Nimodipine ameliorates liver fibrosis via reshaping liver immune microenvironment in TAA-induced in mice.

Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4+T and CD8+T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4+/CD8+T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro. Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.

Plasma GPI and PGD are associated with vascular normalization and may serve as novel prognostic biomarkers for lung adenocarcinoma: Multi-omics and multi-dimensional analysis.

The aim of this study was to explore potentially novel plasma protein biomarkers for lung adenocarcinoma (LUAD). A plasma proteomics analysis was carried and candidate protein biomarkers were validated in 102 LUAD cases and 102 matched healthy controls. The same LUAD tumor tissues were detected to explore the correlation between the expression of candidate proteins in tissues and plasma and vascular normalization. A LUAD active metastasis mice model was constructed to explore the role of candidate proteins for lung metastasis. GPI and PGD were verified to be upregulated in plasma from LUAD patients, and the expression of GPI in tumor tissue was positively correlated with the expression of GPI in plasma and negatively correlated with the normalization of tumor blood vessels. Meanwhile, a negative correlation between the expression of GPI and PGD in plasma and tumor vascular normalization was discovered. In the LUAD active metastasis model, the lowest levels of vascular normalization and the highest expression of GPI and PGD were found in mice with lung metastases. This study found that GPI and PGD may be potential plasma biomarkers for LUAD, and monitoring those may infer the risk of metastasis and malignancy of the tumor. SIGNIFICANT: We identified GPI and PGD as potential novel diagnostic and prognostic biomarkers for LUAD. PGD and GPI can be used as diagnostic biomarkers in combination with other available strategies to assist in the screening and diagnosis of LUAD, and as prognostic biomarkers aid in predict the risk of tumor metastasis and malignancy in patients with LUAD.

Therapeutic sleep deprivation for major depressive disorder: A randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.

Ultra-stretchable, adhesive, fatigue resistance, and anti-freezing conductive hydrogel based on gelatin/guar gum and liquid metal for dual-sensory flexible sensor and all-in-one supercapacitors.

Benefiting from the tissue-like mechanical properties, conductive hydrogels have emerged as a promising candidate for manufacturing wearable electronics. However, the high water content within hydrogels will inevitably freeze at subzero temperature, causing a degradation or loss of functionality, which severely prevent their practical application in wearable electronics. Herein, an anti-freezing hydrogel integrating high conductivity, superior stretchability, and robust adhesion was fabricated by dissolving choline chloride and gallium in gelatin/guar gum network using borax as the cross-linker. Based on the synergistic effect of dynamic borate ester bonds and hydrogen bonds, the hydrogel exhibited rapid self-healing property and excellent fatigue resistance. Profiting from these fascinating characteristics, the hydrogel was assembled as strain sensor to precisely detect various human activities with high strain sensitivity and fast response time. Meanwhile, the hydrogel was demonstrated high sensitivity and rapid response to temperature, which can be used as thermal sensor to monitor temperature. Moreover, the conductive hydrogel was encapsulated into supercapacitors with high areal capacitance and favorable cycle stability. Importantly, the flexible sensor and supercapacitors still maintain stable sensing performance and good electrochemical performance even at subzero temperature. Therefore, our work broaden hydrogels application in intelligent wearable devices and energy storage in extreme environments.

Self-management behavior strategy based on behavioral economics in patients with hypertension: a scoping review.

Hypertensive patients often do not make the most favorable choices and behaviors for managing disease. Behavioral economics strategies offer new ideas for guiding patients toward health behavior. The scoping review aimed to summarize behavioral economics strategies designed to improve hypertension self-management behaviors. A literature search was conducted in September 2022 using the following electronic databases: Embase, Medline, CINAHL, PsycINFO, Web of Science, Cochrane Library, CNKI, Wan Fang Database for Chinese Periodicals, and CBM-SinoMed. We screened the literature for experimental studies written in Chinese or English reporting on BE strategies designed to improve self-management behavior in hypertension. We searched 17 820 records and included 18 articles in the final scoping review. We performed qualitative synthesis by the categories of choice architecture. The most common BE strategies were those targeting decision information and decision assistance, such as changing the presentation of information, making information visible, and providing reminders for actions. Most strategies targeted BP, diet, medication adherence, and physical activity behavior. Ten out of 18 studies reported statistically significant improvement in self-management behavior. Further research on BE strategies should focus on addressing the challenges, including changing the decision structure, encompassing a more comprehensive range of target behaviors, and examining the long-term effects of BE strategies.

Self-management of hypertension is a long-term effort, but people often make bounded rational decisions and act in ways that deviate from health goals. Behavioral Economics (BE) strategies make small changes in the decision-making environment to alter choices, steering individuals' behavior consistent with their goals or preferences. We summarized the BE strategies to improve self-management behavior in hypertension and described the study results using the categories of choice architecture. We found that the most widely used BE strategy is changing the presentation of information in the decision-making environment. Most BE strategies positively affect the target behaviors, which have the potential of BE strategies to enhance self-management behavior for hypertension. Further research is needed to identify the origins of these strategies, modify decision-making structures, and incorporate a broader range of health behaviors to showcase the practicality and sustainability of implementing BE strategies.

OCTN2- and ATB0,+-targeted nanoemulsions for improving ocular drug delivery.

Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases.

Copy number gain of FAM131B-AS2 promotes the progression of glioblastoma by mitigating replication stress.

BACKGROUND: Glioblastoma (GBM) is characterized by chromosome 7 copy number gains, notably 7q34, potentially contributing to therapeutic resistance, yet the underlying oncogenes have not been fully characterized. Pertinently, the significance of long noncoding RNAs (lncRNAs) in this context has gained attention, necessitating further exploration. METHODS: FAM131B-AS2 was quantified in GBM samples and cells using qPCR. Overexpression and knockdown of FAM131B-AS2 in GBM cells were used to study its functions in vivo and in vitro. The mechanisms of FAM131B-AS2 were studied using RNA-seq, qPCR, Western blotting, RNA pull-down, coimmunoprecipitation assays, and mass spectrometry analysis. The phenotypic changes that resulted from FAM131B-AS2 variation were evaluated through CCK8 assay, EdU assay, comet assay, and immunofluorescence. RESULTS: Our analysis of 149 primary GBM patients identified FAM131B-AS2, a lncRNA located in the 7q34 region, whose upregulation predicts poor survival. Mechanistically, FAM131B-AS2 is a crucial regulator of the replication stress response, stabilizing replication protein A1 through recruitment of ubiquitin-specific peptidase 7 and activating the ataxia telangiectasia and rad3-related protein kinase pathway to protect single-stranded DNA from breakage. Furthermore, FAM131B-AS2 overexpression inhibited CD8+ T-cell infiltration, while FAM131B-AS2 inhibition activated the cGAS-STING pathway, increasing lymphocyte infiltration and improving the response to immune checkpoint inhibitors. CONCLUSIONS: FAM131B-AS2 emerges as a promising indicator for adjuvant therapy response and could also be a viable candidate for combined immunotherapies against GBMs.

Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells.

Neuronal activity can drive progression of high-grade glioma by mediating mitogen production and neuron-glioma synaptic communications. Glioma stem cells (GSC) also play a significant role in progression, therapy resistance, and recurrence in glioma, which implicates potential cross-talk between neuronal activity and GSC biology. Here, we manipulated neuronal activity using chemogenetics in vitro and in vivo to study how it influences GSCs. Neuronal activity supported glioblastoma (GBM) progression and radioresistance through exosome-induced proneural-to-mesenchymal transition (PMT) of GSCs. Molecularly, neuronal activation led to elevated miR-184-3p in neuron-derived exosomes that were taken up by GSCs and reduced the mRNA N6-methyladenosine (m6A) levels by inhibiting RBM15 expression. RBM15 deficiency decreased m6A modification of DLG3 mRNA and subsequently induced GSC PMT by activating the STAT3 pathway. Loss of miR-184-3p in cortical neurons reduced GSC xenograft growth, even when neurons were activated. Levetiracetam, an antiepileptic drug, reduced the neuronal production of miR-184-3p-enriched exosomes, inhibited GSC PMT, and increased radiosensitivity of tumors to prolong survival in xenograft mouse models. Together, these findings indicate that exosomes derived from active neurons promote GBM progression and radioresistance by inducing PMT of GSCs. SIGNIFICANCE: Active neurons secrete exosomes enriched with miR-184-3p that promote glioblastoma progression and radioresistance by driving the proneural-to-mesenchymal transition in glioma stem cells, which can be reversed by antiseizure medication levetiracetam.

Hypoxia-Induced Neuronal Activity in Glioma Patients Polarizes Microglia by Potentiating RNA m6A Demethylation.

PURPOSE: Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. EXPERIMENTAL DESIGN: By applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. RESULTS: We demonstrate that hypoxia drove glioma stem cells (GSC) to produce higher levels of glutamate, which activated local neurons. Neuronal activity promoted GBM progression by facilitating microglial M2 polarization through enriching miR-200c-3p in neuron-derived exosomes, which decreased the expression of the m6A writer zinc finger CCCH-type containing 13 (ZC3H13) in microglia, impairing methylation of dual specificity phosphatase 9 (DUSP9) mRNA. Downregulation of DUSP9 promoted ERK pathway activation, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted microglial M2 polarization whereas cortical neuronal inhibition decreased microglial M2 polarization in GBM xenografts. miR-200c-3p knockdown in cortical neurons impaired microglial M2 polarization and GBM xenograft growth, even when cortical neurons were activated. Treatment with the anti-seizure medication levetiracetam impaired neuronal activation and subsequently reduced neuron-mediated microglial M2 polarization. CONCLUSIONS: These findings indicated that hypoxic GSC-induced neuron activation promotes GBM progression by polarizing microglia via the exosomal miR-200c-3p/ZC3H13/DUSP9/p-ERK pathway. Levetiracetam, an antiepileptic drug, blocks the abnormal activation of neurons in GBM and impairs activity-dependent GBM progression. See related commentary by Cui et al., p. 1073.

The potential health effects associated with electronic-cigarette.

A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits.

Multifunctional Conductive Double-Network Hydrogel Sensors for Multiscale Motion Detection and Temperature Monitoring.

As typical soft materials, hydrogels have demonstrated great potential for the fabrication of flexible sensors due to their highly compatible elastic modulus with human skin, prominent flexibility, and biocompatible three-dimensional network structure. However, the practical application of wearable hydrogel sensors is significantly constrained because of weak adhesion, limited stretchability, and poor self-healing properties of traditional hydrogels. Herein, a multifunctional sodium hyaluronate (SH)/borax (B)/gelatin (G) double-cross-linked conductive hydrogel (SBG) was designed and constructed through a simple one-pot blending strategy with SH and gelatin as the gel matrix and borax as the dynamic cross-linker. The obtained SBG hydrogels exhibited a moderate tensile strength of 25.3 kPa at a large elongation of 760%, high interfacial toughness (106.5 kJ m-3), strong adhesion (28 kPa to paper), and satisfactory conductivity (224.5 mS/m). In particular, the dynamic cross-linking between SH, gelatin, and borax via borate ester bonds and hydrogen bonds between SH and gelatin chain endowed the SBG hydrogels with good fatigue resistance (>300 cycles), rapid self-healing performance (HE (healing efficiency) ∼97.03%), and excellent repeatable adhesion. The flexible wearable sensor assembled with SBG hydrogels demonstrated desirable strain sensing performance with a competitive gauge factor and exceptional stability, which enabled it to detect and distinguish various multiscale human motions and physiological signals. Furthermore, the flexible sensor is capable of precisely perceiving temperature variation with a high thermal sensitivity (1.685% °C-1). As a result, the wearable sensor displayed dual sensory performance for temperature and strain deformation. It is envisioned that the integration of strain sensors and thermal sensors provide a novel and convenient strategy for the next generation of multisensory wearable electronics and lay a solid foundation for their application in electronic skin and soft actuators.

Cu/SiO2 synthesized with HKUST-1 as precursor: high ratio of Cu+/(Cu+ + Cu0) and rich oxygen defects for efficient catalytic hydrogenation of furfural to 2-methyl furan.

Cu/SiO2 is one of the most promising catalysts for the furfural (FF) hydrogenation reaction but suffers from the difficulty of tailoring the microstructure and surface properties. Herein, we developed a MOF-derived Cu/SiO2 catalyst (Cu/SiO2-MOF) for FF hydrogenation to 2-methyl furan (2-MF). In comparison with Cu/SiO2 catalysts prepared from ammonia evaporation (Cu/SiO2-AE) and traditional impregnation (Cu/SiO2-TI), the copper species in Cu/SiO2-MOF could not only be anchored on the silica surface via forming Cu-O-Si bonds but also exposed many more active sites. In this way, a higher ratio of Cu+/(Cu+ + Cu0) and richer oxygen defects were constructed via strong metal-support interactions, which were responsible for the superior catalytic performance. In addition, it was found that the solvent effect on product distribution played an important role in adjusting the selectivity to 2-MF and cyclopentanone (CPO). The present work not only provides a deep insight into the catalytic mechanism of Cu/SiO2-MOF for the FF hydrogenation reaction but also sheds light on the design and synthesis of highly efficient catalysts for other heterogeneous catalysis fields.

Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle.

The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10-7 and p < 1.89 × 10-7, respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens.

Siliceous Origin of the Cambrian Qiongzhusi Formation Shale in the Middle Part of the Upper Yangtze Platform: Significance of Organic Matter Enrichment.

The early Cambrian Qiongzhusi Formation shale is rich in organic matter and is a high-quality marine Source rock. However, the origin of Qiongzhusi Formation siliceous rocks is unknown, and the role of siliceous rocks in the process of organic matter enrichment or preservation is also lacking. This study combines thin section, scanning electron microscopy, SEM/EDS, major and trace element analysis, and N2 adsorption experiments to analyze and evaluate the shale of the Qiongzhusi Formation in the central region of the Sichuan Basin. The quartz types in the shale of the Qiongzhusi Formation are divided into four types, namely, bioclastic siliceous rocks, terrestrial detrital quartz, siliceous microcrystalline quartz particles, and microcrystalline quartz aggregates; at the same time, according to petrographic and geochemical parameters, the content of authigenic quartz in Qiongzhusi Formation shale decreases from top to bottom, and terrigenous detrital quartz tends to increase, and biogenic silicon accounts for the majority of authigenic quartz components; autogenous quartz has a positive impact on the pore structure of shale, providing sufficient pore space for the development of organic pores and protecting the internal pore network by forming intergranular pores as rigid frameworks. At the same time, it plays a crucial role in the enrichment and preservation of organic matter.

Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.

BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.

Surface-sealing encapsulation of phosphotungstic acid in microporous UiO-66 as a bifunctional catalyst for transfer hydrogenation of levulinic acid to γ-valerolactone.

The efficient production of γ-valerolactone (GVL) from renewable lignocellulose that is synthesized in plants by photosynthesis to replace the declining fossil resources conforms to the principles of circular economy. Compared to direct hydrogenation by H2 molecules, catalytic transfer hydrogenation (CTH) of levulinic acid (LA) and/or its esters to GVL with organic alcohols as a hydrogen source is a much milder route. The synergistic catalysis between Lewis and Brønsted acids is indispensable in the CTH process. Considering that unsaturated coordinated Zr species could act as Lewis acid sites and phosphotungstic acid (PTA) could dissociate protons as Brønsted acid sites, UiO-66 (Zr) was thus "acidified" by encapsulating PTA in its channels to tune the ratio of Brønsted to Lewis acid sites as a bifunctional catalyst so as to better understand the catalytic structure-performance relationship in the CTH process. To address the dilemma of encapsulated PTA that is prone to leach, a rapid surface sealing strategy was adopted to establish a polyimide (PI) coating over the surface of UiO-66 introducing a space confinement effect via an anhydride-amine coupling reaction. The as-synthesized PTA/UiO-66@PI catalyst exhibited 100% of LA conversion, a 93.2% of GVL yield and high recyclability for at least five consecutive cycles. Moreover, a reaction pathway followed by esterification, hydrogenation and dealcoholization as well as a catalytic hydrogenation mechanism based on intermolecular hydride ß-H transfer were proposed. Current work not only provides a high-performance and high-stability catalytic system to selectively produce GVL from LA or its esters, but also sheds light on the catalytic mechanism of the CTH process at the molecular level.

SPI1-mediated MIR222HG transcription promotes proneural-to-mesenchymal transition of glioma stem cells and immunosuppressive polarization of macrophages.

Background: Glioma stem cells (GSCs) are a key factor in glioblastoma (GBM) development and treatment resistance. GSCs can be divided into the mesenchymal (MES) and proneural (PN) subtypes, and these two subtypes of GSCs can undergo interconversion under certain conditions. MES GSCs have higher malignancy and radioresistance and are closely associated with an immunosuppressive microenvironment. Long noncoding RNAs (lncRNAs) play a broad role in GBM, while the role of GSCs subtype remains unknown. Methods: We performed RNA sequencing to explore the lncRNA expression profile in MES- and PN-subtype GBM tissues. The biological function of a host gene-MIR222HG-in GBM development was confirmed in vitro and in vivo. Specifically, RNA sequencing, RNA pulldown, mass spectrometry, RIP, ChIP, luciferase reporter assays and Co-IP were performed. Results: MIR222HG, the expression of which can be induced by SPI1, has high levels in MES GBM tissues. Functionally, we demonstrated that MIR222HG promotes the MES transition and radioresistance in GSCs in vivo and in vitro. Mechanistically, MIR222HG can bind to the YWHAE/HDAC5 complex to promote the MES transition of GSCs through H4 deacetylation. Moreover, cotranscribed miR221 and miR222 can be delivered to macrophages via exosomes to target SOCS3, causing immunosuppressive polarization. Finally, PLX-4720 sensitivity is associated with SPI1 expression and acts on MES GSCs to enhance radiosensitivity. Conclusions: This study demonstrates that targeting SPI1 to block transcription of the MIR222HG cluster helps to reduce radioresistance and combat the immunosuppressive microenvironment in GBM. PLX-4720 is a potential GBM drug and radiosensitizer.

Long-term effects of a tailored mindfulness-based program for Chinese intensive care unit nurses: A randomized parallel-group trial.

AIM: This study investigated the direct and long-term improvements that mindfulness-based interventions exert on intensive care unit nurses. We assessed an abbreviated four-week, twice-weekly mindfulness-based intervention program's effect on work-related mental health variables and examined whether the intervention impact was maintained at two- and six-month follow-up assessments. We also examined the training program's effects on work and life. BACKGROUND: Previous research has shown that mindfulness interventions exert positive effects immediately after treatment. However, few studies have examined whether treatment effects are maintained over time or under different circumstances. Moreover, treatment effects among Chinese intensive care unit nurses have rarely been examined. DESIGN: We conducted a randomized, non-blinded, parallel-group trial. METHODS: Participants included 90 intensive care unit nurses, divided into two cohorts, who participated in the program in October 2016 and April 2017. They completed validated measures of mindfulness, burnout syndromes, anxiety and depressive symptoms and well-being at baseline (T1), immediately after intervention (T2), two months after (T3) and six months after (T4) the intervention. RESULTS: We observed a significant group effect (1) immediately post-intervention and two months after intervention for mindfulness; (2) at two months after intervention for anxiety, depression and subjective well-being and (3) at post-intervention, two months after and six months after for emotional exhaustion. CONCLUSIONS: These findings suggest that the tailored four-week mindfulness-based intervention program improved intensive care unit nurses' mental health, although further research is needed to verify its feasibility in a clinical working environment.

Systematic analysis of the aberrances and functional implications of cuproptosis in cancer.

Cuproptosis is a novel form of cell death driven by a copper-dependent proteotoxic stress response whose comprehensive landscape in tumors remains unclear. Here, we comprehensively characterized cuproptosis-related genes (CRGs) across 33 cancers using multi-omic data from The Cancer Genome Atlas (TCGA), showing complicated and diverse results in different cancers. We also explored the relationships between CRGs and cancer metabolic patterns, pathway activity, and tumor microenvironment (TME), suggesting that they played critical roles in tumor progression and TME cell infiltration. We further established the cuproptosis potential index (CPI) to reveal the functional roles of cuproptosis, and characterized multi-omic molecular features associated with cuproptosis. In clinical applications, we performed a combined analysis of the sensitivity of CRGs and CPI to drug response and immunotherapy. This study provides a rich resource for understanding cuproptosis, offering a broad molecular perspective for future functional and therapeutic studies of multiple cancer pathways mediated by cuproptosis.

Glioblastoma upregulates SUMOylation of hnRNP A2/B1 to eliminate the tumor suppressor miR-204-3p, accelerating angiogenesis under hypoxia.

Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.