Manipulating the tumour immune microenvironment by N6-methyladenosine RNA modification.

N6-methyladenosine (m6A), a posttranscriptional regulatory mechanism, is the most common epigenetic modification in mammalian mRNA. M6A modifications play a crucial role in the developmental network of immune cells. The expression of m6A-related regulators often affects carcinogenesis and tumour suppression networks. In the tumour microenvironment, m6A-modified enzymes can affect the occurrence and progression of tumours by regulating the activation and invasion of tumour-associated immune cells. Immunotherapy, which utilises immune cells, has been demonstrated to be a powerful weapon in tumour treatment and is increasingly being used in the clinic. Here, we provide an updated and comprehensive overview of how m6A modifications affect invasive immune cells and their potential role in immune regulation. In addition, we summarise the regulation of epigenetic regulators associated with m6A modifications in tumour cells on the antitumour response of immune cells in the tumour immune microenvironment. These findings provide new insights into the role of m6A modifications in the immune response and tumour development, leading to the development of novel immunotherapies for cancer treatment.

Establishment and validation of an artificial intelligence web application for predicting postoperative in-hospital mortality in patients with hip fracture: a National cohort study of 52,707 cases.

BACKGROUND: In-hospital mortality following hip fractures is a significant concern, and accurate prediction of this outcome is crucial for appropriate clinical management. Nonetheless, there is a lack of effective prediction tools in clinical practice. By utilizing artificial intelligence and machine learning techniques, this study aims to develop a predictive model that can assist clinicians in identifying geriatric hip fracture patients at a higher risk of in-hospital mortality. METHODS: A total of 52,707 geriatric hip fracture patients treated with surgery from 90 hospitals were included in this study. The primary outcome was postoperative in-hospital mortality. The patients were randomly divided into two groups, with a ratio of 7:3. The majority of patients, assigned to the training cohort, were used to develop the AI models. The remaining patients, assigned to the validation cohort, were used to validate the models. Various machine learning algorithms, including logistic regression (LR), decision tree (DT), naïve Bayesian (NB), neural network (NN), eXGBoosting machine (eXGBM), and random forest (RF), were employed for model development. A comprehensive scoring system, incorporating 10 evaluation metrics, was developed to assess the prediction performance, with higher scores indicating superior predictive capability. Based on the best machine learning-based model, an AI application was developed on the Internet. In addition, a comparative testing of prediction performance between doctors and the AI application. FINDINGS: The eXGBM model exhibited the best prediction performance, with an AUC of 0.908 (95% CI: 0.881-0.932), as well as the highest accuracy (0.820), precision (0.817), specificity (0.814), and F1 score (0.822), and the lowest Brier score (0.120) and log loss (0.374). Additionally, the model showed favorable calibration, with a slope of 0.999 and an intercept of 0.028. According to the scoring system incorporating 10 evaluation metrics, the eXGBM model achieved the highest score (56), followed by the RF model (48) and NN model (41). The LR, DT, and NB models had total scores of 27, 30, and 13, respectively. The AI application has been deployed online at https://in-hospitaldeathinhipfracture-l9vhqo3l55fy8dkdvuskvu.streamlit.app/ , based on the eXGBM model. The comparative testing revealed that the AI application's predictive capabilities significantly outperformed those of the doctors in terms of AUC values (0.908 vs. 0.682, P <0.001). CONCLUSIONS: The eXGBM model demonstrates promising predictive performance in assessing the risk of postoperative in-hospital mortality among geriatric hip fracture patients. The developed AI model serves as a valuable tool to enhance clinical decision-making.

Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.

Chemotherapy resistance is a common cause of tumor treatment failure. Various molecular responses, such as increased expression of efflux transporter proteins, including Pglycoprotein (P-gp), changes in the tumor microenvironment (TME), the role of platelets, and the effects of cancer stem cells (CSCs), can lead to drug resistance. Through extensive research on the mechanisms of drug resistance, more effective anti-resistance drugs and therapeutic approaches are being developed. This review explores drug resistance mechanisms and summarizes relevant anti-resistance drugs. In addition, due to the therapeutic limitations of the aforementioned treatments, new advances in nanocarrier-based combination immunotherapy to address the challenge of drug resistance have been described. Nanocarriers combined with immunotherapy can not only target tumor sites for targeted drug release but also modulate the autoimmune system and enhance immune efficacy, thereby overcoming tumor drug resistance. This review suggests new strategies for overcoming tumor drug resistance and is expected to inform tumor treatment and prognosis.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

Mediastinal epithelioid inflammatory myofibroblastic sarcoma with the EML4-ALK fusion: A case report and literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumour which rarely affects the chest cavity. We, for the first time, report a case of mediastinal EIMS with the EML4-ALK fusion. A young woman presented to our hospital with cough, chest tightness and shortness of breath. Computed tomography (CT) showed a mixed attenuation soft-tissue mass in the right middle and upper mediastinum. Negative results were obtained from bronchoscopy forceps biopsy and endobronchial ultrasound-guided transbronchial fine needle aspiration. CT-guided percutaneous biopsy was finally performed. However, due to the rapidly progressed EIMS that compressed the trachea and right main bronchus, the patient died of respiratory failure 1 day before diagnosis. EIMS progresses rapidly, and an early diagnosis is important. For mediastinal EIMS, CT-guided percutaneous biopsy may be useful. Next-generation sequencing of blood may be instructive to EIMS patients who are intolerant to invasive biopsy.

Morphologically transformable peptide nanocarriers coloaded with doxorubicin and curcumin inhibit the growth and metastasis of hepatocellular carcinoma.

In tumor treatment, the highly disordered vascular system and lack of accumulation of chemotherapeutic drugs in tumors severely limit the therapeutic role of nanocarriers. Smaller drug-containing nanoparticles (NPs) can better penetrate the tumor but are easily removed, which severely limits the tumor-killing properties of the drug. The chemotherapeutic medication doxorubicin (DOX) is highly toxic to the heart, but this toxicity can be effectively mitigated and the combined anticancer effect can be enhanced by clinically incorporating curcumin (CUR) as part of the dual therapy. We designed a small-molecule peptide, Pep1, containing a targeting peptide (CREKA) and a pH-responsive moiety. These NPs can target the blood vessels in tumor microthrombi and undergo a morphological shift in the tumor microenvironment. This process enhances the penetration and accumulation of drugs, ultimately improving the effectiveness of cancer treatment. In vitro and in vivo experiments demonstrated that this morphological transformation allowed rapid and effective drug release into tumors, the effective inhibition of tumor angiogenesis, and the promotion of tumor cell apoptosis, thus effectively killing tumor cells. Our findings provide a novel and simple approach to nhibit the growth and metastasis of hepatocellular carcinoma.

HIF-1α inhibition in macrophages preserves acute liver failure by reducing IL-1ß production.

The development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high-frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages is promoted by both oxygen-dependent and oxygen-independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin-1ß (IL-1ß). IL-1ß further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL-1R) on hepatocyte. HIF-1α knockout in macrophages or IL-1R knockout in hepatocytes protects against liver failure. However, whether HIF-1α inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF-1α inhibitor PX-478 inhibits the expression and secretion of IL-1ß, but not tumor necrosis factor α (TNFα), in bone marrow-derived macrophages (BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN-induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX-478 combined with TNFα neutralizing antibody markedly improved LPS/D-GalN-induced ALF. Taken together, our data suggest that PX-478 administration leads to HIF-1α inhibition and decreased IL-1ß secretion in macrophages, which represents a promising therapeutic strategy for inflammation-induced ALF.

Validation of the KangarooSci® Aerobic Count Plate for the Enumeration of Meosphilic Aerobic Bacteria in Selected Foods and on Stainless Steel Environmental Surfaces: AOAC Performance Tested MethodSM 062301.

BACKGROUND: The KangarooSci® Aerobic Count Plate (ACP) is a sample-ready culture medium system for direct counting of aerobic bacteria colonies after 48-72 h of incubation. OBJECTIVE: The KangarooSci ACP was evaluated for AOAC Performance Tested MethodsSM certification. METHODS: The KangarooSci ACP was evaluated through matrix studies and product consistency/stability study and robustness testing. For the matrix study, nine food products (nonfat dry milk powder, fresh raw bovine milk, pasteurized liquid bovine milk, fresh raw ground beef, frozen uncooked chicken breast, cooked shredded pork, apple juice, ice cream, and fresh strawberries), and one environmental surface (stainless steel) were evaluated following the KangarooSci ACP product instructions and compared to the ISO 4833-1:2013, Microbiology of food and animal feeding stuffs-Horizontal methods for the enumeration of microorganisms-Part 1: Colony count at 30 °C by the pour plate technique reference standard. The product consistency and stability testing evaluated three separate production lots of the KangarooSci ACP. The robustness testing examined three test parameters, volume of sample plated, incubation time, and incubation temperature, using a factorial study design. RESULTS: Results from the matrix study demonstrated equivalent performance between the KangarooSci ACP and the ISO 4833-1:2013 reference standard. The product consistency and stability testing showed that the performance of the assay was equivalent over time up to 12 months and between production lots. Minor changes to the operational test conditions showed no significant impact on performance during the robustness testing. CONCLUSION: The KangarooSci ACP is an effective method for aerobic plate count for all matrixes evaluated. HIGHLIGHTS: The KangarooSci ACP allows for fast, reliable enumeration of aerobic bacteria. Utilizing the alternative method takes up less space in incubators, requires no sample spreader, and requires fewer consumables compared to the reference method.

Unsupervised dimensionality reduction of medical hyperspectral imagery in tensor space.

BACKGROUND AND OBJECTIVES: Compared with traditional RGB images, medical hyperspectral imagery (HSI) has numerous continuous narrow spectral bands, which can provide rich information for cancer diagnosis. However, the abundant spectral bands also contain a large amount of redundancy information and increase computational complexity. Thus, dimensionality reduction (DR) is essential in HSI analysis. All vector-based DR methods ignore the cubic nature of HSI resulting from vectorization. To overcome the disadvantage of vector-based DR methods, tensor-based techniques have been developed by employing multi-linear algebra. METHODS: To fully exploit the structure features of medical HSI and enhance computational efficiency, a novel method called unsupervised dimensionality reduction via tensor-based low-rank collaborative graph embedding (TLCGE) is proposed. TLCGE introduces entropy rate superpixel (ERS) segmentation algorithm to generate superpixels. Then, a low-rank collaborative graph weight matrix is constructed on each superpixel, greatly improving the efficiency and robustness of the proposed method. After that, TLCGE reduces dimensions in tensor space to well preserve intrinsic structure of HSI. RESULTS: The proposed TLCGE is tested on cholangiocarcinoma microscopic hyperspectral data sets. To further demonstrate the effectiveness of the proposed algorithm, other machine learning DR methods are used for comparison. Experimental results on cholangiocarcinoma microscopic hyperspectral data sets validate the effectiveness of the proposed TLCGE. CONCLUSIONS: The proposed TLCGE is a tensor-based DR method, which can maintain the intrinsic 3-D data structure of medical HSI. By imposing the low-rank and sparse constraints on the objective function, the proposed TLCGE can fully explore the local and global structures within each superpixel. The computational efficiency of the proposed TLCGE is better than other tensor-based DR methods, which can be used as a preprocessing step in real medical HSI classification or segmentation.

Emerging roles of circ_NRIP1 in tumor development and cancer therapy (Review).

Circular RNA (circRNA) is a class of endogenous non-coding RNA, a type of single-stranded covalently closed RNA molecule formed by alternative splicing of exons or introns. Previous studies have demonstrated that circRNA participates in modulating biological processes such as cell proliferation, differentiation and apoptosis, and plays key roles in tumor occurrence and development. CircRNA nuclear receptor interacting protein 1 (circ_NRIP1), a form of circRNA, is abnormally expressed in certain human tumor types. It is present at a higher abundance compared with cognate linear transcripts and can regulate malignant biological behaviors such as tumor proliferation, invasion and migration, revealing a currently unexplored frontier in cancer progression. The present review presents a pattern of circ_NRIP1 expression in various malignant tumor types and highlights its significance in cancer development, in addition to its potential as a disease indicator or future therapeutic agent.

RNA N6-methyladenosine (m6A) modification in HNSCC: molecular mechanism and therapeutic potential.

Head and neck squamous cell carcinoma ranks seventh in incidence of malignant tumours in the world. Although there are treatments including surgery, radiotherapy and chemotherapy, targeted therapy and immunotherapy, drug resistance to treatment is caused by various reasons, and the survival rate of patients remains frustrating. To overcome the bottleneck of treatment at this stage, it is urgent to identify possible diagnostic and prognostic markers. N6-methyladenosine is a methylation modification on the sixth N atom of adenine which is the most abundant epitope transcriptome modification in mammalian genes. N6-methyladenosine modification is reversible and results from the interaction among writers, erasers and readers. A large number of studies have proven that N6-methyladenosine modification has important significance in promoting the progression and treatment of tumours and have made great progress in research. In this review, we introduce how N6-methyladenosine modification promotes the occurrence and development of tumours, the mechanism of drug resistance, and new findings of N6-methyladenosine modification in radiotherapy and chemotherapy, immunotherapy, and targeted therapy. N6-methyladenosine modification provides more possibilities for improving the overall survival rate and prognosis of patients.

Multiplexed optical fiber cell temperature sensing system with high sensitivity and accuracy.

Significance: A multiplexed fiber laser sensing system for cell temperature is proposed. To the best of the authors' knowledge, this is the first multilongitudinal mode (MLM) optical fiber laser sensor array designed for cell temperature sensing. Aim: A two-channel cell temperature sensing system with high sensitivity and real-time sensing capability is achieved. The temperature change of human hepatoellular carcinomas (HepG2) cells under the influence of exogenous chemical aflatoxin B1 (AFB1) can be monitored in real time. Approach: A fiber laser cavity consists of a pair of fiber Bragg gratings (FBGs) with matched central wavelengths and a piece of erbium-doped fiber (EDF). The static FBG is utilized for design of fiber laser cavity and laser modes selection. In comparison, the sensing FBG is used for cell temperature sensing. The sensing FBG has a length of 10 mm and a diameter of 200 µ m . Beat frequency signals (BFS) are generated by MLM lasers after optical-to-electrical conversion at a photodetector. Frequency change of a BFS is closely related to the reflected wavelength change of the sensing FBG. Through frequency division multiplexing, two fiber laser cavities are designed in the sensing system for two-channel temperature sensing. Frequency shift of a BFS that represents temperature change of cells can be automatically recorded in seconds. Results: A two-channel cell temperature sensing system is designed with high sensitivities of 101.62 and 119.82 kHz / ° C , respectively. The temperature change of HepG2 cells under the influence of exogenous chemical AFB1 is monitored in real time. Conclusions: The proposed system has the advantages of simple structure, high sensitivity, and two-channel sensing capability. Our study provides a simple and effective method to design a fiber laser sensor system without complex demodulation techniques and expensive optical components.

Sensitive Electrochemical Sensor for Glycoprotein Detection Using a Self-Serviced-Track 3D DNA Walker and Catalytic Hairpin Assembly Enzyme-Free Signal Amplification.

Approaches for the detection of targets in the cellular microenvironment have been extensively developed. However, developing a method with sensitive and accurate analysis for noninvasive cancer diagnosis has remained challenging until now. Here, we reported a sensitive and universal electrochemical platform that integrates a self-serviced-track 3D DNA walker and catalytic hairpin assembly (CHA) triggering G-Quadruplex/Hemin DNAzyme assembly signal amplification. In the presence of a target, the aptamer recognition initiated the 3D DNA walker on the cell surface autonomous running and releasing DNA (C) from the triple helix. The released DNA C as the target-triggered CHA moiety, and then G-quadruplex/hemin, was formed on the surface of electrode. Eventually, a large amount of G-quadruplex/hemin was formed on the sensor surface to generate an amplified electrochemical signal. Using N-acetylgalactosamine as a model, benefiting from the high selectivity and sensitivity of the self-serviced-track 3D DNA walker and the CHA, this designed method showed a detection limit of 39 cell/mL and 2.16 nM N-acetylgalactosamine. Furthermore, this detection strategy was enzyme free and exhibited highly sensitive, accurate, and universal detection of a variety of targets by using the corresponding DNA aptamer in clinical sample analysis, showing potential for early and prognostic diagnostic application.

Identification of a Hypoxia-Related Signature as Candidate Detector for Schizophrenia Based on Genome-Wide Gene Expression.

INTRODUCTION: Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients. METHODS: GSE17612, GSE21935, and GSE53987 datasets, consisting of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patient. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores and patients in low-score groups if their hypoxia score was in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients. RESULTS: In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in the patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients. CONCLUSION: These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.

Metabolic pathway-based self-assembled Au@MXene liver microsome electrochemical biosensor for rapid screening of aflatoxin B1.

Cytochrome P450 enzymes (CYPs) catalyze the production of aflatoxin B1 (AFB1) metabolites, which play an important role in carcinogenesis. In this study, we report a simple electrochemical liver-microsome-based biosensor using a composite of gold nanoparticles adsorbed on MXene (Au@MXene) for rapid screening of AFB1. Rat liver microsomes (RLMs) were directly adsorbed on the Au@MXene nanocomposite. The high conductivity, large specific surface area, and good biocompatibility of the Au@MXene nanocomposite enabled the direct electron transfer between the RLMs and the electrode and maintained the biological activity of the enzyme in the RLMs to a large extent. The metabolic behavior of the RLM biosensor that was developed for the electrocatalyst of AFB1 to its hydroxylation metabolite aflatoxin M1 (AFM1) was confirmed. Based on the change in the electrical signal generated by this metabolic behavior, we established the relationship between AFB1 content and amperometric (I-t) current signal. When the AFB1 concentration ranged from 0.01 µM to 50 µM, the AFB1 concentration was linearly related to the electrical signal with a limit of detection of 2.8 nM. The results of the recovery experiments for corn samples showed that the recovery and accuracy of the sensor were consistent with the UPLC-MS/MS method.

Tris(bipyridine)ruthenium(II)-functionalized metal-organic frameworks for the ratiometric fluorescence determination of aluminum ions.

A novel ratiometric fluorescence probe was designed for the determination of Al3+ by self-assembling of NH2-MIL-101(Fe) and [Ru(bpy)3]2+. Under the excitation wavelength of 360 nm, the NH2-MIL-101(Fe)@[Ru(bpy)3]2+ presented a dual-emitting luminescent property at 440 and 605 nm, respectively. In the presence of Al3+, the blue fluorescence of NH2-MIL-101(Fe)@[Ru(bpy)3]2+ at 440 nm was enhanced remarkably, while the red emission at 605 nm was almost not influenced. Therefore, taking the fluorescence at 440 nm as the report signal and 605 nm as the reference signal, quantitative determination was achieved for Al3+ concentration in the ranges 0.2-25 µM and 25-250 µM. The limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 73 nM and 244 nM, respectively. The sensing mechanisms were studied by theoretical calculation and optical spectra. The analysis of real food samples confirmed the suitability of the proposed method. More importantly, portable fluorescent test papers were successfully manufactured to provide a strategy for visual, rapid, and on-site detection of Al3+.

ROS generation strategy based on biomimetic nanosheets by self-assembly of nanozymes.

Reactive oxygen species (ROS) play an important role in physiology and have been applied in tumor therapy. However, insufficient endogenous H2O2 and hypoxia in cancer cells can lead to limited ROS production and poor therapeutic efficacy. Herein, we develop a biomimetic nanosheet material based on the self-assembly of nanozymes that could supply H2O2 under acidic conditions and catalyze a cascade of intracellular biochemical reactions to produce ROS under both normoxic and hypoxic conditions without any external stimuli. In this system, the copper peroxide nanosheets (CPNS), which are pH-responsive, were prepared through coordination of H2O2 to Cu2+ and then modified using ultrafine Pt NPs to form CPNS@Pt. The CPNS could decompose under acidic conditions, allowing the simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. On the other hand, Pt NPs were also released. The released Pt NPs behave as an oxidase mimic and catalase mimic. In this way, the well-defined CPNS@Pt can not only relieve hypoxic conditions but also generate ROS to induce cell apoptosis, thereby paving the way for the development of a nanozyme with multienzyme activity as a therapeutic strategy.

Prognostic Value of the Geriatric Nutritional Risk Index in Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

This study aimed to quantitatively identify the prognostic and clinicopathological value of the geriatric nutritional risk index (GNRI) in non-small cell lung cancer (NSCLC) through a meta-analysis. The electronic databases PubMed, Web of Science, Embase, and Cochrane Library were thoroughly searched from inception to December 14, 2021. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic value of GNRI. Odds ratios (ORs) and 95%CIs were combined to estimate the clinicopathological significance of the GNRI in NSCLC. Seven studies with 2,023 patients were included in the meta-analysis. A low GNRI score was significantly associated with poor overall survival (OS) (HR = 2.01, 95%CI = 1.65-2.44, p < 0.001) and worse progression-free survival (PFS), recurrence-free survival (RFS), and cancer-specific survival (CSS) (HR = 1.81, 95%CI = 1.48-2.22, p < 0.001) in NSCLC. Furthermore, a low GNRI score was significantly associated with the histological type of non-adenocarcinoma (OR= 1.55, 95%CI = 1.19-2.03, p = 0.001) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (OR= 2.81, 95%CI= 1.49-5.32, p = 0.001). A low GNRI score is a significant and effective prognostic marker for poor survival outcomes in patients with NSCLC. In addition, low GNRI score was correlated with higher ECOG PS scores.

Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women.

INTRODUCTION: Variants in the tau gene (MAPT) region are associated with breast cancer in women and Alzheimer's disease (AD) among persons lacking apolipoprotein E ε4 (ε4-). METHODS: To identify novel genes associated with tau-related pathology, we conducted two genome-wide association studies (GWAS) for AD, one among 10,340 ε4- women in the Alzheimer's Disease Genetics Consortium (ADGC) and another in 31 members (22 women) of a consanguineous Hutterite kindred. RESULTS: We identified novel associations of AD with MGMT variants in the ADGC (rs12775171, odds ratio [OR] = 1.4, P = 4.9 × 10-8 ) and Hutterite (rs12256016 and rs2803456, OR = 2.0, P = 1.9 × 10-14 ) datasets. Multi-omics analyses showed that the most significant and largest number of associations among the single nucleotide polymorphisms (SNPs), DNA-methylated CpGs, MGMT expression, and AD-related neuropathological traits were observed among women. Furthermore, promoter capture Hi-C analyses revealed long-range interactions of the MGMT promoter with MGMT SNPs and CpG sites. DISCUSSION: These findings suggest that epigenetically regulated MGMT expression is involved in AD pathogenesis, especially in women.

Versatile metal-organic frameworks as a catalyst and an indicator of nitric oxide.

The imaging of nitric oxide (NO) and its donors is crucial to explore NO-related physiological and pathological processes. In this work, we demonstrate the use of Cu-based metal-organic frameworks (Cu-MOFs) as nanoprobes for NO detection and as a catalyst for the generation of NO from the biologically occurring substrate, S-nitrosothiols (RSNOs). The paramagnetic Cu2+ in the MOFs could quench the luminescence of triphenylamine; Cu-MOFs only exhibited weak emission at 450 nm. Upon the addition of NO, the paramagnetic Cu2+ was reduced to diamagnetic Cu+, and thus the luminescence was recovered directly. Cu-MOFs exhibited high selectivity for other species in the reaction system, including NO2-, H2O2, AA, NO3- and 1O2. More significantly, the Cu+ can react with s-nitrosoglutathione (GSNO), s-nitrosocysteine (CysNO), and s-nitrosocysteamine (CysamNO) to generate NO and then oxidize to Cu2+-MOFs with quenched luminescence, respectively, and thus the catalysis is inhibited, noted as a self-controlled process. The Cu-MOFs catalyst was confirmed by powder X-ray diffraction to remain structurally intact in aqueous environments. The Cu-MOFs have been successfully employed in the biological imaging of NO in living cells. The bifunctional MOFs could offer a novel platform for the real-time monitoring of NO species, provide potential for exploiting NO in cancer therapy and improve the methodologies to elucidate the NO-related biological processes.