A novel prognostic risk-scoring system based on m5C methylation regulator-mediated patterns for glioma patients.

N5-methylcytosine (m5C) methylation modification plays a crucial role in the epigenetic mechanisms underlying tumorigenesis, aggressiveness, and malignancy in diffuse glioma. Our study aimed to develop a novel prognostic risk-scoring system to assess the impact of m5C modification in glioma patients. Initially, we identified two distinct m5C clusters based on the expression level of m5C regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two m5C cluster groups were determined. Utilizing these m5C regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an m5C scoring system was developed through a univariate Cox regression model, quantifying the m5C modification patterns utilizing six DEGs associated with disease prognosis. The resulting scoring system allowed us to categorize patients into high- or low-risk groups based on their m5C scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher m5C score consistently exhibited shorter survival durations, fewer isocitrate dehydrogenase (IDH) mutations, less 1p/19q codeletion and higher World Health Organization (WHO) grades. Additionally, distinct immune cell infiltration characteristics were observed among different m5C cluster groups and risk groups. Our study developed a novel prognostic scoring system based on m5C modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.

Resistant Starch from Purple Sweet Potatoes Alleviates Dextran Sulfate Sodium-Induced Colitis through Modulating the Homeostasis of the Gut Microbiota.

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1ß, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

A synergistic strategy based on active hydroxymethyl amine compounds and fucoidan for bioprosthetic heart valves with enhancing anti-coagulation and anti-calcification properties.

With an aging population, the patients with valvular heart disease (VHD) are growing worldwide, and valve replacement is a primary choice for these patients with severe valvular disease. Among them, bioprosthetic heart valves (BHVs), especially BHVs trough transcatheter aortic valve replacement, are widely accepted by patients on account of their good hemodynamics and biocompatibility. Commercial BHVs in clinic are prepared by glutaraldehyde cross-linked pericardial tissue with the risk of calcification and thrombotic complications. In the present study, a strategy combines improved hemocompatibility and anti-calcification properties for BHVs has been developed based on a novel non-glutaraldehyde BHV crosslinker hexakis(hydroxymethyl)melamine (HMM) and the anticoagulant fucoidan. Besides the similar mechanical properties and enhanced component stability compared to glutaraldehyde crosslinked PP (G-PP), the fucoidan modified HMM-crosslinked PPs (HMM-Fu-PPs) also exhibit significantly enhanced anticoagulation performance with a 72 % decrease in thrombus weight compared with G-PP in ex-vivo shunt assay, along with the superior biocompatibility, satisfactory anti-calcification properties confirmed by subcutaneous implantation. Owing to good comprehensive performance of these HMM-Fu-PPs, this simple and feasible strategy may offer a great potential for BHV fabrication in the future, and open a new avenue to explore more N-hydroxymethyl compound based crosslinker with excellent performance in the field of biomaterials.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

BACKGROUND: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. METHODS: qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. RESULTS: The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. CONCLUSIONS: The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Distinguishing the Geometric and Electronic Structures of Actinide Carbides AnxC8 (An = Th, U; x = 2, 3) through Exchange Interactions.

Global-minimum optimizations combined with relativistic quantum chemistry calculations have been performed to characterize the ground-state stable structures of four titled compounds and to analyze the bonding properties. Th2C8 was identified as being a ThC4-Th(C2)2 structure, U2C8 has been found to favor the U-U(C8) structure, and both Th3C8 and U3C8 adopt the (AnC3)2-(AnC2) structure. Then, the wave function analyses reveal that the interactions between the Th 7s-based orbital and the σg molecular orbital of the C2 unit compensate for the excitation energy of 7s16d1 → 6d2 and lead to the stabilization of two Th(IV)s in the ThC4-Th(C2)2 structure. It also reveals that the U species exhibit magnetic exchange coupling behavior in UxC8, for instance, as seen in the direct interaction of U2C8 and the superexchange pathway of U3C8, which effectively stabilizes their low-spin states. This interpretation indicates that the geometric and electronic structures of AnxC8 species are largely influenced by the local magnetic moment and spin correlation.

Discovery of novel ß-elemene hybrids with hydrogen sulfide-releasing moiety possessing cardiovascular protective activity for the treatment of atherosclerosis.

Herein, a series of novel ß-elemene hybrids with different types of hydrogen sulfide (H2S) donors was designed and synthesized for the first time. In addition, all compounds were tested for H2S release in phosphate buffer solution assay, among which the derivatives with 5-p-hydroxyphenyl-3H-1,2-dithiole-3-thione (ADT-OH) as the H2S donor released the best level. The results of the isolated vasodilation assay revealed that all the compounds exhibited a degree of vasodilatory effect, and the representative compound "ß-elemene-H2S gas donor" hybrid L13-2h produced more than 50% vasodilatory activity at a concentration of 20 µM. Furthermore, L13-2h possessed good concentration dependence and significantly better vasodilatory activity than the lead compound L13. In the RAW 264.7 cellular lipid inhibition against oxidized low-density lipoprotein (ox-LDL) stimulation assay, eight compounds, including L13-2g and L13-2h, produced significant cellular lipid-lowering activity. The results of the further antioxidant activity study showed that the representative compounds L13-2g and L13-2h improved H2O2-induced oxidative damage in HUVEC cells and compound L13-2h exhibited excellent antioxidant damage protection activity compared to the positive control. Moreover, none of the target compounds appeared to be significantly cytotoxic at the tested concentrations. These results suggest that the hybridization of hydrogen sulfide donors with ß-elemene provides a promising approach for the discovery of novel anti-atherosclerotic drugs from natural products.

A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity.

BACKGROUND: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. METHODS: We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. RESULTS: With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10-2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10-3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. CONCLUSIONS: Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.

Effect of the combination of he-sea and front-mu points on enteral nutrition feeding intolerance in critical illness patients. / åˆå‹Ÿé ç©´æ²»ç–—å±é‡ç—‡æ‚£è€ è‚ å† è¥å »å–‚å »ä¸è€å—çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To explore the effects of the combination of he-sea and front-mu points on the feeding compliance rate, the intra-abdominal pressure, the enteral nutrition tolerance score, the score of acute physiological and chronic health evaluation (APACHE)-Ⅱ and gastrointestinal function impairment grade in the patients with enteral nutrition feeding intolerance (ENFI) of critical illness and evaluate clinical effect on ENFI after acupuncture at the he-sea and front-mu points. METHODS: Seventy patients of ENFI were randomized into a control group and an observation group, 35 cases in each one. In the control group, the patients were treated with routine regimen combined with intestinal nutrition support. In the observation group, on the basis of the treatment as the control group, acupuncture was applied to Shangwan (CV13), Zhongwan (CV12), Xiawan (CV10), Qihai (CV6) and Guanyuan (CV4), as well as bila-teral Neiguan (PC6), Zusanli (ST36), Xiajuxu (ST39), Shangjuxu (ST37), Tianshu (ST25) and Daheng (SP15). Of those acupoints, ST25 and SP15 on the same side were attached to one pair of electrodes (20 Hz/100 Hz). Acupuncture was delivered once daily, 30 min each time and for consecutive 7 days. During treatment, the numbers of the cases up to the feeding standard were observed everyday to calculate the feeding compliance rate. The score of enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of acute gastriointestinal injury(AGI) grading were recorded. RESULTS: After treatment, the enteral feeding compliance rate was increased in comparison with that before treatment in the two groups, and the rate in the observation group was higher than that of the control group (P<0.05) except that on the 2nd day. The score of the enteral nutrition tolerance, the intra-abdominal pressure, the score of APACHE-Ⅱ and the level of AGI were all reduced (P<0.05, P<0.01) when compared with those before treatment in the two groups, and these indicators in the observation group were lower (P<0.05) than those of the control group. CONCLUSIONS: Acupuncture at the he-sea and front-mu points relieves the conditions of ENFI, improves the feeding and the recovery of gastrointestinal function, and benefits the prognosis through increasing the amount of enteral nutrition in ENFI patients.

Gene pyramiding for boosted plant growth and broad abiotic stress tolerance.

Abiotic stresses such as salinity, heat and drought seriously impair plant growth and development, causing a significant loss in crop yield and ornamental value. Biotechnology approaches manipulating specific genes prove to be effective strategies in crop trait modification. The Arabidopsis vacuolar pyrophosphatase gene AVP1, the rice SUMO E3 ligase gene OsSIZ1 and the cyanobacterium flavodoxin gene Fld have previously been implicated in regulating plant stress responses and conferring enhanced tolerance to different abiotic stresses when individually overexpressed in various plant species. We have explored the feasibility of combining multiple favourable traits brought by individual genes to acquire superior plant performance. To this end, we have simultaneously introduced AVP1, OsSIZ1 and Fld in creeping bentgrass. Transgenic (TG) plants overexpressing these three genes performed significantly better than wild type controls and the TGs expressing individual genes under both normal and various abiotic stress conditions, exhibited significantly enhanced plant growth and tolerance to drought, salinity and heat stresses as well as nitrogen and phosphate starvation, which were associated with altered physiological and biochemical characteristics and delicately fine-tuned expression of genes involved in plant stress responses. Our results suggest that AVP1, OsSIZ1 and Fld function synergistically to regulate plant development and plant stress response, leading to superior overall performance under both normal and adverse environments. The information obtained provides new insights into gene stacking as an effective approach for plant genetic engineering. A similar strategy can be extended for the use of other beneficial genes in various crop species for trait modifications, enhancing agricultural production.

Associations between multimorbidity burden and Alzheimer's pathology in older adults without dementia: the CABLE study.

Studies have shown that multimorbidity may be associated with the Alzheimer's disease (AD) stages, but it has not been fully characterized in patients without dementia. A total of 1402 Han Chinese older adults without dementia from Chinese Alzheimer's Biomarker and LifestylE (CABLE) study were included and grouped according to their multimorbidity patterns, defined by the number of chronic disorders and cluster analysis. Multivariable linear regression models were used to detect the associations with AD-related cerebrospinal fluid (CSF) biomarkers. Multimorbidity and severe multimorbidity (≥4 chronic conditions) were significantly associated with CSF amyloid and tau levels (pFDR < 0.05). Metabolic patterns were significantly associated with higher levels of CSF Aß40 (ß = 0.159, pFDR = 0.036) and tau (P-tau: ß = 0.132, pFDR = 0.035; T-tau: ß = 0.126, pFDR = 0.035). The above associations were only significant in the cognitively normal (CN) group. Multimorbidity was associated with brain AD pathology before any symptomatic evidence of cognitive impairment. Identifying such high-risk groups might allow tailored interventions for AD prevention.

Chemopreventive Effects of Polysaccharides and Flavonoids from Okra Flowers in Azomethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer.

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.

Large effective magnetic fields from chiral phonons in rare-earth halides.

Time-reversal symmetry (TRS) is pivotal for materials' optical, magnetic, topological, and transport properties. Chiral phonons, characterized by atoms rotating unidirectionally around their equilibrium positions, generate dynamic lattice structures that break TRS. Here, we report that coherent chiral phonons, driven by circularly polarized terahertz light pulses, polarize the paramagnetic spins in cerium fluoride in a manner similar to that of a quasi-static magnetic field on the order of 1 tesla. Through time-resolved Faraday rotation and Kerr ellipticity, we found that the transient magnetization is only excited by pulses resonant with phonons, proportional to the angular momentum of the phonons, and growing with magnetic susceptibility at cryogenic temperatures. The observation quantitatively agrees with our spin-phonon coupling model and may enable new routes to investigating ultrafast magnetism, energy-efficient spintronics, and nonequilibrium phases of matter with broken TRS.

Does endometrial compaction before embryo transfer affect pregnancy outcomes? a systematic review and meta-analysis.

Objective: There is no clear evidence of clinical significance of endometrial compaction, which can be measured by a reduction in endometrial thickness (EMT) during the follicular-luteal transition before the day of embryo transfer. In this study, we aim to determine whether endometrial compaction has an effect on in vitro fertilization (IVF) success. Methods: We searched PubMed, Cochrane, Embase, and Web of Science electronic databases for studies published in English up to March 2023. Heterogeneity between studies was assessed using the I2 statistic. The random effects model and fixed effects model was used to pool the risk ratio (RR) with a corresponding 95% confidence interval (CI). A subgroup analysis was performed based on different methods of ultrasonic measurement and different endometrial compaction rates (ECR). Stata 17.0 software was used for meta-analysis. Pregnancy outcomes, which included clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and spontaneous abortion rate, were evaluated. Results: In this study, 18 cohort studies were included, involving 16,164 embryo transfer cycles. Pooled results indicated that there was no significant difference between the endometrial compaction group and the non-compaction group in terms of clinical pregnancy rate (RR [95% CI]=0.98 [0.90,1.08]; I2 = 69.76%), ongoing pregnancy rate (RR [95% CI]=1.18 [0.95,1.47]; I2 = 78.77%), live birth rate (RR [95% CI]= 0.97 [0.92,1.02]; I2 = 0.00%) or spontaneous abortion rate (RR [95% CI]= 1.07[0.97,1.26]; I2 = 0.00%). According to the subgroup analysis of ultrasonic measurement methods, in the transvaginal ultrasound (TVUS) combined with abdominal ultrasonography (AUS) cycles of the endometrial compaction group, the rate of ongoing pregnancy (RR [95% CI] = 1.69 [1.26, 2.26]; I2 = 29.27%) and live birth (RR [95% CI] = 1.27 [1.00,1.61]; I2 = 62.28%) was significantly higher than that of the non-compaction group. Additionally, subgroup analysis based on ECR revealed a significantly higher rate of ongoing pregnancy when ECR ≥ 15% (RR [95% CI] = 1.99 [1.61, 2.47]; I2 = 0.00%). Conclusion: Endometrial compaction has no adverse effect on clinical pregnancy rate, ongoing pregnancy rate, live birth rate, or spontaneous abortion rate. A possible explanation for the contradictory findings of previous studies lies in the method by which the EMT is measured. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430511, identifier CRD42023430511.

Development and performance validation of a low-cost algorithms-based hyperspectral imaging system for radiodermatitis assessment.

Whilst radiotherapy (RT) is widely used for cancer treatment, radiodermatitis caused by RT is one most common severe side effect affecting 95% cancer patients. Accurate radiodermatitis assessment and classification is essential to adopt timely treatment, management and monitoring, which all depend on reliable and objective tools for radiodermatitis grading. We therefore, in this work, reported the development and grading performance validation of a low-cost (∼2318.2 CNY) algorithms-based hyperspectral imaging (aHSI) system for radiodermatitis assessment. The low-cost aHSI system was enabled through Monte Carlo (MC) simulations conducted on multi-spectra acquired from a custom built low-cost multispectral imaging (MSI) system, deriving algorithms-based hyper-spectra with spectral resolution of 1 nm. The MSI system was based on sequentially illuminated narrow-band light-emitting diodes (LEDs) and a CMOS camera. Erythema induced artificially on healthy volunteers was measured by the aHSI system developed, with algorithms-based hyper-spectra and skin layer resolved physiological parameters (i.e., the blood volume fraction (BVF) and the oxygen saturation of hemoglobin in blood, et. al.) derivation using MC simulations. The MC simulations derived BVF and the oxygen saturation of hemoglobin in blood showed significant (P < 0.001, analysis of variance: ANOVA) increase with erythema. Further 1D-convolution neural network (CNN) implemented on the algorithms-based hyper-spectra leads to an overall classification accuracy of 93.1%, suggesting the great potential of low-cost aHSI system developed for radiodermatitis assessment.

Biotin-decorated hollow gold nanoshells for dual-modal imaging-guided NIR-II photothermal and radiosensitizing therapy toward breast cancer.

Radiotherapy (RT) is dominantly used in breast cancer therapy but is facing fierce side effects because of the limited difference between tumor and normal tissues in response to ionizing radiation. Herein, we construct a core-shell nanoparticle of UiO-66-NH2@AuNS. Then the solid gold shell was etched into hollow AuNS (HAuNS) and further modified with biotin-PEG-SH (PEG-bio) to obtain HAuNS@PEG-bio. HAuNS@PEG-bio demonstrates effective near infrared II (NIR-II) region photothermal therapy (PTT) performance, and the increase of temperature at the tumor site promotes the blood circulation to alleviate the hypoxia in the tumor microenvironment (TME). Meanwhile, HAuNS exhibits strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au (Z = 79) and hollowed-out structure. Through the dual radiosensitization of the high atomic coefficient of Au and the hypoxia alleviation from PTT of HAuNS, the breast cancer cells could undergo immunogenic cell death (ICD) to activate the immune response. At the in vivo level, HAuNS@PEG-bio performs NIR-II photothermal, radiosensitization, and ICD therapies through cellular targeting, guided by infrared heat and CT imaging. This work highlights that the constructed biotin-decorated hollow gold nanoshell has a promising potential as a diagnostic and treatment integration reagents for the breast cancer.

Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis (p-value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4+ T cell, CD8+ T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8+ T cells, resting memory CD4+ T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.