A water quality assessment model involving novel fluorescence technology.

The reasonable utilization of water resources and real-time monitoring of water pollution are the core tasks of current world hydrological and water conservancy work. Novel technologies and methods for monitoring water pollution are important means to ensure water health. However, the absence of intuitive and simple analysis methods for the assessment of regional pollution in large-scale water bodies has prevented scientists from quickly grasping the overall situation of water pollution. In this study, we propose a strategy based on the unique combination of fluorescence technology and simple kriging (SK) interpolation (FL-SK) for the first time. This strategy could present the relative magnitude and distribution of the physicochemical indicators of a whole natural lake intuitively and accurately. The unique FL-SK model firstly offers a simple and effective water quality method that provides the pollution index of different sampling points in lakes. The macroscopic evaluation of large-scale water bodies by the FL-SK model primarily relies on the fluorescence response of the RDM-TPE to the comprehensive indicators of the water body, as experimental results have revealed a good correlation between fluorescent responses and six normalized physicochemical indicators. Multiple linear regression and fluorescence response experiments on RDM-TPE indicate that to some extent, the fluorescence signals of the FL-SK model may originate from a certain type of sulfide in the water body. Pattern discovery could enable the analysis of pollution levels in other ecosystems and promote early pollution assessment in the future.

Cardiac involvement in muscular dystrophies: Role of myocardial perfusion imaging.

Technetium-99m-methoxy isobutyl isonitrile (99mTc-MIBI) myocardial perfusion imaging (MPI) is a functional imaging method with relatively poor specificity but high sensitivity. Wepresent 48-year-old man with cardiac involvement due to muscular dystrophies (MD). Myocardial perfusion imaging rest images revealed regional myocardial perfusion decrease in multiple walls, enlarged heart and decreased left ventricular systolic function. The lesion location of MPI was consistent with that seen on CMR. Our case showed MPI was useful for detection and evaluation of the MD patient with cardiac involvement. In addition, imaging findings in combination with clinical history and other data are important. The case highlight is thevalue of MPI in myocardiopathy.

Exploration and Application of a Muscle Fatigue Assessment Model Based on NMF for Multi-Muscle Synergistic Movements.

Muscle fatigue significantly impacts coordination, stability, and speed in daily activities. Accurate assessment of muscle fatigue is vital for effective exercise programs, injury prevention, and sports performance enhancement. Current methods mostly focus on individual muscles and strength evaluation, overlooking overall fatigue in multi-muscle movements. This study introduces a comprehensive muscle fatigue model using non-negative matrix factorization (NMF) weighting. NMF is employed to analyze the duration multi-muscle weight coefficient matrix (DMWCM) during synergistic movements, and four electromyographic (EMG) signal features in time, frequency, and complexity domains are selected. Particle Swarm Optimization (PSO) optimizes feature weights. The DMWCM and weighted features combine to calculate the Comprehensive Muscle Fatigue Index (CMFI) for multi-muscle synergistic movements. Experimental results show that CMFI correlates with perceived exertion (RPE) and Speed Dynamic Score (SDS), confirming its accuracy and real-time tracking in assessing multi-muscle synergistic movements. This model offers a more comprehensive approach to muscle fatigue assessment, with potential benefits for exercise training, injury prevention, and sports medicine.

Selective microRNA expression of exosomes from retinal pigment epithelial cells by oxidative stress.

The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1ß, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future.

Sleep duration time and human papillomavirus infection risk: The U-shaped relationship revealed by NHANES data.

PURPOSE: This study aims to investigate the relationship between sleep factors (sleep duration time [SDT] and obstructive sleep apnea [OSA]) and human papillomavirus (HPV)/high-risk HPV(HR-HPV) infection, utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We conducted a cross-sectional analysis using NHANES data, focusing on SDT and OSA's association with HPV/HR-HPV infection. The primary statistical methods included weighted multivariate linear regression and logistic regression to assess the association between SDT, OSA, and HPV/HR-HPV infection. The study employed restricted cubic splines (RCS) for evaluating potential non-linear relationships between SDT and HPV/HR-HPV infection. Subgroup analyses were conducted. Interaction terms were used to examine the heterogeneity in associations across different subgroups. RESULTS: The study identified a U-shaped relationship between SDT and HPV infection. Specifically, 7 hours of sleep was associated with the lowest risk of HPV infection. In comparison, SDT less than 7 hours resulted in a 26.3% higher risk of HPV infection (Odds Ratio [OR] = 1.26, 95% Confidence Interval [CI]: 1.029, 1.549), and more than 9 hours of sleep showed a 57.4% increased risk (OR = 1.574, 95% CI: 1.116, 2.220). The relationship between SDT and HR-HPV infection was significant in the first two models, but not in the fully adjusted model. No significant interaction was found between sleep duration and other covariates. There was no association between OSA and HPV/HR-HPV infection. CONCLUSION: The study underscores the complex relationship between sleep duration and HPV infection risk, suggesting both very short and very long sleep durations may increase HPV infection likelihood. The findings highlight the need for further research to explore the biological mechanisms underpinning this association and to consider broader population groups and more precise sleep assessment methods in future studies.

ATP Concentration-Dependent Fractions of One-Head-Bound and Two-Head-Bound States of the Kinesin Motor during Its Chemomechanical Coupling Cycle.

Kinesin is a typical motor protein that can use the chemical energy of ATP hydrolysis to step processively on microtubules, alternating between one-head-bound and two-head-bound states. Some published experimental results showed that the duration of the one-head-bound state increases greatly with a decrease in ATP concentration, whereas the duration of the two-head-bound state is independent of ATP concentration, indicating that ATP binding occurs in the one-head-bound state. On the contrary, other experimental results showed that the duration of the two-head-bound state increases greatly with a decrease in ATP concentration, whereas the duration of the one-head-bound state increases slightly with a decrease in ATP concentration, indicating that ATP binding occurs mainly in the two-head-bound state. Here, we explain consistently and quantitatively these contradictory experimental results, resolving the controversy that is critical to the chemomechanical coupling mechanism of the kinesin motor.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis.

Emerging evidence has figured that serum conversion rate of mumps is a crucial link of mumps disease. Nevertheless, a rising number of mumps outbreaks caused our attention and studies examining the serum conversion cases were conducted in small samples previously; this meta-analysis was conducted to assess the immunogenicity and safety of a mumps containing vaccine (MuCV) before 2019. We identified a total of 17 studies from the year of 2002-2017. In the case-control studies, the vaccine effectiveness (VE) of MuCV in preventing laboratory-confirmed mumps was 68% (odds risk: 0.32; 95% confidence interval [CI], 0.14-0.70) while in the cohort studies and randomised control trials, 58% (relative risk [RR]: 0.42; 95% CI, 0.26-0.69). Similar intervals of effectiveness rates were found during non-outbreak periods compared with outbreak periods (VE: 66%; RR: 0.34; 95% CI, 0.18-0.68 versus VE: 49%; RR: 0.51; 95% CI, 0.21-1.27). In addition, the MuCV group with two and three doses did not show enhanced laboratory-confirmed mumps than one dose (VE: 58%; RR: 0.42; 95% CI, 0.20-0.88 versus VE: 65%, RR: 0.35; 95% CI, 0.20-0.61) for the reason of the overlap of 95% CI. MuCV had comparable effectiveness comparing non-outbreak and outbreak period, one dose, and two or three doses. MuCV displayed acceptable adverse event profiles.

Surgical tumor-derived nanoplatform targets tumor-associated macrophage for personalized postsurgical cancer immunotherapy.

Directly activating CD8+ T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8+ T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor-derived galactose ligand-modified cancer cell membrane (CM)-coated cysteine protease inhibitor (E64)-loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy. The platform targeted M2-like TAMs and released E64 within lysosomes, which reshaped antigen cross-presentation and directly activated CD8+ T cells, thus suppressing B16-OVA melanoma growth. Furthermore, this platform, in combination with anti-PD-L1 antibodies, enhanced the therapeutic efficacy and substantially inhibited 4T1 tumor growth. CMs obtained from surgically resected tumors were used to construct a personalized nanotherapeutic platform, which, in synergy with immune checkpoint blockade (ICB), effectively inhibited postsurgical tumor recurrence in 4T1 tumor. Our work offered a robust, safe strategy for cancer immunotherapy and prevention of postsurgical tumor recurrence.

STCGRU: A hybrid model based on CNN and BiGRU for mild cognitive impairment diagnosis.

BACKGROUND AND OBJECTIVE: Early diagnosis of mild cognitive impairment (MCI) is one of the essential measures to prevent its further development into Alzheimer's disease (AD). In this paper, we propose a hybrid deep learning model for early diagnosis of MCI, called spatio-temporal convolutional gated recurrent unit network (STCGRU). METHODS: The STCGRU comprises three bespoke convolutional neural network (CNN) modules and a bi-directional gated recurrent unit (BiGRU) module, which can effectively extract the spatial and temporal features of EEG and obtain excellent diagnostic results. We use a publicly available EEG dataset that has not undergone pre-processing to verify the robustness and accuracy of the model. Ablation experiments on STCGRU are conducted to showcase the individual performance improvement of each module. RESULTS: Compared with other state-of-the-art approaches using the same publicly available EEG dataset, the results show that STCGRU is more suitable for early diagnosis of MCI. After 10-fold cross-validation, the average classification accuracy of the hybrid model reached 99.95 %, while the average kappa value reached 0.9989. CONCLUSIONS: The experimental results show that the hybrid model proposed in this paper can directly extract compelling spatio-temporal features from the raw EEG data for classification. The STCGRU allows for accurate diagnosis of patients with MCI and has a high practical value.

CD8+ T cells sustain antitumor response by mediating crosstalk between adenosine A2A receptor and glutathione/GPX4.

Antitumor responses of CD8+ T cells are tightly regulated by distinct metabolic fitness. High levels of glutathione (GSH) are observed in the majority of tumors, contributing to cancer progression and treatment resistance in part by preventing glutathione peroxidase 4-dependent (GPX4-dependent) ferroptosis. Here, we show the necessity of adenosine A2A receptor (A2AR) signaling and the GSH/GPX4 axis in orchestrating metabolic fitness and survival of functionally competent CD8+ T cells. Activated CD8+ T cells treated ex vivo with simultaneous inhibition of A2AR and lipid peroxidation acquire a superior capacity to proliferate and persist in vivo, demonstrating a translatable means to prevent ferroptosis in adoptive cell therapy. Additionally, we identify a particular cluster of intratumoral CD8+ T cells expressing a putative gene signature of GSH metabolism (GMGS) in association with clinical response and survival across several human cancers. Our study addresses a key role of GSH/GPX4 and adenosinergic pathways in fine-tuning the metabolic fitness of antitumor CD8+ T cells.

Pharmacological suppression of the OTUD4-CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers.

Despite widespread utilization of immunotherapy, challenge to treat immune-cold tumors needs to be resolved. Multiomic analyses and experimental validation identified the OTUD4-CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization that inhibits tumor immune responses. We further demonstrated the importance of TGF-ß signaling for orchestrating the OTUD4-CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic CD8+ T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-L1 therapy. Collectively, our findings uncover a novel strategy for targeting immunosuppressive OTUD4-CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Human lens epithelial-secreted exosomes attenuate ocular angiogenesis via inhibiting microglial activation.

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.

Construction of a prognostic prediction model in liver cancer based on genes involved in integrin cell surface interactions pathway by multi-omics screening.

Background: Liver cancer is a common malignant tumor with an increasing incidence in recent years. We aimed to develop a model by integrating clinical information and multi-omics profiles of genes to predict survival of patients with liver cancer. Methods: The multi-omics data were integrated to identify liver cancer survival-associated signal pathways. Then, a prognostic risk score model was established based on key genes in a specific pathway, followed by the analysis of the relationship between the risk score and clinical features as well as molecular and immunologic characterization of the key genes included in the prediction model. The function experiments were performed to further elucidate the undergoing molecular mechanism. Results: Totally, 4 pathways associated with liver cancer patients' survival were identified. In the pathway of integrin cell surface interactions, low expression of COMP and SPP1, and low CNVs level of COL4A2 and ITGAV were significantly related to prognosis. Based on above 4 genes, the risk score model for prognosis was established. Risk score, ITGAV and SPP1 were the most significantly positively related to activated dendritic cell. COL4A2 and COMP were the most significantly positively associated with Type 1 T helper cell and regulatory T cell, respectively. The nomogram (involved T stage and risk score) may better predict short-term survival. The cell assay showed that overexpression of ITGAV promoted tumorigenesis. Conclusion: The risk score model constructed with four genes (COMP, SPP1, COL4A2, and ITGAV) may be used to predict survival in liver cancer patients.

Facile synthesis of NiCoSe2@carbon anode for high-performance sodium-ion batteries.

Sodium-ion batteries offer significant advantages in terms of low-temperature performance and safety. In this study, we present a straightforward synthetic approach to produce bimetallic selenide NiCoSe2 nanoparticles grown on a three-dimensional porous carbon framework for application as anode materials in sodium-ion batteries. This unique architecture enhances reaction kinetics and structural stability. The three-dimensional interconnected porous carbon network establishes a continuous pathway of electronic conductive, while increasing specific surface area and mitigating volume expansion. Consequently, these features expedite ion transfer and enhance electrolyte interaction. Notably, compared to CoSe, NiCoSe2 exhibits reduced ion transport distances and lower sodium diffusion barriers. Leveraging these attributes, NiCoSe2/N, Se co-doped carbon composite materials (NiCoSe2/NSC) demonstrate a high specific capacity of 320.8 mAh/g, even after 1000 cycles at 5.0 A/g, with a capacity retention rate of 85.1%. The study further delves into the revelation of the reaction mechanism and ion transport pathway through in-situ X-ray diffraction (XRD) analysis and theoretical calculations. The development of these anode materials is poised to pave the way for advancements in sodium-ion battery technology.

High CD204+ tumor-associated macrophage density predicts a poor prognosis in patients with clear cell renal cell carcinoma.

Purpose: Tumor-associated macrophages (TAMs) play a crucial role in solid tumors and display varying characteristics depending on the specific tumor microenvironment (TME). The study investigated the presence and characteristics of TAMs in renal clear cell carcinoma (ccRCC) and assessed their influence on patient prognosis. Methods: Immunohistochemistry (IHC) was used to identify CD204+ TAMs in a cohort of 72 patients with ccRCC. Kaplan-Meier survival analysis and log-rank test were used to evaluate the prognostic significance of CD204+ TAMs in each group. The TCGA-KIRC cohort was used to analyze the relationship between CD204 and immunity. The functions of CD204+ TAMs in the TCGA-KIRC cohort were analyzed through GO enrichment analysis. Immunofluorescence (IF) was conducted to confirm the positive effects of CD204 on regulatory T (Treg) cells and exhausted T (Tex) cells. Results: There was a negative relation between high infiltration of CD204+ TAMs and both overall survival (OS) and progression-free survival (PFS) in ccRCC. A positive correlation was found between high-infiltrating CD204+ TAMs and distant organ metastasis, as well as lymph node metastasis. In the TCGA-KIRC cohort, the group with high expression of CD204 exhibited significant up-regulation of 120 genes as well as enrichment in the negative regulation of immunity. CD204 high-expression group showed up-regulation of Treg cells and Tex cells. Conclusion: The presence of CD204+ TAMs in ccRCC is associated with a negative prognosis in patients. The high infiltration of CD204 promotes distant organ metastasis by aggerating Treg cells and Tex cells.

Differential evaluation of sulfur oxides in the natural lake water samples by carbazole-furan fluorescent probe.

Water bodies are frequently polluted, with sulfur oxides being the most common form of water pollution. Therefore, developing a detection mechanism for sulfur oxides in water bodies is particularly urgent. A new fluorescent probe YX-KZBD was designed and developed. This probe releases fluorescent signals with its own sulfurous acid recognition site, detects sulfurous acid based on the Michael addition reaction, and evaluates the pollution degree of sulfur oxides in the water environment through the transformation mode of the sulfur cycle. This probe has high energy transfer efficiency in aqueous solutions. In addition, the fluorescence data obtained by analyzing the water samples were linearly fitted with the gene abundance values of the functional genes of sulfur-producing bacteria, and a significant correlation was obtained. The Kriging interpolation model was used to evaluate the sulfate content distribution at each sampling point to understand the distribution of sulfur oxides in natural water intuitively. The fluorescence signal excited by the probe was also combined with a real-time quantitative polymerase chain reaction (qPCR), and sulfate-reducing and sulfur-oxidizing bacteria were introduced in the sulfur cycle, providing a new method to assess the extent of water pollution effectively.

Computational Studies Reveal How Passive Cross-Linkers Regulate Anaphase Spindle Elongation.

In eukaryotic cell division, a series of events are organized to produce two daughter cells. The spindle elongation in anaphase B is essential for providing enough space to maintain cell size and distribute sister chromatids properly, which is associated with microtubules and microtubule-associated proteins such as kinesin-5 Eg5 and the Ase1-related protein, PRC1. The available experimental data indicated that after the start of anaphase B more PRC1 proteins can bind to the antiparallel microtubule pairs in the spindle but the excess amount of PRC1 proteins can lead to the failure of cell division, indicating that PRC1 proteins can regulate the spindle elongation in a concentration-dependent manner. However, the underlying mechanism of the PRC1 proteins regulating the spindle elongation has not been explained up to now. Here, we use a simplified model, where only the two important participants (kinesin-5 Eg5 motors and PRC1 proteins) are considered, to study the spindle elongation during anaphase B. We first show that only in the appropriate range of the PRC1 concentration can the spindle elongation complete properly. Furthermore, we explore the underlying mechanism of PRC1 as a regulator for spindle elongation.

p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome.

Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome.