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744). Models including AUCG and AUCI scores show superior fits compared with models including pre-treatment scores alone (ΔR2 = 0.196 to 0.444). IL-6 AUCG and AUCI scores are significant predictors for post-treatment SCL-GSI and BDI (β = -0.554 to 0.853), whereas IL-10 AUCG significantly predicts SCL-GSI and BDI (β = -0.449 to -0.509). Therefore, pro- and anti-inflammatory IL-6 and IL-10 levels under acute stress before therapy predict therapy outcome of female PTSD patients regarding general symptom burden and depressive symptoms. Future studies should further address the link between inflammation and therapy outcome, especially underlying mechanisms and influencing factors.Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.SLC1A5 variant (SLC1A5_var) is identified as a mitochondrial glutamine transporter in cancer cells recently. However, the role of SLC1A5_var in Parkinson's disease (PD) is completely unknown. Here, we found the significant downregulation of SLC1A5_var in astrocytes and midbrain of mice treated with MPTP/MPP+ and LPS. Importantly, overexpression of SLC1A5_var ameliorated but knockdown of SLC1A5_var exacerbated MPTP/MPP+- and LPS-induced mitochondrial dysfunction. Consequently, SLC1A5_var provided beneficial effects on PD pathology including improvement of PD-like motor symptoms and rescue of dopaminergic (DA) neuron degeneration through maintaining mitochondrial energy metabolism. Moreover, SLC1A5_var reduced astrocyte reactivity via inhibition of A1 astrocyte conversion. Further investigation demonstrated that SLC1A5_var restrained the secretion of astrocytic pro-inflammatory cytokines by blunting TLR4-mediated downstream pathways. This is the first study to prove that astrocytic SLC1A5_var inhibits neuroinflammation, and rescues the loss of DA neurons and motor symptoms involved in PD progression, which provides a novel target for PD treatment.Effective strategies for early detection of cognitive decline, if deployed on a large scale, would have individual and societal benefits. However, current detection methods are invasive or time-consuming and therefore not suitable for longitudinal monitoring of asymptomatic individuals. For example, biological markers of neuropathology associated with cognitive decline are typically collected via cerebral spinal fluid, cognitive functioning is evaluated from face-to-face assessments by experts and brain measures are obtained using expensive, non-portable equipment. Here, we describe scalable, repeatable, relatively non-invasive and comparatively inexpensive strategies for detecting the earliest markers of cognitive decline. Selleckchem Pargyline These approaches are characterized by simple data collection protocols conducted in locations outside the laboratory measurements are collected passively, by the participants themselves or by non-experts. The analysis of these data is, in contrast, often performed in a centralized location using sophisticated techniques. Recent developments allow neuropathology associated with potential cognitive decline to be accurately detected from peripheral blood samples. Advances in smartphone technology facilitate unobtrusive passive measurements of speech, fine motor movement and gait, that can be used to predict cognitive decline. Specific cognitive processes can be assayed using 'gamified' versions of standard laboratory cognitive tasks, which keep users engaged across multiple test sessions. High quality brain data can be regularly obtained, collected at-home by users themselves, using portable electroencephalography. Although these methods have great potential for addressing an important health challenge, there are barriers to be overcome. Technical obstacles include the need for standardization and interoperability across hardware and software. Societal challenges involve ensuring equity in access to new technologies, the cost of implementation and of any follow-up care, plus ethical issues.
Syngnathids are a highly derived and diverse fish clade comprising the pipefishes, pipe-horses, and seahorses. They are characterized by a plethora of iconic traits that increasingly capture the attention of biologists, including geneticists, ecologists, and developmental biologists. The current understanding of the origins of their derived body plan is, however, hampered by incomplete and limited descriptions of the early syngnathid ontogeny.
We provide a comprehensive description of the development of Nerophis ophidion, Syngnathus typhle, and Hippocampus erectus from early cleavage stages to release from the male brooding organ and beyond, including juvenile development. We comparatively describe skeletogenesis with a particular focus on dermal bony plates, the snout-like jaw morphology, and appendages.
This most comprehensive and detailed account of syngnathid development to date suggests that convergent phenotypes (e.g., reduction and loss of the caudal fins), likely arose by distinct ontogenetic means in pipefishes and seahorses. Comparison of the ontogenetic trajectories of S. typhle and H. erectus provides indications that characteristic features of the seahorse body plan result from developmental truncation. Altogether, this work provides a valuable resource and framework for future research to understand the evolution of the outlandish syngnathid morphology from a developmental perspective.
This most comprehensive and detailed account of syngnathid development to date suggests that convergent phenotypes (e.g., reduction and loss of the caudal fins), likely arose by distinct ontogenetic means in pipefishes and seahorses. Comparison of the ontogenetic trajectories of S. typhle and H. erectus provides indications that characteristic features of the seahorse body plan result from developmental truncation. Altogether, this work provides a valuable resource and framework for future research to understand the evolution of the outlandish syngnathid morphology from a developmental perspective.In this paper, we examine how young adults who are consumers of K-Pop in three culturally diverse cities (Paris, Philadelphia, and Manchester) reshape their symbolic boundaries to face social challenges. Analyzing data from 132 interviews, we show how young adults mainly confront social exclusion in Paris, fight racism in Philadelphia and deal with xenophobia in Manchester. Although K-Pop adds to the dynamics of exclusion due to being perceived as culturally foreign, our participants use K-Pop as a resource to reshape social boundaries towards new forms of inclusion. They do this by relying on K-Pop as a cultural product that promotes inclusion, and on their affiliation with the K-Pop community on a local and global level.Herein, a simple and efficient strategy that involves dual 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)/iron-catalyzed alkene perfluoroalkylvinylation by using perfluoroalkyl iodides and 2-aminonaphthalene-1,4-diones as coupling partners is demonstrated. In terms of the developed catalytic system, various styrenes and aliphatic alkenes are well-tolerated, leading to the accurate preparation of perfluoroalkyl-containing 2-aminonaphthalene-1,4-diones in excellent regioselectivity. Moreover, the protocol can be readily applied in late-stage modifications of natural products and pharmaceuticals. The title reactions are featured by easily accessible and inexpensive catalysts and substrates, broad substrate applicability, and mild reaction conditions. Mechanistic investigations reveal a tandem C-I cleavable alkylation and C-C vinylation enabled by cooperative DBU/iron catalysis.Background Collaborative care is an evidence-based multidisciplinary model shown to improve patient depression and anxiety outcomes. Although there is robust literature showing the effectiveness of collaborative care on depression and anxiety symptoms, there is little published on outcomes of collaborative care implementation or the efficacy of collaborative care compared with psychiatric referrals. Reported here is a study protocol examining a novel depression and anxiety collaborative care program in a large, integrated health care system. Methods This is a mixed methods study of the Achieving Depression and Anxiety Patient-Centered Treatment (ADAPT) program as compared to outpatient psychiatric care at Kaiser Permanente Northern California, a large, integrated health care delivery system. The ADAPT program was designed using collaborative care principles, including measurement-based care, accurate diagnosis, and population management. Eligible participants will be ≥ 18 years old with mild to moderate-severe depressive symptoms as measured by the Patient Health Questionnaire-9. Exclusion criteria include acute suicide risk and serious mental health comorbidities. Implementation is examined using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and interviews with program stakeholders. Results Pending. Conclusion Study data will help inform future collaborative care efforts while expanding the literature base. The Achieving Depression and Anxiety Patient-Centered Treatment program may improve patient outcomes and access to quality depression and/or anxiety care.The research on substance use disorders is ongoing in the quest to find anti-addiction vaccines to treat drug abuse. This article provides a systematic review of clinical trials that have been conducted on humans to evaluate the efficacy, safety, and abstinence rates of anti-addiction vaccines for different drugs, with useful results regarding cocaine and nicotine vaccines in particular; this study includes also a meta-analysis to establish the antibody-titer production following the nicotine vaccination, while a meta-analysis of cocaine vaccines was not performed due to the small number of included trials. The articles taken into consideration were published between 2002 and 2015, including searches through 2022. Overall, 13 articles were selected with 2,266 participants from different ethnic groups. The meta-analysis of nicotine vaccines showed that vaccinated groups were 50 times more likely to create specific antibodies compared to the non-vaccinated. These results demonstrated how the nicotine vaccine has good immunogenicity.
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