Transcriptomics analysis of LINC02202/XBP1 axis in melanoma: Implications for drug targeting and PD-1 monoclonal antibody efficacy.

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.

Ligand-Bound CO2 as a Nonclassical Route toward Efficient Photocatalytic CO2 Reduction with a Ni N-Confused Porphyrin.

Implementing the synergistic effects between the metal and the ligand has successfully streamlined the energetics for CO2 activation and gained high catalytic activities, establishing the important breakthroughs in photocatalytic CO2 reduction. Herein, we describe a Ni(II) N-confused porphyrin complex (NiNCP) featuring an acidic N-H group. It is readily deprotonated and exists in an anion form during catalysis. Owing to this functional site, NiNCP gave rise to an outstanding turnover number (TON) as high as 217,000 with a 98% selectivity for CO2 reduction to CO, while the parent Ni(II) porphyrin (NiTPP) was found to be nearly inactive. Our mechanistic analysis revealed a nonclassical reaction pattern where CO2 was effectively activated via the attack of the Lewis-basic ligand. The resulting ligand-bound CO2 adduct could be further reduced to produce CO. This new metal-ligand synergistic effect is anticipated to inspire the design of highly active catalysts for small molecule activations.

Single-cell sequencing of tumour infiltrating T cells efficiently identifies tumour-specific T cell receptors based on the T cell activation score.

Adoptively transferred T cell receptor-engineered T cells are a promising cancer treatment strategy, and the identification of tumour-specific TCRs is essential. Previous studies reported that tumour-reactive T cells and TCRs could be isolated based on the expression of activation markers. However, since T cells with different cell states could not respond uniformly to activation but show a heterogeneous expression profile of activation and effector molecules, isolation of tumour-reactive T cells based on single activation or effector molecules could result in the absence of tumour-reactive T cells; thus, combinations of multiple activation and effector molecules could improve the efficiency of isolating tumour-specific TCRs. We enrolled two patients with lung adenocarcinoma and obtained their tumour infiltrating lymphocytes (TILs) and autologous tumour cells (ATCs). TILs were cocultured with the corresponding ATCs for 12 h and subjected to single-cell RNA sequencing. First, we identified three TCRs with the highest expression levels of IFNG and TNFRSF9 mRNA for each patient, yet only the top one or two recognized the corresponding ATCs in each patient. Next, we defined the activation score based on normalized expression levels of IFNG, IL2, TNF, IL2RA, CD69, TNFRSF9, GZMB, GZMA, GZMK, and PRF1 mRNA for each T cell and then identified three TCRs with the highest activation score for each patient. We found that all three TCRs in each patient could specifically identify corresponding ATCs. In conclusion, we established an efficient approach to isolate tumour-reactive TCRs based on combinations of multiple activation and effector molecules through single-cell RNA sequencing.

Accelerating Charge Kinetics in Photocatalytic CO2 Reduction by Modulating the Cobalt Coordination in Heterostructures of Cadmium Sulfide/Metal-Organic Layer.

Artificial photocatalytic CO2 reduction (CO2R) holds great promise to directly store solar energy into chemical bonds. The slow charge and mass transfer kinetics at the triphasic solid-liquid-gas interface calls for the rational design of heterogeneous photocatalysts concertedly boosting interfacial charge transfer, local CO2 concentration, and exposure of active sites. To meet these requirements, in this study heterostructures of CdS/MOL (MOL = metal-organic layer) furnishing different redox Co sites are fabricated for CO2R photocatalysts. It is found that the coordination environment of Co is key to photocatalytic activity. The best catalyst ensemble comprising ligand-chelated Co2+ with the bipyridine electron mediator demonstrates a high CO yield rate of 1523 µmol h-1 gcat -1, selectivity of 95.8% and TON of 1462.4, which are ranked among the best seen in literature. Comprehensive photochemical and electroanalytical characterizations attribute the high CO2R performance to the improved photocarrier separation and charge kinetics originated from the proper energy band alignment and coordination chemistry. This work highlights the construction of 2D heterostructures and modulation of transition metal coordination to expedite the charge kinetics in photocatalytic CO2 reduction.

Identifying a survival-associated cell type based on multi-level transcriptome analysis in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a five-year survival rate of less than 40%. There is significant variability in survival time among IPF patients, but the underlying mechanisms for this are not clear yet. METHODS AND RESULTS: We collected single-cell RNA sequence data of 13,223 epithelial cells taken from 32 IPF patients and bulk RNA sequence data from 456 IPF patients in GEO. Based on unsupervised clustering analysis at the single-cell level and deconvolution algorithm at bulk RNA sequence data, we discovered a special alveolar type 2 cell subtype characterized by high expression of CCL20 (referred to as ATII-CCL20), and found that IPF patients with a higher proportion of ATII-CCL20 had worse prognoses. Furthermore, we uncovered the upregulation of immune cell infiltration and metabolic functions in IPF patients with a higher proportion of ATII-CCL20. Finally, the comprehensive decision tree and nomogram were constructed to optimize the risk stratification of IPF patients and provide a reference for accurate prognosis evaluation. CONCLUSIONS: Our study by integrating single-cell and bulk RNA sequence data from IPF patients identified a special subtype of ATII cells, ATII-CCL20, which was found to be a risk cell subtype associated with poor prognosis in IPF patients. More importantly, the ATII-CCL20 cell subtype was linked with metabolic functions and immune infiltration.

Magnetic resonance imaging features of progressive familial intrahepatic cholestasis type 3.

PURPOSE: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder. This study aimed to present the clinical and magnetic resonance imaging (MRI) features of three patients with PFIC­3. METHODS: The study included three patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing of a targeted-gene panel or by whole-exome sequencing. The clinical, laboratory, histological, molecular, and MRI features of the patients were collected. RESULTS: Three patients (one male and two females) were enrolled. The age when clinical signs and symptoms were first noted was 21, 14, and 39 years, respectively, and the signs and symptoms included pruritus and splenomegaly (in all three patients). Parenchymatous lace-like fibrosis was associated with periportal hyperintensity and periportal halo sign in three patients. Segmental atrophy was observed in two patients, diffuse atrophy was observed in one patient, and liver surface irregularity caused by regenerating nodules was observed in three patients. Magnetic resonance cholangiopancreatography (MRCP) images showed irregular bile duct changes in three patients, focal hilar bile duct stenosis, and local intrahepatic bile duct dilatation. CONCLUSIONS: Imaging studies using MRI and MRCP can support the clinical and laboratory results in cases of PFIC­3 and can also be used as a noninvasive diagnostic option.

Distribution and community structure of antibiotic resistance genes in the Three Gorges Reservoir Area.

Antibiotic resistance genes (ARG) are widespread across various regions. While several studies have investigated the distribution of antibiotic resistance in natural environments, the occurrence and diversity of ARGs in the Three Gorges Reservoir have not been fully elucidated. In this study, we employed metagenomic sequencing techniques to investigate the abundance, diversity, and influencing factors of ARGs in the ecosystem of the Three Gorges Reservoir. A total of 874 ARGs, 20 antibiotic classes, and 6 resistance mechanisms were detected. The dominant ARG is the macB, the dominant antibiotic class is multidrug resistance (MDR), and the dominant resistance mechanism is antibiotic efflux. The microorganisms with the highest contribution to ARGs are Betaproteobacteria and Gammaproteobacteria. In this region, pH and NH4+ concentration were significantly negatively correlated with the relative abundance of most ARGs, while NO3- concentration and TN were significantly positively correlated with the relative abundance of most ARGs. The results indicate that the Three Gorges Reservoir constitutes a significant reservoir of ARGs. By studying the distribution of ARGs in the sediments of the Three Gorges Reservoir Area and the relationship between environmental factors and ARGs, we can more comprehensively understand the pollution status of ARGs in this area, and provide theoretical support for subsequent treatment.

Nomograms based on multiparametric MRI radiomics integrated with clinical-radiological features for predicting the response to induction chemotherapy in nasopharyngeal carcinoma.

OBJECTIVE: To establish nomograms integrating multiparametric MRI radiomics with clinical-radiological features to identify the responders and non-responders to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). METHODS: We retrospectively analyzed the clinical and MRI data of 168 NPC patients between December 2015 and April 2022. We used 3D-Slicer to segment the regions of interest (ROIs) and the "Pyradiomic" package to extract radiomics features. We applied the least absolute shrinkage and selection operator regression to select radiomics features. We developed clinical-only, radiomics-only, and the combined clinical-radiomics nomograms using logistic regression analysis. The receiver operating characteristic curves, DeLong test, calibration, and decision curves were used to assess the discriminative performance of the models. The model was internally validated using 10-fold cross-validation. RESULTS: A total of 14 optimal features were finally selected to develop a radiomic signature, with an AUC of 0.891 (95 % CI, 0.825-0.946) in the training cohort and 0.837 (95 % CI, 0.723-0.932) in the testing cohort. The nomogram based on the Rad-Score and clinical-radiological factors for evaluating tumor response to ICT yielded an AUC of 0.926 (95 % CI, 0.875-0.965) and 0.901 (95 % CI, 0.815-0.979) in the two cohorts, respectively. Decision curves demonstrated that the combined clinical-radiomics nomograms were clinically useful. CONCLUSION: Nomograms integrating multiparametric MRI-based radiomics and clinical-radiological features could non-invasively discriminate ICT responders from non-responders in NPC patients.

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis.

Background: The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods: This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients' responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results: The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion: Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Derived Neutrophils to Lymphocyte Ratio Predicts Survival Benefit from TPF Induction Chemotherapy in Local Advanced Oral Squamous Cellular Carcinoma.

BACKGROUND: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). METHODS: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan-Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. RESULTS: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018-1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000-1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002-1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010-1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. CONCLUSIONS: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC.

Efficient near-infrared emission benefits from slowing down the internal conversion process.

Organic deep-red (DR) and near-infrared (NIR) emitters with high photoluminescence quantum yield (PLQY) are rare due to the strong non-radiative (knr) decay. Here, we report two DR/NIR emitters with high PLQY, TPANZPyPI and TPANZ3PI. Interestingly, the TPANZPyPI film exhibits 46.5% PLQY at 699 nm. Theoretical calculations indicate that TPANZPyPI can achieve this high PLQY in the near-infrared emission region due to its small S1 to S0 internal conversion (IC) rate. Meanwhile, research has found that, compared to TPANZ3PI, TPANZPyPI with a more rigid structure can effectively suppress the T2 to T1 IC process, which is conducive to higher exciton utilization efficiency (EUE). TPANZPyPI's non-doped OLED shows NIR emission with 4.6% @ 684 nm maximum external quantum efficiency (EQEmax). Its doped OLEDs radiate DR with an EQEmax of 6.9% @ 666 nm. These EQEs are among the highest values for hybridized local charge transfer state materials emitting more than 640 nm. This work demonstrates for the first time, based on a combination of theory and experiment, that increasing the molecular rigidity can inhibit the excited state IC process in addition to the S1 to S0 IC, realizing efficient electroluminescence.

The morphological discrepancy of neuromuscular junctions between bilateral paraspinal muscles in patients with adolescent idiopathic scoliosis: A quantitative immunofluorescence assay.

Introduction: Prior studies suggested that neuromuscular factors might be involved in the pathogenesis of adolescent idiopathic scoliosis (AIS). The neuromuscular junction (NMJ) is the important pivot where the nervous system interacts with muscle fibers, but it has not been well characterized in the paraspinal muscles of AIS. This study aims to perform the quantitative morphological analysis of NMJs from paraspinal muscles of AIS. Methods: AIS patients who received surgery in our center were prospectively enrolled. Meanwhile, age-matched congenital scoliosis (CS) and non-scoliosis patients were also included as controls. Fresh samples of paraspinal muscles were harvested intraoperatively. NMJs were immunolabeled using different antibodies to reveal pre-synaptic neuronal architecture and post-synaptic motor endplates. A confocal microscope was used to acquire z-stack projections of NMJs images. Then, NMJs images were analyzed on maximum intensity projections using ImageJ software. The morphology of NMJs was quantitatively measured by a standardized 'NMJ-morph' workflow. A total of 21 variables were measured and compared between different groups. Results: A total of 15 AIS patients, 10 CS patients and 5 normal controls were enrolled initially. For AIS group, NMJs in the convex side of paraspinal muscles demonstrated obviously decreased overlap when compared with the concave side (34.27% ± 8.09% vs. 48.11% ± 10.31%, p = 0.0036). However, no variables showed statistical difference between both sides of paraspinal muscles in CS patients. In contrast with non-scoliosis controls, both sides of paraspinal muscles in AIS patients demonstrated significantly smaller muscle bundle diameters. Conclusions: This study first elucidated the morphological features of NMJs from paraspinal muscles of AIS patients. The NMJs in the convex side showed smaller overlap for AIS patients, but no difference was found in CS. This proved further evidence that neuromuscular factors might contribute to the mechanisms of AIS and could be considered as a novel potential therapeutic target for the treatment of progressive AIS.

Improving electron transportation and operational lifetime of full color organic light emitting diodes through a "weak hydrogen bonding cage" structure.

Efficient electron-transporting materials (ETMs) are critical to achieving excellent performance of organic light-emitting diodes (OLEDs), yet developing such materials remains a major long-term challenge, particularly ETMs with high electron mobilities (µeles). Herein, we report a short conjugated ETM molecule (PICN) with a dipolar phenanthroimidazole group, which exhibits an electron mobility of up to 1.52 × 10-4 cm2 (V-1 s-1). The origin of this high µele is long-ranged, regulated special cage-like interactions with C-H⋯N radii, which are also favorable for the excellent efficiency stability and operational stability in OLEDs. It is worth noting that the green phosphorescent OLED operation half-lifetimes can reach up to 630 h under unencapsulation, which is 20 times longer than that based on the commonly used commercial ETM TPBi.

Changing effects of energy and water on the richness distribution pattern of the Quercus genus in China.

Climate varies along geographic gradients, causing spatial variations in the effects of energy and water on species richness and the explanatory power of different climatic factors. Species of the Quercus genus are important tree species in China with high ecological and socioeconomic value. To detect whether the effects of energy and water on species richness change along climatic gradients, this study built geographically weighted regression models based on species richness and climatic data. Variation partition analysis and hierarchical partitioning analysis were used to further explore the main climatic factors shaping the richness distribution pattern of Quercus in China. The results showed that Quercus species were mainly distributed in mountainous areas of southwestern China. Both energy and water were associated with species richness, with global slopes of 0.17 and 0.14, respectively. The effects of energy and water on species richness gradually increased as energy and water in the environment decreased. The interaction between energy and water altered the effect of energy, and in arid regions, the effects of energy and water were relatively stronger. Moreover, energy explained more variation in species richness in both the entire study area (11.5%) and different climate regions (up to 19.4%). The min temperature of coldest month was the main climatic variable forming the richness distribution pattern of Quercus in China. In conclusion, cold and drought are the critical climatic factors limiting the species richness of Quercus, and climate warming will have a greater impact in arid regions. These findings are important for understanding the biogeographic characteristics of Quercus and conserving biodiversity in China.

Dietary Bacillus velezensis KNF-209 supplementation improves growth performance, enhances immunity, and promotes gut health in broilers.

This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1ß and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1ß and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels.

Effects of the pesticide carbendazim on broiler chicken health and carbendazim residue levels in broiler tissues.

Pesticide residues may enter the human body through the food chain when livestock and poultry consume pesticide-contaminated feed. Therefore, monitoring and limiting pesticide residues in animal feed and animal-origin foods is necessary. Carbendazim is one of the most frequently detected pesticides in food and feed and has various toxic effects on non-target animals. This study investigated the effects of varying concentrations of carbendazim contamination in feed on broiler chicken growth performance, serum biochemical indicators, histopathology, and carbendazim residues in broiler muscles and livers. The results demonstrated that contamination of 5-100 mg/kg carbendazim in feed did not affect broiler growth performance or health. Carbendazim contamination in feed at 200-800 mg/kg slightly reduced growth performance. Broiler kidneys showed minor histopathological alterations after 400 mg/kg carbendazim exposure. Furthermore, when the carbendazim content in feed was less than 25 mg/kg, the residual carbendazim in the muscles and livers of broilers did not exceed the maximum residue level set by the European Union and China. Based on the above findings, carbendazim residues in the feed of less than 25 mg/kg can be considered safe for chicken products.

Biogenic manganese oxides promote metal(loid) remediation by shaping microbial communities in biological aqua crust.

Biological aqua crust (biogenic aqua crust-BAC) is a potentially sustainable solution for metal(loid) bioremediation in global water using solar energy. However, the key geochemical factors and underlying mechanisms shaping microbial communities in BAC remain poorly understood. The current study aimed at determining the in situ metal(loid) distribution and the key geochemical factors related to microbial community structure and metal(loid)-related genes in BAC of a representative Pb/Zn tailing pond. Here we showed that abundant metal(loid)s (e.g. Pb, As) were co-distributed with Mn/Fe-rich minerals (e.g. biogenic Mn oxide, FeOOH) in BAC. Biogenic Mn oxide (i.e. Mn) was the most dominant factor in shaping microbial community structure in BAC and source tailings. Along with the fact that keystone species (e.g. Burkholderiales, Haliscomenobacter) have the potential to promote Mn ion oxidization and particle agglomeration, as well as Mn is highly associated with metal(loid)-related genes, especially genes related to As redox (e.g. arsC, aoxA), and Cd transport (e.g. zipB), biogenic Mn oxides thus effectively enhance metal(loid) remediation by accelerating the formation of organo-mineral aggregates in biofilm-rich BAC system. Our study indicated that biogenic Mn oxides may play essential roles in facilitating in situ metal(loid) bioremediation in BAC of mine drainage.

MRI Manifestations of Breast Cancer Stroma and their Role in Predicting Molecular Subtype: A Case-control Study.

OBJECTIVE: This study explored whether breast MRI manifestations could be used to predict the stroma distribution of breast cancer (BC) and the role of tumor stroma-based MRI manifestations in molecular subtype prediction. METHODS: 57 patients with pathologically confirmed invasive BC (non-special type) who had lumpy BC on MRI within one week before surgery were retrospectively collected in the study. Stroma distributions were classified according to their characteristics in the pathological sections. The stromal distribution patterns among molecular subtypes were compared with the MRI manifestations of BC with different stroma distribution types (SDTs). RESULTS: SDTs were significantly different and depended on the BC hormone receptor (HR) (P<0.001). There were also significant differences among five SDTs on T2WI, ADC map, internal delayed enhanced features (IDEF), marginal delayed enhanced features (MDEF), and time signal intensity (TSI) curves. Spiculated margin and the absence of type-I TSI were independent predictors for BC with star grid type stroma. The appearance frequency of hypo-intensity on T2WI in HR- BCs was significantly lower (P=0.043) than in HR+ BCs. Star grid stroma and spiculated margin were key factors in predicting HR+ BCs, and the AUC was 0.927 (95% CI: 0.867-0.987). CONCLUSION: Breast MRI can be used to predict BC's stromal distribution and molecular subtypes.

Genetic Engineering Bacillus thuringiensis Enable Melanin Biosynthesis for Anti-Tumor and Anti-Inflammation.

Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin-producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco-friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal-conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS-scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.

Gut microbial features and circulating metabolomic signatures of frailty in older adults.

Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62-96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic data. We identified 18 microbial species and 17 metabolites shifted along with frailty severity, with stronger links observed in females. The associations of nine species, including various Clostridium species and Faecalibacterium prausnitzii, with FI were reproducible in two external populations. Plasma glycerol levels, white blood cell count and kidney function partially mediated these associations. A composite microbial score derived from FI significantly predicted 2-year mortality (adjusted hazard ratio across extreme quartiles, 2.86; 95% confidence interval, 1.38-5.93), highlighting the potential of microbiota-based strategies for risk stratification in older adults.