Effects of repetitive transcranial magnetic stimulation on fear of cancer recurrence and its underlying neuromechanism.

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment. Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated. Ethics and dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. Trial registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.

A Novel Near-Infrared Fluorescent Probe for the Detection of Endogenous Peroxynitrite (ONOO-) in Living Cells.

In this study, we present a novel near-infrared (NIR) fluorescent probe Nile-ONO designed for the selective and sensitive detection of ONOO-. The probe Nile-ONO employed Nile red as the fluorophore, with diphenylphosphinate serving as the reaction site. In the presence of ONOO-, the probe Nile-ONO exhibits remarkable fluorescence enhancement at 659 nm, with a response time of less than 20 min and a low detection limit of 0.32 µM. Importantly, MTT assays demonstrate low cytotoxicity in living cells. Furthermore, Nile-ONO has excellent imaging capabilities for endogenous ONOO-. Overall, this work introduces a valuable new method for the rapid detection of ONOO- in biological systems.

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC.

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.

Mindfulness-based intervention for hypertension patients with depression and/or anxiety in the community: a randomized controlled trial.

OBJECTIVE: To evaluate mindfulness-based intervention for hypertension with depression and/or anxiety. METHODS: 10-week mindfulness-based intervention, including health education for hypertension, exclusively for the control group, was administered to the intervention group to assist sixty hypertension patients with depression/anxiety. Among them, the intervention group comprised 8 men and 22 women, with a mean age of 60.02 years and a mean duration of hypertension of 6.29 years. The control group consisted of 14 men and 16 women with a mean age of 57.68 years and a mean duration of hypertension of 6.32 years. The severity of depressive and/or anxiety symptoms was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7), along with blood pressure (BP) measurements taken twice daily. The study utilized a self-made self-efficacy scale and awareness of physical and mental health to evaluate mental health and state. RESULTS: The depression PHQ-9 or GAD-7 scores reduced by 21.1% or 17.8% in the mindfulness-based intervention group, compared to the control (Z = -2.040, P = 0.041) post 10-week period, suggesting significant reduction in anxiety/stress. These results were consistent with a reduction in systolic BP of 12.24 mm Hg (t = 6.041, P = 0.000). The self-efficacy score of the mindfulness intervention group significantly improved compared to the control (t = 7.818, P < 0.001), while the awareness of physical and mental health in the mindfulness intervention group significantly improved compared to the control (χ2 = 5.781, P = 0.016). CONCLUSION: Mindfulness-based, short-term focused interventions provide modest relief for depression and/or anxiety and are effective in lowering blood pressure and improving self-efficacy scores. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900028258. Registered 16 December 2019, https://www.chictr.org.cn/showproj.html?proj=43627 .

The relative contribution of PM2.5 components to the obstructive ventilatory dysfunction-insights from a large ventilatory function examination of 305,022 workers in southern China.

BACKGROUND: The new round of WHO/ILO Joint Estimates of the Work-related Burden of Disease assessment requires futher research to provide more evidence, especially on the health impact of ambient air pollution around the workplace. However, the evidence linking obstructive ventilatory dysfunction (OVD) to fine particulate matter (PM2.5) and its chemical components in workers is very limited. Evidence is even more scarce on the interactive effects between occupational factors and particle exposures. We aimed to fill these gaps based on a large ventilatory function examination of workers in southern China. METHODS: We conducted a cross-sectional study among 363,788 workers in southern China in 2020. The annual average concentration of PM2.5 and its components were evaluated around the workplace through validated spatiotemporal models. We used mixed-effect models to evaluate the risk of OVD related to PM2.5 and its components. Results were further stratified by basic characteristics and occupational factors. FINDINGS: Among the 305,022 workers, 119,936 were observed with OVD. We found for each interquartile range (IQR) increase in PM2.5 concentration, the risk of OVD increased by 27.8 (95 % confidence interval (CI): 26.5-29.2 %). The estimates were 10.9 % (95 %CI: 9.7-12.1 %), 15.8 % (95 %CI: 14.5-17.2 %), 2.6 % (95 %CI: 1.4-3.8 %), 17.1 % (95 %CI: 15.9-18.4 %), and 11 % (95 %CI: 9.9-12.2 %), respectively, for each IQR increment in sulfate, nitrate, ammonium salt, organic matter and black carbon. We observed greater effect estimates among females, younger workers, workers with a length of service of 24-45 months, and professional skill workers. Furthermore, it is particularly noteworthy that the noise-exposed workers, high-temperature-exposed workers, and less-dust-exposed workers were at a 5.7-68.2 % greater risk than others. INTERPRETATION: PM2.5 and its components were significantly associated with an increased risk of OVD, with stronger links among certain vulnerable subgroups.

Multi-omics reveal the gut microbiota-mediated severe foraging environment adaption of small wild ruminants in the Three-River-Source National Park, China.

The Tibetan antelope (Pantholops hodgsonii), blue sheep (Pseudois nayaur), and Tibetan sheep (Ovis aries) are the dominant small ruminants in the Three-River-Source National Park (TRSNP). However, knowledge about the association between gut microbiota and host adaptability remains poorly understood. Herein, multi-omics sequencing approaches were employed to investigate the gut microbiota-mediated forage adaption in these ruminants. The results revealed that although wild ruminants (WR) of P. hodgsoni and P. nayaur were faced with severe foraging environments with significantly low vegetation coverage and nutrition, the apparent forage digestibility of dry matter, crude protein, and acid detergent fiber was significantly higher than that of O. aries. The 16s rRNA sequencing showed that the gut microbiota in WR underwent convergent evolution, and alpha diversity in these two groups was significantly higher than that in O. aries. Moreover, indicator species, including Bacteroidetes and Firmicutes, exhibited positive relationships with apparent forage digestibility, and their relative abundances were enriched in the gut of WR. Enterotype analysis further revealed that enterotype 1 belonged to WR, and the abundance of fatty acid synthesis metabolic pathway-related enzyme genes was significantly higher than enterotype 2, represented by O. aries. Besides, the metagenomic analysis identified 14 pathogenic bacterial species, among which 10 potentially pathogenic bacteria were significantly enriched in the gut microbiota of O. aries. Furthermore, the cellulolytic strains and genes encoding cellulase and hemicellulase were significantly enriched in WR. In conclusion, our results provide new evidence of gut microbiota to facilitate wildlife adaption in severe foraging environments of the TRSNP, China.

Epidemiological Features of Hepatitis C in China From 2015 to 2021: Insights From National Surveillance Data.

The COVID-19 pandemic overwhelmed national health care systems, not least in the context of hepatitis elimination. This study investigates the effects of the pandemic response on the incidence rate, mortality rate, and case fatality rate (CFR) for hepatitis C virus (HCV) cases in China. We extracted the number of hepatitis C cases and HCV-related deaths by month and year for 2015 to 2021 in China and applied two proportional tests to analyze changes in the average yearly incidence rates, mortality rates, and CFRs for 2015 to 2020. We used the autoregressive integrated moving average model to predict these three rates for 2020 based on 2015 to 2019 HCV data. The incidence of hepatitis C decreased by 7.11% and 1.42% (P < .001) in 2020 and 2021, respectively, compared with 2015 to 2019, while it increased by 6.13% (P < .001) in 2021 relative to 2020. The monthly observed incidence in 2020 was significantly lower (-26.07%) than predicted. Meanwhile, no differences in mortality rate or CFR were observed between 2021, 2020, and 2015 to 2019. Our findings suggest that nonpharmaceutical interventions and behavioral changes to mitigate COVID-19 could have reduced hepatitis C incidence and accelerated China's implementation of a plan to eliminate HCV infection.

A study of macroinvertebrate community structure and diversity in response to land use type in the Yiluo River Basin.

The Yiluo River is the largest tributary below Xiaolangdi Reservoir in the middle reaches of the Yellow River, and is one of the important water conservation areas in the Yellow River Basin. Studying the ecological status of the Yiluo River under varied land use types in this basin is crucial for both ecological protection and the high-quality development of the Yellow River Basin. This study investigated the impacts of land use types on the macroinvertebrate community and functional structure in the Yiluo River Basin and introduced the concept of the land use health index (LUI). During the survey period, a total of 11,894 macroinvertebrates were collected, and 143 species were identified, belonging to 4 phyla, 7 orders, 22 families, and 75 families. The results showed that LUI had the most significant impact on macroinvertebrate community structure, with substrate type, dry plant weight, total phosphorus, turbidity, and attached algae biomass also playing significant roles in affecting macroinvertebrate communities. The species richness, the Shannon-Wiener index, and the Margalef richness index exhibited a nonlinear positive correlation with LUI of the sampling site, increasing as LUI enhancing and eventually reaching a plateau. Functional richness showed a linear and positive correlation with LUI, increasing with its enhancement, while functional evenness and functional divergence exhibited a nonlinear correlation with LUI. Functional evenness initially increased and then decreased with the enhancement of LUI, while functional divergence decreased with LUI enhancement. This study can provide a scientific reference for river ecological management under various land use scenarios.

Enhancing proton transport in polyvinylidenedifluoride membranes and reducing biofouling for improved hydrogen production in microbial electrolysis cells.

Hydrophilic porous membranes, exemplified by polyvinylidene fluoride (PVDF) membranes, have demonstrated significant potential for replacing ion exchange membranes in microbial electrolysis cells (MECs). Membrane fouling remains a major challenge in MECs, impeding proton transport and consequently limiting hydrogen production. This study aims to investigate a synergistic antifouling strategy for PVDF membrane through the incorporation of a coating composed of polydopamine (PDA), polyethyleneimine (PEI), and silver nanoparticles (AgNPs). The PDA-PEI-Ag@PVDF membrane not only effectively mitigates fouling through steric and electrostatic repulsion forces, but also amplifies ion transport by facilitating water diffusion and electromigration. The PDA-PEI-Ag@PVDF membrane exhibited a reduced membrane resistance of 1.01 mΩ m2 and PDA-PEI-Ag modifying PVDF membrane was found to be effective in enhancing the proton transportation of PVDF membrane. Therefore, the enhanced hydrogen production rate of 2.65 ± 0.02 m3/m3/d was achieved in PDA-PEI-Ag@PVDF-MECs.

Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis.

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.

Dietary honokiol supplementation improves antioxidant capacity, enhances intestinal health, and modulates cecal microbial composition and function of broiler chickens.

Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms. In total, 240 one-day-old broilers were randomly allocated to 5 dietary treatments, with 6 replicate pens and 8 birds per pen. Birds were fed a basal diet supplemented with 0 (blank control, BC), 100, 200, or 400 mg/kg honokiol (H100, H200, and H400), or 200 mg/kg bacitracin zinc (PC) for 42 d. The results showed that H200 and H400 increased body weight gain (BWG) and decreased feed conversion ratio (FCR) during the starter period (P < 0.05). H100 and H200 increased total superoxide dismutase (T-SOD) activity in the serum and decreased malondialdehyde (MDA) amount in the jejunum on d 42 (P < 0.05). Moreover, H100 increased villus height-to-crypt depth ratio in both the jejunum and ileum on d 21 (P < 0.05). PCR analysis showed that honokiol upregulated intestinal expression of glutathione peroxidase (GSH-Px) and downregulated intestinal expression of inducible nitric oxide synthase (iNOS) on d 42 (P < 0.05). The Shannon index, which represents the microbial alpha diversity, was reduced for the PC, H200, and H400 groups. Notably, honokiol treatment altered the cecal microbial community structure and promoted the enrichment of several bacteria, including Firmicutes and Lactobacillus. Higher production of short-chain fatty acids was observed in the cecal digesta of H100 birds, accompanied by an enriched glycolysis/gluconeogenesis pathway, according to the functional prediction of the cecal microbiota. This study provides evidence that honokiol improves growth performance, antioxidant capacity, and intestinal health of broiler chickens, possibly by manipulating the composition and function of the microbial community.

Association between ACE1 and missed abortion: ACE1 promotes H2O2-induced trophoblast cell injury in vitro†.

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

Benzothiazolium-based NIR AIE photosensitizers with type I and II ROS generation for efficient mitochondria-targeted photodynamic therapy.

In this work, a near-infrared emissive photosensitizer of 3,3-dimethyl-N,N-diphenyl-2-(thiophen-2-yl)-3H-indol-6-amine functionlized benzothiazolium (DPITT) was developed. DPITT exhibited aggregation-induced emission effect and potent type I and II reactive oxygen species generation capacities after white light irradiation. Taking advantage of the cationic feature, DPITT penetrated the cell membrane and selectively accumulated in the mitochondria in living cells. Upon white light irradiation, the photosensitized DPITT was able to induce mitochondrial dysfunction, leading to cell death. Photosensitized DPITT was further applied to disrupt the multicellular tumour spheroids, demonstrating its potential application in inhibiting hypoxic solid tumours.

The characteristics of arterial risk factors and ankle-brachial index in patients with lower extremity chronic venous diseases: results from the BEST study.

BACKGROUND: The aim of our study was to explore the characteristics of the arterial risk factors and ankle-brachial index (ABI) in patients with lower extremity chronic venous disease (LECVD). METHODS: A total of 2642 subjects were employed in our study. The lifestyle and clinical data were collected. The history of vascular diseases contained coronary artery disease, stroke, hypertension, and diabetes. ABI low than 0.9 was considered as lower extremity artery disease (LEAD). A series of blood indicators were measured. RESULTS: Patients with ABI low than 0.9 belonged to the group of LEAD. Age, smoking, drinking, hypertension, diabetes mellitus, lipid-lowering drug, antidiabetic, total protein, total protein, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin and homocysteine were the common risk factors shared by LEAD and LECVD (P<0.05). The prevalence of LEAD in patients with LECVD was higher than those without LECVD (P<0.05). In Pearson correlation analysis, LECVD was related to LEAD (P<0.05). Before and after adjusted shared factors, as the performance of the logistic regression models, LEAD was an independent risk factor for the prevalence of LECVD (OR=2.937, 95% CI: [1.956, 4.411], P<0.001). CONCLUSIONS: Our study demonstrated that an ABI lower than 0.9 is an independent risk factor for LECVD.

[Retracted] The AMPK­mTOR axis requires increased MALAT1 expression for promoting granulosa cell proliferation in endometriosis.

[This retracts the article DOI: 10.3892/etm.2020.9453.].

High-quality faba bean reference transcripts generated using PacBio and Illumina RNA-seq data.

The genome of faba bean was first published in 2023. To promote future molecular breeding studies, we improved the quality of the faba genome based on high-density genetic maps and the Illumina and Pacbio RNA-seq datasets. Two high-density genetic maps were used to conduct the scaffold ordering and orientation of faba bean, culminating in an increased length (i.e., 14.28 Mbp) of chromosomes and a decrease in the number of scaffolds by 45. In gene model mining and optimisation, the PacBio and Illumina RNA-seq datasets from 37 samples allowed for the identification and correction 121,606 transcripts, and the data facilitated a prediction of 15,640 alternative splicing events, 2,148 lncRNAs, and 1,752 fusion transcripts, thus allowing for a clearer understanding of the gene structures underlying the faba genome. Moreover, a total of 38,850 new genes including 56,188 transcripts were identified compared with the reference genome. Finally, the genetic data of the reference genome was integrated and a comprehensive and complete faba bean transcriptome sequence of 103,267 transcripts derived from 54,753 uni-genes was formed.

The significance of precisely regulating heme oxygenase-1 expression: Another avenue for treating age-related ocular disease?

Aging entails the deterioration of the body's organs, including overall damages at both the genetic and cellular levels. The prevalence of age-related ocular disease such as macular degeneration, dry eye diseases, glaucoma and cataracts is increasing as the world's population ages, imposing a considerable economic burden on individuals and society. The development of age-related ocular disease is predominantly triggered by oxidative stress and chronic inflammatory reaction. Heme oxygenase-1 (HO-1) is a crucial antioxidant that mediates the degradative process of endogenous iron protoporphyrin heme. It catalyzes the rate-limiting step of the heme degradation reaction, and releases the metabolites such as carbon monoxide (CO), ferrous, and biliverdin (BV). The potent scavenging activity of these metabolites can help to defend against peroxides, peroxynitrite, hydroxyl, and superoxide radicals. Other than directly decomposing endogenous oxidizing substances (hemoglobin), HO-1 is also a critical regulator of inflammatory cells and tissue damage, exerting its anti-inflammation activity through regulating complex inflammatory networks. Therefore, promoting HO-1 expression may act as a promising therapeutic strategy for the age-related ocular disease. However, emerging evidences suggest that the overexpression of HO-1 significantly contributes to ferroptosis due to its dual nature. Surplus HO-1 leads to excessive Fe2+ and reactive oxygen species, thereby causing lipid peroxidation and ferroptosis. In this review, we elucidate the role of HO-1 in countering age-related disease, and summarize recent pharmacological trials that targeting HO-1 for disease management. Further refinements of the knowledge would position HO-1 as a novel therapeutic target for age-related ocular disease.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation.

Ricin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstrate this correlation and explore its molecular mechanisms. Results showed that RT triggers mouse alveolar macrophage MH-S cells pyroptosis by activating caspase-3 and cleaving Gasgermin E (GSDME). In contrast, inhibition of caspase-3 with Z-DEVD-FMK (inhibitor of caspase-3) or knockdown of GSDME attenuates this process, suggesting the essential role of caspase-3/GSDME-mediated pyroptosis in contributing to RT-induced inflammation. Collectively, our study enhances our understanding of a novel mechanism of ricin cytotoxicity, which may emerge as a potential target in immunotherapy to control the RT-induced inflammation.