatory hyperhidrosis (CH) following surgery. The current study aims to evaluate the effectiveness and safety of an innovative surgical procedure of ETS. Methods: A survey of the clinical data of 109 patients with PPH who underwent ETS in our department from May 2018 to August 2021 was retrospectively conducted. The patients were organized into two groups. Group A underwent R4 sympathicotomy combined with R3 ramicotomy. Group B underwent R3 sympathicotomy. Patients were followed up to evaluate the safety, effectiveness and the incidence of postoperative CH of the modified surgical approach. Results: A total of 102 patients completed follow-up, and seven of the total enrolled patients were lost to follow-up, with a loss rate of 6% (7/109). Among these, Group A constitutes 54 cases, group B constitutes 48 cases, and the mean follow-up was 14 months (interquartile range 12-23 months). There was no statistically difference in surgical safety, postoperative efficacy, and postoperative quality of life (QoL) score between group A and group B (p > 0.05). The score of the psychological assessment was higher (p = 0.004) in group A (14.15 ± 2.06) compared to group B (13.30 ± 1.86). The incidence of CH in group A was lower than in group B (p = 0.019). Conclusion: R4 sympathicotomy combined with R3 ramicotomy is safe and effective for PPH treatment, along with a reduced incidence of postoperative CH rate and improved postoperative psychological satisfaction.

A Qualitative Study of Adults' and Support Persons' Experiences of Support After Autism Diagnosis.

Adulthood autism diagnosis has become increasingly common, but little is known about post-diagnosis support experiences and needs. We interviewed 19 autistic adults and 4 support persons on experiences of formal and informal post-diagnosis support. Reflexive thematic analysis was used to identify themes. Participants reported difficulties accessing suitable formal support, especially regarding education and employment. Informal support was helpful but created challenges in the relationships between autistic adults and support persons. For autistic adults, support from autistic peers fostered belonging and self-acceptance. We also identified complex interactions between adults' post-diagnosis identity development and support experiences as they resolved the dilemma between self-acceptance and a desire to change. Findings have important implications for services working with autistic adults and their families.

Experiences of Support Following Autism Diagnosis in Adulthood.

This study aimed to explore experiences of support after adulthood autism diagnosis. In this mixed-methods survey study of 137 adults, we found that most common formal supports received were counselling and mental health. Common unmet support needs were sensory sensitivities and accessing other services. Cost, lack of information, and fear of not being taken seriously were common barriers. Informal support was mainly helpful for self-understanding and emotions toward diagnosis. Qualitative findings included difficulties accessing formal support, need for practical quality-of-life supports and support from autistic peers and online communities. Based on these findings, future development of supportive interventions should address unmet needs, improve access, and explore the integration of autistic peer support and online support into formal services.

Autistic Adults' Experiences of Diagnosis Disclosure.

As autism is an invisible and often stigmatised condition, disclosing the diagnosis may lead to both support and/or discrimination. This mixed-methods questionnaire study examined autistic adults' experiences of disclosure in various contexts. The sample consisted of 393 participants aged 17-83 years from two longitudinal surveys. Almost all participants disclosed their diagnosis to someone, most commonly to friends. A significant minority of participants studying and/or working at the time had not disclosed to their education provider/employer. Content analysis of open-ended responses showed participants desired to gain understanding and support from disclosure but feared prejudice. While some received support, others encountered dismissiveness and misunderstanding. Findings highlight the need to improve autism understanding and reduce stigma within and beyond educational and employment contexts.

Choose your Own Adventure: Pathways to Adulthood Autism Diagnosis in Australia.

Pathways to diagnosis in adulthood are poorly understood. Even less is known about undiagnosed adults who believe they may be autistic. This mixed-methods online survey examined adults' journeys from initial concern to receiving the diagnosis. Quantitative findings showed the diagnostic process to be highly heterogeneous. Qualitative analysis identified desires for explanation and support as motives for seeking diagnosis. Cost and fear of not being taken seriously were major barriers, echoed by qualitative responses that described the process as confusing, expensive and time-consuming. While most participants were satisfied with the diagnosis, their emotional reactions were complex. Findings support the need for thoroughly implementing national guidelines, and for improved knowledge and communication in mainstream clinicians encountering clients with possible autism characteristics.

Factors associated with age at autism diagnosis in a community sample of Australian adults.

Autism diagnosis in adulthood has become increasingly common due to a range of factors including changes in awareness, diagnostic criteria, and professional practices. Past research identified a range of demographic and autism-related factors associated with autism diagnosis age in children. However, it is unclear whether these apply to autistic adults. This study aimed to examine predictors of autism diagnosis age in adults while controlling for current age and autistic traits. We used a cross-sectional sample of 657 adults aged 15-80 from three self and carer-report studies: the Australian Longitudinal Study of Autism in Adulthood (ALSAA), Study of Australian School-Leavers with Autism (SASLA) and Pathways, Predictors and Impact of Receiving an Autism Spectrum Diagnosis in Adulthood (Pathways). Using hierarchical multiplicative heteroscedastic regression, we found that older current age and higher self-reported autistic traits predicted older diagnosis age, and that female gender, lack of intellectual disability, language other than English, family history of autism, lifetime depression, and no obsessive-compulsive disorder predicted older diagnosis age beyond current age and autistic traits. The paradoxical relationship between high autistic traits and older diagnosis age requires further investigation. Based on these findings, we recommended strategies to improve autism recognition in women and people from non-English-speaking backgrounds. Future studies could extend the findings by examining the effects of childhood and adulthood socioeconomic status on adult diagnosis age. LAY SUMMARY: We studied the relationship between age at autism diagnosis and other characteristics in adults. We found that both older current age and higher autistic traits, female gender, language other than English, family history of autism, and history of depression were related to older age at diagnosis, while intellectual disability and history of obsessive-compulsive disorder were related to younger age at diagnosis. Our findings suggest more work is needed to help recognize autism in women and people from non-English-speaking backgrounds.

Circ_0006168 Promotes the Migration, Invasion and Proliferation of Esophageal Squamous Cell Carcinoma Cells via miR-516b-5p-Dependent Regulation of XBP1.

BACKGROUND: Circular RNAs (circRNAs) exert important roles in carcinogenesis. Here, we aimed to uncover the working mechanism of circ_0006168 in esophageal squamous cell carcinoma (ESCC) development. METHODS: Western blot assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine protein and RNA expression, respectively. Wound healing assay and transwell migration assay were performed to assess cell migration ability, whereas cell invasion ability was evaluated by transwell invasion assay. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were utilized to analyze cell proliferation ability. Xenograft tumor model was utilized to assess the role of X-box binding protein 1 (XBP1) in xenograft tumor growth in vivo. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to verify intermolecular interactions. RESULTS: XBP1 silencing suppressed the migration, invasion and proliferation of ESCC cells in vitro and restrained the xenograft tumor growth in vivo. MicroRNA-516b-5p (miR-516b-5p) interacted with the 3' untranslated region (3'UTR) of XBP1 in ESCC cells. MiR-516b-5p overexpression inhibited the proliferation and motility of ESCC cells. MiR-516b-5p was a molecular target of circ_0006168 in ESCC cells. The interference of circ_0006168 restrained the motility and proliferation of ESCC cells. Circ_0006168 acted as miR-516b-5p sponge to up-regulate XBP1 expression in ESCC cells. MiR-516b-5p silencing or the accumulation of XBP1 largely rescued the proliferation ability and motility in circ_0006168-silenced ESCC cells. CONCLUSION: In conclusion, circ_0006168 contributed to ESCC development through promoting the proliferation and motility of ESCC cells via mediating miR-516b-5p/XBP1 axis.

Silencing of UAP1L1 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the malignant tumors with poor prognosis. UAP1L1 (UDP-N-acetylglucosamine-1-like-1) affects numerous biological processes, which is a key regulator of the development of malignant tumors. The biological function and molecular mechanism of UAP1L1 in ESCC were explored in this study. The relationship between UAP1L1 and ESCC was analyzed by immunohistochemical staining, revealing the high expression of UAP1L1 in ESCC. Importantly, the increased expression of UAP1L1 indicated the deterioration of patients' condition, which has clinical significance. Furthermore, the loss-of-function assays demonstrated that knockdown of UAP1L1 inhibited the progression of ESCC on suppressing proliferation, hindering migration, and enhancing apoptosis in vitro. Moreover, the apoptosis of ESCC cells was induced by knockdown of UAP1L1 via regulating a variety of apoptosis-related proteins, such as upregulation of Bax, CD40, CD40L, Fas, FasL, IGFBP-6, p21, p27, p53, and SMAC. Additionally, further investigation indicated that UAP1L1 by affecting the PI3K/Akt, CCND1, and MAPK promotes the progression of ESCC. In vivo xenograft model further confirmed that knockdown of UAP1L1 inhibited the development of ESCC. In conclusion, UAP1L1 was involved in the development and progression of ESCC, which may provide a powerful target for future molecular therapies.

Overexpression of close homolog of L1 enhances the chemosensitivity of lung cancer cells via inhibition of the Akt pathway.

Drug resistance leads to tumor relapse and further progression during chemotherapy in lung cancer. Close homolog of L1 (CHL1) has been identified as a tumor suppressor in most malignancies. However, to the best of our knowledge, whether CHL1 mediates chemoresistance remains unknown. The present study observed that CHL1 was significantly downregulated in cisplatin (DDP)-resistant cells (A549/DDP) and paclitaxel (PTX)-resistant cells (A549/PTX) compared with A549 cells. When treated with or without DDP and PTX, silencing of CHL1 in A549 cells promoted the cell survival rate and clone formation, and decreased apoptosis. Whereas overexpression of CHL1 in A549/DDP and A549/PTX cells impeded the cell survival and clone formation and promoted apoptosis. Additionally, CHL1 overexpression enhanced the chemosensitivity of A549/DDP cells to DDP in vivo. Notably, the chemoresistance induced by CHL1 depletion was reversed by the Akt inhibitor SC66 in A549 cells. The results of the present study demonstrated that CHL1 enhanced sensitivity of lung cancer cells by suppressing the Akt pathway, which suggested that CHL1 may be a potential target for overcoming chemoresistance in lung cancer.

Diagnosis of autism in adulthood: A scoping review.

LAY ABSTRACT: More adults are getting assessed for possible autism. Here, we give an overview on what is already known about autism diagnosis in adulthood and find areas that need more research. We divided results from the studies we found into six topics of (1) rates of autism in different groups; (2) the process of getting an autism diagnosis in adulthood; (3) gender; (4) personality traits, abilities and behaviours of diagnosed adults; (5) mental and physical health conditions that occur together with autism; and (6) how adults think and feel about being assessed and diagnosed. We found that adults often have strong emotions after being diagnosed, the process of getting a diagnosis can be unclear and different for everyone, and not many support services are available for adults. More research on diagnosing adults with intellectual disability, differences between early and late-diagnosed adults, and support after diagnosis would be useful.

"The Single Most Important Thing That Has Happened to Me in My Life": Development of the Impact of Diagnosis Scale-Preliminary Revision.

Background: Awareness and diagnosis of autism in adulthood is on the rise. Studies have considered the impact of receiving an autism diagnosis for parents of children on the spectrum, although only few primarily qualitative studies have considered the self-reported impact of autism diagnosis. The Impact of Diagnosis Scale (IODS) was initially developed with a focus on borderline personality disorder. Our aim was to develop a version suitable for autistic individuals. Methods: The research team and a group of autistic advisors revised the IODS items for suitability and accessibility to autistic participants. We gathered participant data for 92 autistic adolescents and adults from the Cooperative Research Centre for Living with Autism (Autism CRC) Study of Australian School Leavers with Autism (SASLA) and the Australian Longitudinal Study of Autism in Adulthood (ALSAA). We used iterated principal factors analysis to explore potential factors, and thematic analysis to explore responses to two open-ended items. Results: Factor analysis suggested three factors of "Service Access (SA)," "Being Understood (BU)," and "Self-Acceptance and Understanding (SU)" for the 12 items of the IODS-Preliminary Revision (IODS-PR). Cronbach's alpha was good overall and acceptable for subdomains. Item mean scores suggest that although impact of autism diagnosis was generally perceived as positive for SU, scores were neutral in other domains. Qualitative analysis identified themes of Self-Understanding, Identity, and Acceptance, Supports and Services, Valence of Response, Relationships, and Camouflaging. Conclusions: The IODS-PR is the first scale to measure the self-reported experience of receiving an autism diagnosis. It showed good psychometrics and provides new insight into the experience of autism diagnosis. Qualitative analysis identified domains that remain unexplored and the potential for an expanded item set. A further revision of the tool will soon be available. It will provide critical information for clinicians and has potential applications for research and service evaluation. Lay summary: Why was this study done?: There are increasing numbers of adults who are only diagnosed with autism in their teen and adult years. Research on this topic is limited, with most using surveys or interviews.What was the purpose of this study?: The purpose was to develop a revision of the Impact of Diagnosis Scale (IODS) to make it suitable to autistic teenagers and adults.What did the researchers do?: We worked with autistic research advisors to create the IODS-Preliminary Revision (IODS-PR), which has 12 items scored on a 7-point agree/disagree scale and two open-ended questions. We then gathered data using the IODS-PR from the Study of Australian School Leavers with Autism (SASLA) and the Australian Longitudinal Study of Autism in Adulthood (ALSAA). We ran a factor analysis on the scores and conducted a thematic analysis of the open-ended responses. One of the autistic advisors reviewed how we interpreted our results.What were the results of the study?: There were 92 autistic participants (46 males, 38 females, 8 nonbinary; mean age of 36 years old). On average, participants were diagnosed with autism at age 30. The factor analysis suggested three domains in the IOD-PR: Self-Acceptance and Understanding, Being Understood, and Service Access. On average, participants' scores suggested receiving an autism diagnosis was helpful for understanding and accepting themselves, but neutral for being understood by others or getting support from services.The thematic analysis identified several themes, the strongest theme was Self-Understanding, Identity, and Acceptance, where participants mostly commented on the positive new self-identity that came from their autism diagnosis. There was a Supports and Services theme that was divided into Enabled Support, Support not needed, and No or poor services. Most concerning was that many participants commented that the autism diagnosis did not enable any access to supports or that there were no appropriate supports available. There was a Valence of Response theme that was divided into Relief, Positive impact, Wish diagnosed earlier, and Negative impact. There was a Relationships theme divided into Connected with autistic community, Improves relationships, and Others lack understanding. Finally, there was a Camouflaging theme.Based on these results, the researchers are working on further revisions to the IODS-PR to make it more useful and accessible.What do these findings add to what was already known?: The adapted IODS shows promise and findings will guide further development of the tool. These early-stage findings agree with what previous research said about the impact of receiving a diagnosis of autism in adulthood.What are potential weaknesses in the study?: There are strengths and weaknesses to using a questionnaire tool to research this topic. Interview research can get a more in-depth understanding of an individual's response to the diagnosis.How will these findings help autistic adults now or in the future?: When the revised IODS is available, it could be used to evaluate support services and help clinicians understand how to help create a more positive response to diagnosis. Our findings confirm more needs to be performed about postdiagnosis supports.

GRHL2 suppresses tumor metastasis via regulation of transcriptional activity of RhoG in non-small cell lung cancer.

The transcription factor, Grainyhead-like 2 (GRHL2), is involved in wound healing, epidermal integrity, and epithelial-to-mesenchymal transition (EMT) in various biological processes; however, the biological function of GRHL2 in non-small cell lung cancer (NSCLC) is unknown. In the current study, we investigated the effect of GRHL2 on cell growth and migration in NSCLC cell lines and clinical tissues. Immunohistochemical analysis of clinical NSCLC specimens revealed that patients with high GRHL2 expression were associated with poor prognosis compared to patients with low GRHL2 expression. GRHL2 overexpression promoted cell growth and colony formation, and simultaneously suppressed cell migration in NSCLC cells. Furthermore, GRHL2 decreased the transcriptional activity of RhoG by directly binding to the RhoG promoter region. These findings confirm that GRHL2 plays an important role in regulating cell proliferation and migration in NSCLC.

Facile synthesis of red-emitting lysozyme-stabilized Ag nanoclusters.

A facile approach was developed to prepare positively charged and red-emitting lysozyme-stabilized Ag nanoclusters (Lys-AgNCs) using NaBH4 as a reducing agent at room temperature. The Lys-AgNCs can be applied in the highly selective detection of Hg²âº.

An electrochemiluminescence sensor based on a Ru(bpy)3(2+)-silica-chitosan/nanogold composite film.

Chitosan, a cationic polysaccharide containing amino and hydroxyl groups, was used to fabricate an electrochemiluminescence (ECL) sensor. In the sensor construction, a glassy carbon electrode (GCE) was first coated by a chitosan film which embedded gold nanoparticles, and then the film was modified by introducing carboxyl groups on the surface, which were used to immobilize tris(2,2'-bipyridyl)ruthenium(II) doped amino-functional silica nanoparticles (NH(2)-RuSiNPs) through amido links. The successful modification was confirmed by scanning electronic microscopy and cyclic voltammetry. A binding model between the chitosan/nanogold composite film and NH(2)-RuSiNPs was also proposed, in which the amido link was the dominant bonding, accompanied with hydrogen bond interaction. ECL studies revealed that the sensor had very good response to different concentrations of 2-(dibutylamino) ethanol. This sensor was also applied in methamphetamine determination.