bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-assembly of DNA nanostructure containing cell-specific aptamer as a precise drug delivery system for cancer therapy in non-small cell lung cancer
Authors: Wang Ning , Yu Chang , Xu Tingting , Yao Dan , Zhu Lingye , Shen Zhifa , Huang Xiaoying 
Published: November 2022

Abstract
Background
As the most common subtype in lung cancer, the precise and efficient treatment for non-small cell lung cancer (NSCLC) remains an outstanding challenge owing to early metastasis and poor prognosis. Chemotherapy, the most commonly used treatment modality, is a difficult choice for many cancer patients due to insufficient drug accumulation in tumor sites and severe systemic side-effects. In this study, we constructed a cell-specific aptamer-modified DNA nanostructure (Apt-NS) as a targeting drug delivery system achieving the precision therapy for lung cancer.

Methods
The synthesis of DNA nanostructure and its stability were evaluated using gel electrophoresis. The targeting properties and internalization mechanism were investigated via flow cytometry and confocal analyses. Drug loading, release, and targeted drug delivery were determined by fluorescence detection, Zeta potentials assay, and confocal imaging. CCK8 assays, colony formation, cell apoptosis, metastasis analyses and in vivo experiments were conducted to assess the biological functions of DNA nanostructure.

Results
Self-assembled DNA nanoparticles (Apt-NS) had excellent stability to serum and DNase I and the ability to specifically recognize A549 cells. Upon specific binding, the drug-loaded nanoparticles (Apt-NS-DOX) were internalized into target cells by clathrin-mediated endocytosis. Subsequently, DOX could be released from Apt-NS-DOX based on the degradation of the lysosome. Apt-NS-DOX exerted significant suppression of cell proliferation, invasion and migration, and also enhanced cell apoptosis due to the excellent performance of drug delivery and intracellular release, while maintaining a superior biosafety. In addition, the antitumor effects of Apt-NS-DOX were further confirmed using in vivo models.

Conclusions
Our study provided cell-specific aptamer-modified DNA nanostructures as a drug-delivery system targeting A549 cells, which could precisely and efficiently transport chemotherapeutic drug into tumor cells, exerting enhanced antineoplastic efficacy. These findings highlight that DNA nanostructure serving as an ideal drug delivery system in cancer treatment appears great promise in biomedical applications.
Polymeric nanomedicines for the treatment of hepatic diseases
Authors: Luo Feixiang , Yu Ying , Li Mingqian , Chen Yuguo , Zhang Peng , Xiao Chunsheng , Lv Guoyue 
Published: November 2022

AbstractThe liver is an important organ in the human body and performs many functions, such as digestion, detoxification, metabolism, immune responses, and vitamin and mineral storage. Therefore, disorders of liver functions triggered by various hepatic diseases, including hepatitis B virus infection, nonalcoholic steatohepatitis, hepatic fibrosis, hepatocellular carcinoma, and transplant rejection, significantly threaten human health worldwide. Polymer-based nanomedicines, which can be easily engineered with ideal physicochemical characteristics and functions, have considerable merits, including contributions to improved therapeutic outcomes and reduced adverse effects of drugs, in the treatment of hepatic diseases compared to traditional therapeutic agents. This review describes liver anatomy and function, and liver targeting strategies, hepatic disease treatment applications and intrahepatic fates of polymeric nanomedicines. The challenges and outlooks of hepatic disease treatment with polymeric nanomedicines are also discussed.
Music festival drug checking: evaluation of an Australian pilot program
Authors: Olsen Anna , Wong Gabriel , McDonald David 
Published: November 2022

Abstract
Background
This paper explores the feasibility of delivering a music festival-based drug checking service in Australia, evaluating service design and stakeholder acceptability.

Methods
Questionnaire and interview data were collected from adult service users and key stakeholders. A mixed methods approach was used to analyse the data on implementation, impact and acceptability.

Results
The trial service tested 170 substances with more than 230 patrons (including individuals who attended in groups). Adult service users had an average age of 21 years. Voluntary participation in the evaluation resulted in 158 participants completing the pre-service questionnaire, most of whom also completed the post-service (147 participants). Eleven in-depth qualitative interviews were conducted with patrons in the weeks following the drug checking. Concordance between what the patron expected the drug to be and drug checking results occurred in 88 per cent (n = 139) of the sample. Evaluation results show that the experience of testing and the accompanying harm reduction brief interventions positively impacted on patrons’ self-reported drug harm reduction knowledge, trust of health providers and stated drug use intentions. The service was received positively by service users.

Conclusion
This is the first independent evaluation of a pilot drug checking service in Australia. Consideration of operational feasibility and self-reported behavioural change suggests that the program was successful, although communication about the interpretation of drug checking results could be improved. Future studies should develop strategies for follow-up and consider the applicability of behavioural change theory.
Juvenile idiopathic arthritis polygenic risk scores are associated with cardiovascular phenotypes in early adulthood: a phenome-wide association study
Authors: Clarke Sarah L. N. , Jones Hannah J. , Sharp Gemma C. , Easey Kayleigh E. , Hughes Alun D. , Ramanan Athimalaipet V. , Relton Caroline L. 
Published: November 2022

Abstract
Background
There is growing concern about the long-term cardiovascular health of patients with juvenile idiopathic arthritis (JIA). In this study we assessed the association between JIA polygenic risk and cardiovascular phenotypes (cardiovascular risk factors, early atherosclerosis/arteriosclerosis markers, and cardiac structure and function measures) early in life.

Methods
JIA polygenic risk scores (PRSs) were constructed for 2,815 participants from the Avon Longitudinal Study of Parents and Children, using the single nucleotide polymorphism (SNP) weights from the most recent JIA genome wide association study. The association between JIA PRSs and cardiovascular phenotypes at age 24 years was assessed using linear and logistic regression. For outcomes with strong evidence of association, further analysis was undertaken to examine how early in life (from age seven onwards) these associations manifest.

Results
The JIA PRS was associated with diastolic blood pressure (β 0.062, 95% CI 0.026 to 0.099, P = 0.001), insulin (β 0.050, 95% CI 0.011 to 0.090, P = 0.013), insulin resistance index (HOMA2_IR, β 0.054, 95% CI 0.014 to 0.095, P = 0.009), log hsCRP (β 0.053, 95% CI 0.011 to 0.095, P = 0.014), waist circumference (β 0.041, 95% CI 0.007 to 0.075, P = 0.017), fat mass index (β 0.049, 95% CI 0.016 to 0.083, P = 0.004) and body mass index (β 0.046, 95% CI 0.011 to 0.081, P = 0.010). For anthropometric measures and diastolic blood pressure, there was suggestive evidence of association with JIA PRS from age seven years. The findings were consistent across multiple sensitivity analyses.

Conclusions
Genetic liability to JIA is associated with multiple cardiovascular risk factors, supporting the hypothesis of increased cardiovascular risk in JIA. Our findings suggest that cardiovascular risk is a core feature of JIA, rather than secondary to the disease activity/treatment, and that cardiovascular risk counselling should form part of patient care.
Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma
Authors: Pachocki Casper J. , Hol Elly M. 
Published: November 2022

AbstractDiffuse midline glioma (DMG), formerly called diffuse intrinsic pontine glioma (DIPG), is a high-grade malignant pediatric brain tumor with a near-zero survival rate. To date, only radiation therapy provides marginal survival benefit; however, the median survival time remains less than a year. Historically, the infiltrative nature and sensitive location of the tumor rendered surgical removal and biopsies difficult and subsequently resulted in limited knowledge of the disease, as only post-mortem tissue was available. Therefore, clinical decision-making was based upon experience with the more frequent and histologically similar adult glioblastoma (GBM). Recent advances in tissue acquisition and molecular profiling revealed that DMG and GBM are distinct disease entities, with separate tissue characteristics and genetic profiles. DMG is characterized by heterogeneous tumor tissue often paired with an intact blood–brain barrier, possibly explaining its resistance to chemotherapy. Additional profiling shed a light on the origin of the disease and the influence of several mutations such as a highly recurring K27M mutation in histone H3 on its tumorigenesis. Furthermore, early evidence suggests that DMG has a unique immune microenvironment, characterized by low levels of immune cell infiltration, inflammation, and immunosuppression that may impact disease development and outcome. Within the tumor microenvironment of GBM, tumor-associated microglia/macrophages (TAMs) play a large role in tumor development. Interestingly, TAMs in DMG display distinct features and have low immune activation in comparison to other pediatric gliomas. Although TAMs have been investigated substantially in GBM over the last years, this has not been the case for DMG due to the lack of tissue for research. Bit by bit, studies are exploring the TAM–glioma crosstalk to identify what factors within the DMG microenvironment play a role in the recruitment and polarization of TAMs. Although more research into the immune microenvironment is warranted, there is evidence that targeting or stimulating TAMs and their factors provide a potential treatment option for DMG. In this review, we provide insight into the current status of DMG research, assess the knowledge of the immune microenvironment in DMG and GBM, and present recent findings and therapeutic opportunities surrounding the TAM–glioma crosstalk.
Constitutively active microglial populations limit anorexia induced by the food contaminant deoxynivalenol
Authors: Gaige Stéphanie , Barbouche Rym , Barbot Manon , Boularand Sarah , Dallaporta Michel , Abysique Anne , Troadec Jean-Denis 
Published: November 2022

AbstractMicroglia are involved in neuroinflammatory processes during diverse pathophysiological conditions. To date, the possible contribution of these cells to deoxynivalenol (DON)-induced brain inflammation and anorexia has not yet been evaluated. DON, one of the most abundant trichothecenes found in cereals, has been implicated in mycotoxicosis in both humans and farm animals. DON-induced toxicity is characterized by reduced food intake, weight gain, and immunological effects. We previously showed that exposure to DON induces an inflammatory response within the hypothalamus and dorsal vagal complex (DVC) which contributes to DON-induced anorexia. Here, in response to anorectic DON doses, we reported microglial activation within two circumventricular organs (CVOs), the area postrema (AP) and median eminence (ME) located in the DVC and the hypothalamus, respectively. Interestingly, this microglial activation was observed while DON-induced anorexia was ongoing (i.e., 3 and 6 h after DON administration). Next, we took advantage of pharmacological microglia deletion using PLX3397, a colony-stimulating factor 1 receptor (CSF1R)-inhibitor. Surprisingly, microglia-depleted mice exhibited an increased sensitivity to DON since non-anorectic DON doses reduced food intake in PLX3397-treated mice. Moreover, low DON doses induced c-Fos expression within feeding behavior-associated structures in PLX3397-treated mice but not in control mice. In parallel, we have highlighted heterogeneity in the phenotype of microglial cells present in and around the AP and ME of control animals. In these areas, microglial subpopulations expressed IBA1, TMEM119, CD11b and CD68 to varying degrees. In addition, a CD68 positive subpopulation showed, under resting conditions, a noticeable phagocytotic/endocytotic activity. We observed that DON strongly reduced CD68 in the hypothalamus and DVC. Finally, inactivation of constitutively active microglia by intraperitoneal administration of minocycline resulted in anorexia with a DON dose ineffective in control mice. Taken together, these results strongly suggest that various populations of microglial cells residing in and around the CVOs are maintained in a functionally active state even under physiological conditions. We propose that these microglial cell populations are attempting to protect the brain parenchyma from hazardous molecules coming from the blood. This study could contribute to a better understanding of how microglia respond to environmental contaminants.
Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury
Authors: Zhou Chao , Sun Ping , Hamblin Milton H. , Yin Ke-Jie 
Published: November 2022

Abstract
Background
The long-term functional recovery of traumatic brain injury (TBI) is hampered by pathological events, such as parenchymal neuroinflammation, neuronal death, and white matter injury. Krüppel-like transcription factor 11 (KLF 11) belongs to the zinc finger family of transcription factors and actively participates in various pathophysiological processes in neurological disorders. Up to now, the role and molecular mechanisms of KLF11 in regulating the pathogenesis of brain trauma is poorly understood.

Methods
KLF11 knockout (KO) and wild-type (WT) mice were subjected to experimental TBI, and sensorimotor and cognitive functions were evaluated by rotarod, adhesive tape removal, foot fault, water maze, and passive avoidance tests. Brain tissue loss/neuronal death was examined by MAP2 and NeuN immunostaining, and Cresyl violet staining. White matter injury was assessed by Luxol fast blue staining, and also MBP/SMI32 and Caspr/Nav1.6 immunostaining. Activation of cerebral glial cells and infiltration of blood-borne immune cells were detected by GFAP, Iba-1/CD16/32, Iba-1/CD206, Ly-6B, and F4/80 immunostaining. Brian parenchymal inflammatory cytokines were measured with inflammatory array kits.

Results
Genetic deletion of KLF11 worsened brain trauma-induced sensorimotor and cognitive deficits, brain tissue loss and neuronal death, and white matter injury in mice. KLF11 genetic deficiency in mice also accelerated post-trauma astrocytic activation, promoted microglial polarization to a pro-inflammatory phenotype, and increased the infiltration of peripheral neutrophils and macrophages into the brain parenchyma. Mechanistically, loss-of-KLF11 function was found to directly increase the expression of pro-inflammatory cytokines in the brains of TBI mice.

Conclusion
KLF11 acts as a novel protective factor in TBI. KLF11 genetic deficiency in mice aggravated the neuroinflammatory responses, grey and white matter injury, and impaired long-term sensorimotor and cognitive recovery. Elucidating the functional importance of KLF11 in TBI may lead us to discover novel pharmacological targets for the development of effective therapies against brain trauma.
The neuropeptide PACAP alleviates T. gondii infection-induced neuroinflammation and neuronal impairment
Authors: Figueiredo Caio Andreeta , Düsedau Henning Peter , Steffen Johannes , Ehrentraut Stefanie , Dunay Miklos P. , Toth Gabor , Reglödi Dora , Heimesaat Markus M. , Dunay Ildiko Rita 
Published: November 2022

AbstractBackgroundCerebral infection with the protozoanToxoplasma gondii(T. gondii) is responsible for inflammation of the central nervous system (CNS) contributing to subtle neuronal alterations. Albeit essential for brain parasite control, continuous microglia activation and recruitment of peripheral immune cells entail distinct neuronal impairment upon infection-induced neuroinflammation. PACAP is an endogenous neuropeptide known to inhibit inflammation and promote neuronal survival. Since PACAP is actively transported into the CNS, we aimed to assess the impact of PACAP on theT. gondii-induced neuroinflammation and subsequent effects on neuronal homeostasis.MethodsExogenous PACAP was administered intraperitoneally in the chronic stage ofT. gondiiinfection, and brains were isolated for histopathological analysis and determination of pathogen levels. Immune cells from the brain, blood, and spleen were analyzed by flow cytometry, and the further production of inflammatory mediators was investigated by intracellular protein staining as well as expression levels by RT-qPCR. Neuronal and synaptic alterations were assessed on the transcriptional and protein level, focusing on neurotrophins, neurotrophin-receptors and signature synaptic markers.ResultsHere, we reveal that PACAP administration reduced the inflammatory foci and the number of apoptotic cells in the brain parenchyma and restrained the activation of microglia and recruitment of monocytes. The neuropeptide reduced the expression of inflammatory mediators such as IFN-γ, IL-6, iNOS, and IL-1β. Moreover, PACAP diminished IFN-γ production by recruited CD4+ T cells in the CNS. Importantly, PACAP promoted neuronal health via increased expression of the neurotrophin BDNF and reduction of p75NTR, a receptor related to neuronal cell death. In addition, PACAP administration was associated with increased expression of transporters involved in glutamatergic and GABAergic signaling that are particularly affected during cerebral toxoplasmosis.ConclusionsTogether, our findings unravel the beneficial effects of exogenous PACAP treatment upon infection-induced neuroinflammation, highlighting the potential implication of neuropeptides to promote neuronal survival and minimize synaptic prejudice.
The envelope proteins from SARS-CoV-2 and SARS-CoV potently reduce the infectivity of human immunodeficiency virus type 1 (HIV-1)
Authors: Henke Wyatt , Waisner Hope , Arachchige Sachith Polpitiya , Kalamvoki Maria , Stephens Edward 
Published: November 2022

Abstract
Background
Viroporins are virally encoded ion channels involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 275 amino acid protein known as Orf3a. Here, we compared the replication of HIV-1 in the presence of four different β-coronavirus E proteins.

Results
We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, neither reverse transcription nor mRNA synthesis was involved in the restriction. We also show that all four E proteins caused phosphorylation of eIF2-α at similar levels and that lipidation of LC3-I could not account for the differences in restriction. However, the level of caspase 3 activity in transfected cells correlated with HIV-1 restriction in cells. Finally, we show that unlike the Vpu protein of HIV-1, the four E proteins did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2).

Conclusions
The results of this study indicate that while viroporins from homologous viruses can enhance virus release, we show that a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and release of infectious virus.
Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity
Authors: Dai Wei , Zhong Aifang , Qiao Qinghua , Wu Jian , Li Weiwei , Wu Qiuyue , Zhou Hongjian , Qin Shijie , Jiang Weijun , Zhang Jing , Xia Xinyi 
Published: November 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated.

Methods
The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients.

Results
In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases.

Conclusion
A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.
Right brain-to-right brain psychotherapy: recent scientific and clinical advances
Authors: Schore Allan 
Published: November 2022

AbstractThis article overviews my recent acceptance of a Lifetime Achievement Award from Sapienza University of Rome, in which I discussed three decades of my work on the right brain in development, psychopathogenesis, and psychotherapy. In the following, I offer current brain laterality and hemispheric asymmetry research indicating that right brain emotional and relational processes operate beneath conscious awareness not only in early human development, but over the lifespan. I discuss recent interdisciplinary studies on the central role of ultrarapid right brain-to-right brain intersubjective communications of face, voice, and gesture and the implicit regulation of emotion in nonverbal attachment dynamics. Special emphasis is on the fundamental psychobiological process of interpersonal synchrony, and on the evolutionary mechanism of attachment, the interactive regulation of biological synchrony within and between organisms. I then present some clinical applications, suggesting that effective therapeutic work with “primitive” nonverbal emotional attachment dynamics focuses not on conscious verbal insight but on the formation of an unconscious emotion-communicating and regulating bond within the therapeutic relationship. Lastly, I review recent hyperscanning research of the patient’s and therapist’s brains during a face-to-face, emotionally focused psychotherapy session that supports the right brain-to-right brain communication model. I end suggesting that the right brain is dominant in both short-term symptom-reducing and long-term growth-promoting deep psychotherapy.