Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy.

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5' splice sites.

Deciphering ER stress-unfolded protein response relationship by visualizing unfolded proteins in the ER.

Despite the consensus that accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, i.e. ER stress, activates the unfolded protein response (UPR), studies under physiological and pathophysiological conditions suggest that ER stress may not always trigger the UPR, and the UPR can be activated in an ER stress-independent way.

Bronchial arterial chemoembolization with Drug-Eluting beads plus sequential chemotherapy for the treatment of stage III and IV lung squamous cell carcinoma.

Purpose: This retrospective study aimed to investigate the effectiveness and safety of bronchial arterial chemoembolization with drug-eluting beads (DEB-BACE) plus chemotherapy versus chemotherapy alone in patients with stage III and IV lung squamous cell carcinoma (LSCC) who are not appropriate candidates for radiochemotherapy.

Materials And Methods: In this retrospective analysis, we screened all adult patients undergoing either DEB-BACE plus chemotherapy or chemotherapy alone for stage III or IV LCSS at authors' center from January 2018 to August 2021. Each 21-day chemotherapy cycle consisted of intravenous injection of gemcitabine (1.

Advances in the study of IL-17 in neurological diseases and mental disorders.

Interleukin-17 (IL-17), a cytokine characteristically secreted by T helper 17 (Th17) cells, has attracted increasing attention in recent years because of its importance in the pathogenesis of many autoimmune or chronic inflammatory diseases. Recent studies have shown that neurological diseases and mental disorders are closely related to immune function, and varying degrees of immune dysregulation may disrupt normal expression of immune molecules at critical stages of neural development. Starting from relevant mechanisms affecting immune regulation, this article reviews the research progress of IL-17 in a selected group of neurological diseases and mental disorders (autism spectrum disorder, Alzheimer's disease, epilepsy, and depression) from the perspective of neuroinflammation and the microbiota-gut-brain axis, summarizes the commonalities, and provides a prospective outlook of target application in disease treatment.

Expression of Concern: Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery.

Expression of Concern for 'Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery' by Jianxin Liu , , 2018, , 2838-2849, https://doi.org/10.1039/C8BM00726H.

TREM-1 as a potential prognostic biomarker associated with immune infiltration in clear cell renal cell carcinoma.

Background: The tumor immune microenvironment plays a crucial role in the efficacy of various therapeutics. However, their correlation is not yet completely understood in Clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the potential of TREM-1 as a potential novel biomarker for ccRCC.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism.

Purpose: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS.

Multistep sequence-controlled supramolecular polymerization by the combination of multiple self-assembly motifs.

The precise sequence control of polymer chain is an important research topic of polymer chemistry. Although some methods such as iterative synthesis and supramolecular polymerization have been developed to fabricate sequence-controllable polymer, it is still a great challenge to consecutively prepare multiple supramolecular polymers with different sequence structures. In this work, through the reasonable utilization of assembly motifs, we integrated multiple host-guest recognitions and metal coordination interactions to prepare different sequence-controlled supramolecular polymers by a multistep assembly strategy.

HMGB1 in nervous system diseases: A common biomarker and potential therapeutic target.

High-mobility group box-1 (HMGB1) is a nuclear protein associated with early inflammatory changes upon extracellular secretion expressed in various cells, including neurons and microglia. With the progress of research, neuroinflammation is believed to be involved in the pathogenesis of neurological diseases such as Parkinson's, epilepsy, and autism. As a key promoter of neuroinflammation, HMGB1 is thought to be involved in the pathogenesis of Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, and amyotrophic lateral sclerosis.

Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a mice with spontaneously diabetic Ins2 (Akita) mice.

Supramolecular polymer gels: from construction methods to functionality.

Supramolecular polymer gels (SPGs) are precisely designed gels brought together by noncovalent interactions to form three-dimensional network structures of polymers. SPGs combine the merits of supramolecular polymers and gels, such as stimuli-responsiveness, self-healing, and self-adaptation, which endows SPGs with potential application value in the fields of biomaterials, Recently, much effort has been made to design new SPGs and related materials with high performance. Herein, we review the research endeavor and future directions of SPGs depending on the construction methods, topological structures, stimuli-responsiveness, and functionality.

Crown Ether-Based Supramolecular Polymers: From Synthesis to Self-Assembly.

Supramolecular polymers not only possess many advantages of traditional polymers, but also have many unique characteristics. Supramolecular polymers can be constructed by self-assembly of various noncovalent interactions. Host-guest interaction, as one important type of noncovalent interactions, has been widely applied to construct supramolecular polymers.

Dopamine receptor D2 on CD4 T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4 T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5.

Combination LSD1 and HOTAIR-EZH2 inhibition disrupts cell cycle processes and induces apoptosis in glioblastoma cells.

Glioblastoma (GBM) is the most common primary central nervous system tumor and has a poor prognosis, with a median survival time of only 14 months from diagnosis. Abnormally expressed long noncoding RNAs (lncRNAs) are important epigenetic regulators of chromatin modification and gene expression regulation in tumors, including GBM. We previously showed that the lncRNA HOTAIR is related to the cell cycle progression and can be used as an independent predictor in GBM.

The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas.

Background: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood.

Methods: In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα.

11p11.12p12 duplication in a family with intellectual disability and craniofacial anomalies.

Background: Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder.

Alterations in the gut microbiota may influence gastrointestinal (GI) dysbiosis frequently reported in individuals with autism spectrum disorder (ASD). In this study, we sequenced the bacterial 16S rRNA gene to evaluate changes in fecal microbiota between 48 children with ASD and 48 healthy children in China. At the phylum level, the number of Firmicutes, Proteobacteria, and Verrucomicrobia decreased in children with ASD, while the Bacteroidetes/Firmicutes was significantly higher in autistic children due to enrichment of Bacteroidetes.

Ultrasound and Clinical Characteristics of False-negative Results in Mammography Screening of Dense Breasts.

Objective: We analyzed the clinical and ultrasound characteristics associated with false-negative mammography results in women with dense breasts.

Materials And Methods: The present study included 191 women (mean age, 54.47 ± 11.

Protein kinase C-ε contributes to a chronic inhibitory effect of IL-1β on voltage-gated sodium channels in mice with febrile seizure.

This study aimed to understand the role of Interleukin-1β in mouse febrile seizures. To investigate the chronic effects of raised Interleukin-1β on seizures, the sodium currents of hippocampal neurons were recorded by whole-cell voltage clamp. Interleukin-1β inhibited sodium currents in mouse hippocampal neurons and verified that protein kinase C epsilon contributed to the effect of Interleukin-1β exposure.

Human epididymis protein 4 (HE4) protects against cystic pulmonary fibrosis associated-inflammation through inhibition of NF-κB and MAPK singnaling.

Background: Cystic pulmonary fibrosis (CF) affects mostly the lung of the newborns. Chronic infection and inflammation become the major causes of morbidity and mortality in CF. However, the underlying molecular mechanisms causing CF still remain unclear.

Inhibition of microRNA-34a Suppresses Epileptiform Discharges Through Regulating Notch Signaling and Apoptosis in Cultured Hippocampal Neurons.

Epilepsy is characterized by recurrent unprovoked seizures and some seizures can cause neuronal apoptosis, which is possible to make contributions to the epilepsy phenotype, impairments in cognitive function or even epileptogenesis. Moreover, many studies have indicated that microRNA-34a (miRNA-34a) is involved in apoptosis through regulating Notch signaling. However, whether miRNA-34a participates in neuronal apoptosis after seizures remain unclear.

Pillararene-based supramolecular polymers.

Pillararenes, as a new type of macrocyclic hosts, possess columnar structures and electron-rich cavities. Pillararenes not only recognize suitable cations, but also bind many neutral molecules. Due to the easy modification of pillararenes, various functional groups can be conveniently attached to the rim of pillararenes to provide suitable interaction sites, and the modified pillararenes even bind anionic guests.

Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery.

Theranostics is a new trend in the tumor research field, which involves the integration of diagnostic and therapeutic functions using imageable nanoparticles coupled with therapeutic drugs. Imaging-guided targeted delivery of therapeutics and diagnostics using nanocarriers hold great promise to minimize the side effects of conventional chemotherapy. Ultrasound microbubbles have been employed as theranostic agents over the last decade, which provide both real-time dynamic imaging for diagnosis and precise control for targeted tumor therapy.

The Therapeutic Effect of ICAM-1-Overexpressing Mesenchymal Stem Cells on Acute Graft-Versus-Host Disease.

Background/aims: Mesenchymal stem cells (MSCs) do not readily migrate to appropriate sites, and this creates a major obstacle for their use in the treatment of graft-versus-host disease (GVHD). Intercellular adhesion molecule-1 (ICAM-1) can guide the homing of various immune cells to the proper anatomical location within secondary lymphoid organs (SLOs), which are the major niches for generating immune responses or tolerance. MSCs rarely migrate to SLOs after intravenous infusion, and are constitutively low expression of ICAM-1.

A Color-Tunable Fluorescent Supramolecular Hyperbranched Polymer Constructed by Pillar[5]arene-Based Host-Guest Recognition and Metal Ion Coordination Interaction.

Fluorescent supramolecular polymers are an important kind of smart material. In this work, a new fluorescent supramolecular hyperbranched polymer (FSHP) is constructed by orthogonal self-assembly: pillararene-based host-guest interaction and metal ion complexation interaction. The FSHP exhibits concentration-controllable fluorescence emissions.