Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture.

Exposures to complex environmental chemical mixtures during pregnancy reach and target the feto-placental unit. This study investigates the influence of environmental chemical mixtures on placental bioenergetics. Recognizing the essential role of the epidermal growth factor receptor (EGFR) in placental development and its role in stimulating glycolysis and mitochondrial respiration in trophoblast cells, we explored the effects of chemicals known to disrupt EGFR signaling on cellular energy production. Human primary cytotrophoblasts (hCTBs) and a first-trimester extravillous trophoblast cell line (HTR-8/SVneo) were exposed to a mixture of EGFR-interfering chemicals, including atrazine, bisphenol S, niclosamide, PCB-126, PCB-153, and trans-nonachlor. An RNA sequencing approach revealed that the mixture altered the transcriptional signature of genes involved in cellular energetics. Next, the impact of the mixture on cellular bioenergetics was evaluated using a combination of mitochondrial and glycolytic stress tests, ATP production, glucose consumption, lactate synthesis, and super-resolution imaging. The chemical mixture did not alter basal oxygen consumption but diminished the maximum respiratory capacity in a dose-dependent manner, indicating a disruption of mitochondrial function. The respiratory capacity and ATP production were increased by EGF, while the Chem-Mix reduced both EGF- and non-EGF-mediated oxygen consumption rate in hCTBs. A similar pattern was observed in the glycolytic medium acidification, with EGF increasing the acidification, and the Chem-Mix blocking EGF-induced glycolytic acidification. Furthermore, direct stochastic optical reconstruction microscopy (dSTORM) imaging demonstrated that the Chem-Mix led to a reduction of the mitochondrial network architecture, with findings supported by a decrease in the abundance of OPA1, a mitochondrial membrane GTPase involved in mitochondrial fusion. In conclusion, we demonstrated that a mixture of EGFR-disrupting chemicals alters mitochondrial remodeling, resulting in disturbed cellular bioenergetics, reducing the capacity of human cytotrophoblast cells to generate energy. Future studies should investigate the mechanism by which mitochondrial dynamics are disrupted and the pathological significance of these findings.

Lack of Efficacy of Simvastatin Adjunctive Therapy for Patients with Schizophrenia: A Meta-Analysis of Randomized Controlled Trials.

Background: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials. Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics. Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of -0.36 (95% Confidence Interval, CI: -0.82 to 0.11) at 1 month, and -1.80 (95% Confidence Interval, CI: -4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%). Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.

Short-term temperature changes affected the predation ability of Orius similis on Bemisia tabaci nymphs.

Bemisia tabaci (Gennadius), a major pest that can adversely affect economies and agriculture globally, is particularly sensitive to climate change-induced temperature fluctuations, which can intensify its outbreaks. Orius similis Zheng, a primary natural predator of B. tabaci, also experiences temperature-related effects that influence its biocontrol efficacy. Thus, understanding the response of O. similis to temperature changes is pivotal for optimizing its biocontrol potential. Herein, our investigations showed that the functional response of O. similis to both high- and low-instar nymphs of B. tabaci adheres to the type II model at temperatures of 19, 22, 25, 28, and 31 °C. At 28 °C, O. similis exhibits the highest instantaneous attack rate (high-instar: 1.1580, low-instar: 1.2112), and the shortest handling time per prey (high-instar: 0.0218, low-instar: 0.0191). The efficacy of O. similis in controlling B. tabaci nymphs follows the sequence: 28 °C > 25 °C > 31 °C > 22 °C > 19 °C. Additionally, search efficiency inversely correlates with prey density. Simulations using the Hessell-Varley interference model indicate that increased density of O. similis under any temperature condition leads to reduced predation rates. Moreover, O. similis shows a predation preference for low-instar nymphs of B. tabaci, with higher predation level observed at the same temperature. In conclusion, for effective control of B. tabaci in field releases, O. similis should be optimally released at temperatures between 25 and 28 °C to preferably target the egg or early nymph stages of B. tabaci and determining the appropriate number of O. similis is important to minimize interference among individuals and enhance biocontrol efficacy.

ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.

Proteostasis and genomic integrity are respectively regulated by the endoplasmic reticulum-associated protein degradation (ERAD) and DNA damage repair signaling pathways, with both pathways essential for carcinogenesis and drug resistance. How these signaling pathways coordinate with each other remains unexplored. We found that ER stress specifically induces the DNA-PKcs-regulated nonhomologous end joining (NHEJ) pathway to amend DNA damage and impede cell death. Intriguingly, sustained ER stress rapidly decreased the activity of DNA-PKcs and DNA damage accumulated, facilitating a switch from adaptation to cell death. This DNA-PKcs inactivation was caused by increased KU70/KU80 protein degradation. Unexpectedly, the ERAD ligase HRD1 was found to efficiently destabilize the classic nuclear protein HDAC1 in the cytoplasm, by catalyzing HDAC1's polyubiquitination at lysine 74, at a late stage of ER stress. By abolishing HDAC1-mediated KU70/KU80 deacetylation, HRD1 transmits ER signals to the nucleus. The resulting enhanced KU70/KU80 acetylation provides binding sites for the nuclear E3 ligase TRIM25, resulting in the promotion of polyubiquitination and the degradation of KU70/KU80 proteins. Both in vitro and in vivo cancer models showed that genetic or pharmacological inhibition of HADC1 or DNA-PKcs sensitizes colon cancer cells to ER stress inducers, including the Food and Drug Administration-approved drug celecoxib. The antitumor effects of the combined approach were also observed in patient-derived xenograft models. These findings identify a mechanistic link between ER stress (ERAD) in the cytoplasm and DNA damage (NHEJ) pathways in the nucleus, indicating that combined anticancer strategies may be developed that induce severe ER stress while simultaneously inhibiting KU70/KU80/DNA-PKcs-mediated NHEJ signaling.

Meta-analysis and systematic review of the diagnostic value of contrast-enhanced spectral mammography for the detection of breast cancer.

OBJECTIVE: The objective is to evaluate the diagnostic effectiveness of contrast-enhanced spectral mammography (CESM) in the diagnosis of breast cancer. DESIGN: DATA SOURCES: PubMed, Embase and Cochrane libraries up to 18 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included trials studies, compared the results of different researchers on CESM in the diagnosis of breast cancer, and calculated the diagnostic value of CESM for breast cancer. DATA EXTRACTION AND SYNTHESIS: Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) evaluated the methodological quality of all the included studies. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses specification. In addition to sensitivity and specificity, other important parameters were explored in an analysis of CESM accuracy for breast cancer diagnosis. For overall accuracy estimation, summary receiver operating characteristic curves were calculated. STATA V.14.0 was used for all analyses. RESULTS: This meta-analysis included a total of 12 studies. According to the summary estimates for CESM in the diagnosis of breast cancer, the pooled sensitivity and specificity were 0.97 (95% CI 0.92 to 0.98) and 0.76 (95% CI 0.64 to 0.85), respectively. Positive likelihood ratio was 4.03 (95% CI 2.65 to 6.11), negative likelihood ratio was 0.05 (95% CI 0.02 to 0.09) and the diagnostic odds ratio was 89.49 (95% CI 45.78 to 174.92). Moreover, there was a 0.95 area under the curve. CONCLUSIONS: The CESM has high sensitivity and good specificity when it comes to evaluating breast cancer, particularly in women with dense breasts. Thus, provide more information for clinical diagnosis and treatment.

Mechanism of fatty acid transposase (CD36) promoting fat accumulation in mule ducks.

Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression. This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.

A GDSL motif-containing lipase modulates Sclerotinia sclerotiorum resistance in Brassica napus.

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum (Lib.) De Bary is a devastating disease infecting hundreds of plant species. It also restricts the yield, quality, and safe production of rapeseed (Brassica napus) worldwide. However, the lack of resistance sources and genes to S. sclerotiorum has greatly restricted rapeseed SSR-resistance breeding. In this study, a previously identified GDSL motif-containing lipase gene, Brassica napus GDSL LIPASE-LIKE 1 (BnaC07.GLIP1), encoding a protein localized to the intercellular space, was characterized as functioning in plant immunity to S. sclerotiorum. The BnaC07.GLIP1 promoter is S. sclerotiorum-inducible and the expression of BnaC07.GLIP1 is substantially enhanced after S. sclerotiorum infection. Arabidopsis (Arabidopsis thaliana) heterologously expressing and rapeseed lines overexpressing BnaC07.GLIP1 showed enhanced resistance to S. sclerotiorum, whereas RNAi suppression and CRISPR/Cas9 knockout B. napus lines were hyper-susceptible to S. sclerotiorum. Moreover, BnaC07.GLIP1 affected the lipid composition and induced the production of phospholipid molecules, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidic acid, which were correlated with decreased levels of reactive oxygen species (ROS) and enhanced expression of defense-related genes. A B. napus bZIP44 transcription factor specifically binds the CGTCA motif of the BnaC07.GLIP1 promoter to positively regulate its expression. BnbZIP44 responded to S. sclerotiorum infection, and its heterologous expression inhibited ROS accumulation, thereby enhancing S. sclerotiorum resistance in Arabidopsis. Thus, BnaC07.GLIP1 functions downstream of BnbZIP44 and is involved in S. sclerotiorum resistance by modulating the production of phospholipid molecules and ROS homeostasis in B. napus, providing insights into the potential roles and functional mechanisms of BnaC07.GLIP1 in plant immunity and for improving rapeseed SSR disease-resistance breeding.

Effects of a Remote Multimodal Psychoeducational Intervention Nursing Program on Mental Health and Quality of Life of Renal Cell Carcinoma Survivors: A Retrospective Study.

BACKGROUND: Undergoing surgery for renal cell carcinoma can potentially compromise the mental well-being and overall quality of life of survivors. Long-term psychological education interventions that are delivered remotely through various modalities have shown promise in enhancing the psychological well-being and quality of life of cancer patients. This study investigates the effect of remote multimodal psychoeducational interventions on mental well-being and quality of life of renal cell carcinoma survivors. METHODS: A retrospective study was conducted to compare patients receiving remote psychological interventions (exposure group) with those receiving standard care (control group). Following the interventions, various data sets including general demographic information, and assessments from the Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), the Brief Fatigue Inventory-Chinese version (BFI-C), the Distress Thermometer (DT), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) were gathered and analysed for comparison. RESULTS: This study included 116 renal cell carcinoma survivors, with 52 in the exposure group and 64 in the control group. Baseline characteristics were not significantly different between the two groups (p > 0.05). After the intervention, the exposure group had significantly lower scores than the control group on HAMA (14.63 vs. 16.66, p < 0.001), HAMD (13.63 vs. 16.36, p < 0.001), BFI-C (52.31 vs. 57.65, p < 0.001), and DT (3.94 vs. 4.98, p < 0.001). Additionally, the exposure group had significantly higher total score of EORTC QLQ-C30 (69.22 vs. 65.59, p < 0.001) than the control group. CONCLUSIONS: Remote multimodal psychoeducational interventions demonstrate a notable impact in mitigating adverse emotions, exhaustion, and discomfort experienced by survivors of renal cell carcinoma. Such interventions should be actively promoted in clinical practice.

Electrical-Modulated Flexible Acoustic Metamaterial: Enhancing Low-Frequency Absorption via an Ionic Electroactive Polymer.

The growing concern over low-frequency noise pollution resulting from global industrialization has posed substantial challenges in noise attenuation. However, conventional acoustic metamaterials, with fixed geometries, offer limited flexibility in the frequency range adjustment once constructed. This research unveiled the promising potential of ionic electroactive polymers, particularly ionic polymer-metal composites (IPMCs), as a superior candidate to design tunable acoustic metamaterial due to its bidirectional energy conversion capabilities. The previously perceived limitations of the IPMC, including slow reaction and high energy expenditure, owning to its inherent sluggish intermediary ionic mass transport process, were astutely leveraged to expedite the attenuation of low-frequency sound energy. Both our experimental and simulation results elucidated that the IPMC can generate voltage potentials in response to acoustic pressure at frequencies significantly higher than those previously established. In addition, the peak absorption frequency can be effectively shifted by up to 45.7% with the application of a 4 V voltage. By further integration with a microperforated panel (MPP) structure, the developed metamaterial absorbers can achieve complete sound absorption, which was continuously tunable under minimal voltage stimulation across a wide frequency spectrum. In addition, a microslit structure IPMC metamaterial absorber was designed to realize modulation of the perforation rate, and the absorption peak can be shifted by up to 79.2%. These findings signify a pioneering application of ionic intelligent materials and may pave the way for further innovations of tunable low-frequency acoustic structures, ultimately advancing the pragmatic deployment of both soft intelligent materials and acoustic metamaterials.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China.

Objective: To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (EGFR) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety. Methods: A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with vs. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg vs. 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the EGFR 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% vs. 7.5%, P=0.042). Conclusions: First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Construction of polypyrrole nanoparticles with a rough surface for enhanced chemo-photothermal therapy against triple negative breast cancer.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.

Development of Extubation Success Prediction Model for Mechanically Ventilated Patients with Spontaneous Cerebellar Hemorrhage.

Spontaneous cerebellar hemorrhage (SCH) patients have a low success rate in extubation, but there are currently no guidelines establishing specifically for SCH patients extubation. The study included 68 SCH patients who received mechanical ventilation for more than 24 h, with 39 cases (57.3%) resulting in successful extubation. The multivariate analysis identified four factors significantly associated with extubation success: patient age under 66 years, an Intracerebral Hemorrhage (ICH) score less than 4 points, the presence of tissue shift, and a Glasgow Coma Scale (GCS) score (excluding language) above 6 points at extubation. By simplifying the prediction model, we obtained the Spontaneous Cerebellar Hemorrhage Extubation Success scoring system (SCHES-SCORE). Within the scoring system, 2 points were allocated for a GCS score (excluding language) above 6 at extubation, 1 point each for age under 66 years and an ICH score below 4, while tissue shift was assigned a negative point. A score of Grade A (SCHES-SCORE = 3-4) was found to correlate with a 92.9% success rate for extubation. The area under the receiver operating characteristic curve was 0.923 (95% CI, 0.863 to 0.983). Notably, successful extubation was significantly linked to reduced durations of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. In conclusion, the scoring system developed for assessing extubation outcomes in SCH patients has the potential to enhance the rate of successful extubation and overall patient outcomes.

Exploring cognitive related microstructural alterations in normal appearing white matter and deep grey matter for small vessel disease: A quantitative susceptibility mapping study.

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to alleviate ulcerative colitis.

Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.

Scale-Up, Continuous and Low-Temperature Production of Multimetal Based Electrocatalysts toward Water Electrolysis.

Electrocatalytic water splitting is a crucial strategy for advancing hydrogen energy and addressing the global energy crisis. Despite its significance, the need for a straightforward and swift method to synthesize electrocatalysts with exceptional performance remains pressing. In this study, we demonstrate a novel approach for the preparation of multimetal-based electrocatalysts in a continuous flow reactor, enabling the quick synthesis of a large number of products through a streamlined process. The resultant NiFe-LDH comprises nanoflakes with a high specific surface area and requires only 255.4 mV overpotential to achieve a current density of 10 mA·cm-2 in 1 M KOH, surpassing samples fabricated by conventional hydrothermal methods. Our method can also be applied to craft a spectrum of other multimetal-based electrocatalysts, including CoFe-LDH, CoAl-LDH, NiMn-LDH, and NiCoFe-LDH. Additionally, the NiFe-LDH electrocatalyst is further applied to anodic methanol electrooxidation coupled with cathodic hydrogen evolution. Moreover, the simplicity and generality of our fabrication method render it applicable for the facile preparation of various multimetal-based electrocatalysts, offering a scalable solution to the quest for high-performance catalysts in advancing sustainable energy technologies.

Prevalence and risk factors of sleep disturbances among patients with lung cancer: systematic review and meta-analysis.

PURPOSE: Patients with lung cancer endure the most sleep problems. Understanding the prevalence and risk factors of sleep disturbances in lung cancer populations is critical in reducing symptom burden and improving their quality of life. This systematic review aimed to determine the prevalence and risk factors of sleep disturbances in patients with lung cancer. METHODS: Seven electronic databases were systematically screened for studies on the prevalence or risk factors of sleep disturbances in patients with lung cancer. Subgroup analyses were conducted to investigate significant heterogeneity (I2 > 50%) across studies. RESULTS: Thirty-seven studies were found eligible. The pooled prevalence was 0.61 (95% CI = [0.54-0.67], I2 = 96%, p < 0.00001). Seven risk factors were subject to meta-analyses. Significant differences were found for old age (OR = 1.23; 95% CI = [1.09-1.39], p = 0.0006,I2 = 39%), a low education level (OR = 1.17; 95%CI = [1.20-2.66], p = 0.004, I 2 = 42%), fatigue (OR = 1.98; 95%CI = [1.23-3.18], p = 0.005, I 2 = 31%), pain (OR = 2.63; 95% CI = [1.35-5.14], p = 0.005, I 2 = 91%), tumor stage of III or IV (OR = 2.05; 95%CI = [1.54-2.72], p < 0.00001, I 2 = 42%), anxiety (OR = 1.62; 95%CI = [1.22-2.14], p = 0.0008, I2 = 78%), and depression (OR = 4.02; 95% CI = [1.39-11.61], p = 0.01, I2 = 87%). After the included studies were withdrawn one after the other, pain (OR = 3.13; 95% CI = [2.06-4.75], p < 0.00001, I 2 = 34%) and depression (OR = 5.47; 95% CI = [2.65-11.30], p < 0.00001) showed a substantial decrease of heterogeneity. Meanwhile, the heterogeneity of anxiety symptoms remained unchanged. CONCLUSION: Results showed that sleep disturbances were experienced in more than 60% of patients with lung cancer. The comparatively high prevalence of sleep disturbances in this population emphasizes the need to adopt measures to reduce them. Significant associations were found between sleep disturbances and various factors, including age, education level, fatigue, pain, cancer stage, anxiety, and depression. Among these factors, depression emerged as the most significant. Future research should concentrate on identifying high-risk individuals and tailored interdisciplinary interventions based on these risk factors.

GABPA-Mediated Expression of HPN-AS1 Facilitates Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma by Promoting eIF4A3 Degradation.

Hepatocellular carcinoma (HCC) represents a common neoplasm that presents a substantial worldwide health challenge. Nevertheless, the involvement of HPN-AS1 in HCC remains unknown. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was utilized to measure HPN-AS1 expression in HCC. The GABPA effects on the HPN-AS1 promoter were analyzed through chromatin immunoprecipitation and luciferase reporter assays. Cell proliferation potential was determined by deploying CCK-8 assay, Ki-67 immunofluorescence staining, and colony formation assay. Cell apoptosis was detected using acridine orange/ethidium bromide staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Western blotting was utilized to measure the protein levels of proliferation factors and apoptosis regulators. HPN-AS1 binding to eIF4A3 was accessed by RNA-binding protein immunoprecipitation assay. HPN-AS1 was significantly downregulated in both HCC cells and tissues. Lower HPN-AS1 levels indicate a poorer HCC prognosis. Moreover, we found that GABPA functions as a transcription factor for HPN-AS1. Functional studies revealed that HPN-AS1 displayed inhibitory effects on HCC cell proliferation and promoted apoptosis. Mechanically, HPN-AS1 bound to and facilitated translation initiation factor eIF4A3 degradation. Loss of HPN-AS1 augmented eIF4A3 protein levels rather than eIF4A3 mRNA levels. Exogenous expression of eIF4A3 could restore eIF4A3 protein levels and reverse HPN-AS1 overexpression-induced cell proliferation inhibition and cell apoptosis. Our study elucidated that HPN-AS1 downregulation was mediated by GABPA. HPN-AS acted as a tumor suppressor within HCC through binding and facilitating eIF4A3 degradation. The study provides a novel insight into the biological function of HPN-AS1 in HCC, suggesting that HPN-AS1 could be a promising biomarker and a potential target for HCC diagnosis and treatment.

Light People: Prof. Donal D C Bradley (FRS).

EDITORIAL: The invention of organic light emitting diodes (LEDs) led to enormous excitement in both academe and industry in the late 1980's. Flexibility, large area solution processability, roll-to-roll printing, low cost, and environmentally friendly are some of the advantages of organic semiconductor materials, which brought a new horizon for optoelectronics. Together with the achievement of organic solar cells, transistors, lasers, and amplifiers, this has demonstrated potential applications of organic semiconductors in displays, lighting, solar energy generation, electronics, sensing and imaging, and many aspects of photonics. In an enlightened conversation with Light: Science & Applications, Prof. Donal Bradley (FRS), a pioneer in the field, shared his deep insights on past, current, and future exciting developments of organic optoelectronic materials and devices. In particular, he expressed his opinion on the hot topics related to organic optoelectronics research and application, such as the relationship between organic and inorganic semiconductors and the challenge of electrically pumped organic lasers. As a successful scientist, Donal has also been co-founder of several organic optoelectronics innovation companies and research centers and a long-term academic administrator serving as a Head of Department, Centre Director, and Vice-Rector for Research at Imperial College, Head of the Mathematical, Physical, and Life Sciences Division at the University of Oxford, Vice-President for Research at King Abdullah University of Science and Technology and now Vice-President for Research and Innovation at NEOM U and Executive Director of the NEOM Education, Research and Innovation Foundation. Through this interview, we also explore the major roles and events in Donal's career experience from the invention of the first conjugated polymer LED in the world to the set-up of entrepreneurial companies, from Cambridge to Sheffield, Imperial College, and Oxford, from the UK to overseas, and from the establishment of the Centre for Plastic Electronics in Imperial College to the set-up of the Oxford Suzhou Centre for Advanced Research (OSCAR). Before the end of the conversation, he also shares his interesting story of identifying a new species of Sea Bream, Acanthopagrus oconnorae (Bev Bradley's Bream), named after his mother and wife, while fishing in the Red Sea.

Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors.

Lung cancer is the top cause of cancer deaths globally. Advances in immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but their use in lung cancer has led to more side effects. This study examined if past pulmonary tuberculosis (TB) affects ICIs' effectiveness and safety in lung cancer treatment. We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022. We compared outcomes and side effects between patients with and without prior TB. Of 116 patients (40 with TB history, 76 without), prior TB didn't reduce treatment effectiveness but did increase severe side effects. Notably, older patients (≥ 65 years) faced a higher risk of severe side effects. Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs, stressing the need for careful monitoring and personalized care.