Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation.

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

Preparation of VC nanoliposomes by high pressure homogenization: Process optimization and evaluation of efficacy, transdermal absorption, and stability.

Vitamin C (VC) possesses antioxidant and whitening effects. However, its effectiveness is hindered by challenges such as instability, impaired solubility, and limited bioavailability hinder. In this study, VC was encapsulated in nanoliposomes by primary emulsification and high-pressure homogenization. The VC nanoliposomes were comprehensively characterized for their microscopic morphology, particle size, polydispersity index (PDI), and encapsulation efficiency (EE). Orthogonal experiments were designed to optimize the optimal preparation process, and the antioxidant activity, whitening efficacy, transdermal absorption, and stability of VC nanoliposomes were evaluated based on this optimized process. The findings demonstrated the high reproducibility of the optimal process, with particle size, PDI, and EE values of 113.502 ± 4.360 nm, 0.104 ± 0.010, and 56.09 ± 1.01 %, respectively. Differential scanning calorimetry analysis showed effective encapsulation of VC nanoliposomes with better thermal stability than aqueous VC solution. Besides, the VC nanoliposomes demonstrated excellent antioxidant and whitening effects in efficacy experiments, stronger skin permeability in transdermal experiments and fluorescence tracking. Furthermore, storage stability tests indicated that the VC in nanoliposomes remained relatively stable after 60 days of storage. These findings highlighted the potential use of VC nanoliposomes in a wide range of applications for the cosmetic market, especially in the development of ingredients for skin care products.

Per- and polyfluoroalkyl substances (PFAS) exposure in plasma and their blood-brain barrier transmission efficiency-A pilot study.

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.

Utility of a modified o-DGT passive sampler for measurement of bisphenol analogues in freshwater and coastal waters.

Bisphenol analogues (BPs) are commonly found in riverine and coastal waters. However, the lack of a reliable and robust passive sampling method has hindered our ability to monitor these compounds in aquatic systems. The study developed a novel organic-diffusive gradients in thin film (o-DGT) sampler based on stainless steel mesh membrane, polyacrylamide diffusive gel, and hydrophilic-lipophilic balance (HLB) binding gel. This innovative design tackled issues of filter membrane sorption in traditional o-DGT devices and potential gel damage in membrane-less o-DGT devices, showing promising application prospects. The mass accumulation of 15 target BPs was linear over 10 days in both freshwater (r2 ≥ 0.92) and seawater (r2 ≥ 0.94), with no saturation observed. The diffusion coefficients (D) through polyacrylamide diffusive gels ranged from 4.04 × 10-6 to 5.77 × 10-6 cm2 s-1 in freshwater and from 1.74 × 10-6 to 4.69 × 10-6 cm2 s-1 in seawater for the target BPs (except for bisphenol PH) at 22 °C. The D values of the target BPs in seawater were lower than those in freshwater due to the high salinity in seawater (35 ‰). The o-DGT samplers demonstrated good integrity in field applications. The total concentrations of the eight detected BPs ranged from 9.2 to 323 ng L-1, which was consistent with the measurements obtained by grab sampling. Among all BPs, bisphenol S, bisphenol F, and bisphenol A were consistently detected at all sites using both sampling methods. The concentrations of some novel BPs in coastal water measured by grab sampling were comparable to those measured in rivers, suggesting the need to strengthen pollution control of BPs in coastal areas. These results indicate that the o-DGT passive sampling method developed in the present study can be effectively used for monitoring BPs in freshwater and coastal environments.

Application of Genetic Information to Cochlear Implantation in Clinical Practice.

Cochlear implantation is currently the treatment of choice for children with severe-to-profound sensorineural hearing impairment (SNHI). However, the outcomes with cochlear implant (CI) vary significantly among recipients. Genetic diagnosis offers direct clues regarding the pathogenesis of SNHI, which facilitates the development of personalized medicine for potential candidates for CI. In this article, I present a comprehensive overview of the usefulness of genetic information in clinical decision-making for CI. Genetically confirmed diagnosis enables clinicians to: 1) monitor the evolution of SNHI and determine the optimal surgical timing, 2) predict the potential benefits of CI in patients with identified genetic etiology, and 3) select CI devices/electrodes tailored to patients with specific genetic mutations.

The coupling of sulfide and Fe-Mn mineral promotes the migration of lead and zinc in the redox cycle of high pH floodplain soils.

In this study, we investigated the impact of fluctuating water levels on the distribution of lead (Pb) and zinc (Zn) in soil and sediments at a historical Pb-Zn smelting site along the Xiangjiang River. Despite the high pH levels (7 to 11) in the study area, which generally inhibits heavy metal solubility, we found that regular changes in water levels still affect Pb-Zn movement. Soil analysis revealed distinct redox zones within the unconfined aquifer, as shown by the variable Fe/Mn and Ce/Ce* ratios. Advanced techniques such as Mn K-edge XAFS, Mössbauer spectroscopy, and TOF-SIMS indicated persistent Fe-Mn redox cycling and highlighted the presence of Pb and Zn-rich manganese oxides near sulfur-bearing minerals. These findings suggest that acidic microzones produced by the oxidation of sulfur-bearing minerals become "refuges" for microbial and heavy metal activity. Considering that sulfur-containing minerals are widespread waste types in nonferrous metal smelting sites, these findings are instructive for a better understanding of the transformation mechanisms of heavy metal ions in nonferrous metal smelting-polluted environments and for guiding pollution remediation strategies.

Research on Hydrogen-Induced Induced Cracking Sensitivity of X80 Pipeline Steel under Different Heat Treatments.

X80 pipeline steel has played a vital role in oil and gas transportation in recent years. However, hydrogen-related issues frequently lead to pipeline failures during service, resulting in significant losses of properties and lives. Three heat treatment processes (furnace cooling (FC), air cooling (AC), and water cooling (WC)) were carried out to investigate the effect of different microstructures on hydrogen-induced cracking (HIC) susceptibility of X80 pipeline steel. The WC sample demonstrated the highest hydrogen embrittlement index, registering at 21.9%, while the AC and FC samples exhibited progressively lower values of 15.45% and 10.98%, respectively. Under equivalent hydrogen charging durations, crack dimensions with a maximum length exceeding 30 µm in the WC sample generally exceed those in the FC sample and AC sample. The variation is attributed to the difference in microstructures of the samples, predominantly lath bainite (LB) in water-cooled samples, granular bainite (GB) in air-cooled samples, and ferrite/pearlite (F/P) in FC samples. The research results demonstrate that the sensitivity of lath bainite (LB) to HIC is significantly higher than that of pearlite, ferrite, and granular bainite (GB). The presence of a large amount of martensite/austenite (M/A) constituents within bainite results in a multitude of hydrogen trap sites. HIC cracks in bainite generally propagate along the profiles of M/A constituents, showing both intergranular and transgranular cracking modes.

Enhancing Mechanical and Antimicrobial Properties of Dialdehyde Cellulose-Silver Nanoparticle Composites through Ammoniated Nanocellulose Modification.

Given the widespread prevalence of viruses, there is an escalating demand for antimicrobial composites. Although the composite of dialdehyde cellulose and silver nanoparticles (DAC@Ag1) exhibits excellent antibacterial properties, its weak mechanical characteristics hinder its practical applicability. To address this limitation, cellulose nanofibers (CNFs) were initially ammoniated to yield N-CNF, which was subsequently incorporated into DAC@Ag1 as an enhancer, forming DAC@Ag1/N-CNF. We systematically investigated the optimal amount of N-CNF and characterized the DAC@Ag1/N-CNF using FT-IR, XPS, and XRD analyses to evaluate its additional properties. Notably, the optimal mass ratio of N-CNF to DAC@Ag1 was found to be 5:5, resulting in a substantial enhancement in mechanical properties, with a 139.8% increase in tensile elongation and a 33.1% increase in strength, reaching 10% and 125.24 MPa, respectively, compared to DAC@Ag1 alone. Furthermore, the inhibition zones against Escherichia coli and Staphylococcus aureus were significantly expanded to 7.9 mm and 15.9 mm, respectively, surpassing those of DAC@Ag1 alone by 154.8% and 467.9%, indicating remarkable improvements in antimicrobial efficacy. Mechanism analysis highlighted synergistic effects from chemical covalent bonding and hydrogen bonding in the DAC@Ag1/N-CNF, enhancing the mechanical and antimicrobial properties significantly. The addition of N-CNF markedly augmented the properties of the composite film, thereby facilitating its broader application in the antimicrobial field.

Extracellular vesicles derived from immune cells: Role in tumor therapy.

Extracellular vesicles (EVs), which have a lipid nano-sized structure, are known to contain the active components of parental cells and play a crucial role in intercellular communication. The progression and metastasis of tumors are influenced by EVs derived from immune cells, which can simultaneously stimulate and suppress immune responses. In the past few decades, there has been a considerable focus on EVs due to their potential in various areas such as the development of vaccines, delivering drugs, making engineered modifications, and serving as biomarkers for diagnosis and prognosis. This review focuses on the substance information present in EVs derived from innate and adaptive immune cells, their effects on the immune system, and their applications in cancer treatment. While there are still challenges to overcome, it is important to explore the composition of immune cells released vesicles and their potential therapeutic role in tumor therapy. The review also highlights the current limitations and future prospects in utilizing EVs for treatment purposes.

Development of a simulation system for femoroacetabular impingement detection based on 3D images.

Image-based criteria have been adopted to diagnose femoroacetabular impingement (FAI). However, the overlapping property of the two-dimensional X-ray outlines and static and supine posture of taking computed tomography (CT) and magnetic resonance imaging images potentially affect the accuracy of the criteria. This study developed a CT image-based dynamic criterion to effectively simulate FAI, thereby providing a basis for physicians to perform pre-operative planning for arthroscopic surgery. Post-operative CT images of 20 patients with satisfactory surgical results were collected, and 10 sets of models were used to define the flexion rotation centre (FRC) of the three-dimensional FAI model. First, let these 10 groups of models simulate the FAI detection action and find the best centre offset, and then FRC is the result of averaging these 10 groups of best displacements. The model was validated in 10 additional patients. Finally, through the adjustment basis of FRC, the remaining 10 sets of models can find out the potential position of FAI during the dynamic simulation process. Rotational collisions detected using FRC indicate that the patient's post-operative flexion angle may reach 120° or greater, which is close to the actual result. The recommended surgical range of the diagnostic system (average length of 6.4 mm, width of 4.1 mm and depth of 3.2 mm) is smaller than the actual surgical results, which prevents the doctor from performing excessive resection operations, which may preserve more bones. The FRC diagnostic system detects the distribution of FAI in a simple manner. It can be used as a pre-operative diagnosis reference for clinicians, hoping to improve the effect and accuracy of debridement surgery.

Treatment patterns and survival outcomes in patients with non-metastatic early-onset pancreatic cancer.

BACKGROUND: The incidence of patients with early-onset pancreatic cancer (EOPC; age ≤ 50 years at diagnosis) is on the rise, placing a heavy burden on individuals, families, and society. The role of combination therapy including surgery, radiotherapy, and chemotherapy in non-metastatic EOPC is not well-defined. AIM: To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC. METHODS: A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively. Overall survival (OS), disease-free survival, and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors. RESULTS: With a median follow-up time of 34.6 months, the 1-year, 2-year, and 3-year OS rates for the entire cohort were 84.3%, 51.5%, and 27.6%, respectively. The median OS of patients with localized disease who received surgery alone and adjuvant therapy (AT) were 21.2 months and 28.8 months, respectively (P = 0.007). The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy (RCT), surgery after neoadjuvant therapy (NAT), and chemotherapy were 28.5 months, 25.6 months, and 14.0 months, respectively (P = 0.002). The median OS after regional recurrence were 16.0 months, 13.4 months, and 8.9 months in the RCT, chemotherapy, and supportive therapy groups, respectively (P = 0.035). Multivariate analysis demonstrated that carbohydrate antigen 19-9 level, pathological grade, T-stage, N-stage, and resection were independent prognostic factors for non-metastatic EOPC. CONCLUSION: AT improves postoperative survival in localized patients. Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Beneficial impact of visual stimulation-based digital therapeutics on blood pressure control in non-hypertensive individuals.

Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.

Large language models facilitate the generation of electronic health record phenotyping algorithms.

OBJECTIVES: Phenotyping is a core task in observational health research utilizing electronic health records (EHRs). Developing an accurate algorithm demands substantial input from domain experts, involving extensive literature review and evidence synthesis. This burdensome process limits scalability and delays knowledge discovery. We investigate the potential for leveraging large language models (LLMs) to enhance the efficiency of EHR phenotyping by generating high-quality algorithm drafts. MATERIALS AND METHODS: We prompted four LLMs-GPT-4 and GPT-3.5 of ChatGPT, Claude 2, and Bard-in October 2023, asking them to generate executable phenotyping algorithms in the form of SQL queries adhering to a common data model (CDM) for three phenotypes (ie, type 2 diabetes mellitus, dementia, and hypothyroidism). Three phenotyping experts evaluated the returned algorithms across several critical metrics. We further implemented the top-rated algorithms and compared them against clinician-validated phenotyping algorithms from the Electronic Medical Records and Genomics (eMERGE) network. RESULTS: GPT-4 and GPT-3.5 exhibited significantly higher overall expert evaluation scores in instruction following, algorithmic logic, and SQL executability, when compared to Claude 2 and Bard. Although GPT-4 and GPT-3.5 effectively identified relevant clinical concepts, they exhibited immature capability in organizing phenotyping criteria with the proper logic, leading to phenotyping algorithms that were either excessively restrictive (with low recall) or overly broad (with low positive predictive values). CONCLUSION: GPT versions 3.5 and 4 are capable of drafting phenotyping algorithms by identifying relevant clinical criteria aligned with a CDM. However, expertise in informatics and clinical experience is still required to assess and further refine generated algorithms.

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

[Spectral Characteristics and Sources of Dissolved Organic Matter in Inflow Rivers of Baiyangdian Lake Water in Summer Flood Season].

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

Nano-cutting mechanism of ion implantation-modified SiC: reducing subsurface damage expansion and abrasive wear.

This study utilized ion implantation to modify the material properties of silicon carbide (SiC) to mitigate subsurface damage during SiC machining. The paper analyzed the mechanism of hydrogen ion implantation on the machining performance of SiC at the atomic scale. A molecular dynamics model of nanoscale cutting of an ion-implanted SiC workpiece using a non-rigid regular tetrakaidecahedral diamond abrasive grain was established. The study investigated the effects of ion implantation on crystal structure phase transformation, dislocation nucleation, and defect structure evolution. Results showed ion implantation modification decreased the extension depth of amorphous structures in the subsurface layer, thereby enhancing the surface and subsurface integrity of the SiC workpiece. Additionally, dislocation extension length and volume within the lattice structure were lower in the ion-implanted workpiece compared to non-implanted ones. Phase transformation, compressive pressure, and cutting stress of the lattice in the shear region per unit volume were lower in the ion-implanted workpiece than the non-implanted one. Taking the diamond abrasive grain as the research subject, the mechanism of grain wear under ion implantation was explored. Grain expansion, compression, and atomic volumetric strain wear rate were higher in the non-implanted workpiece versus implanted ones. Under shear extrusion of the SiC workpiece, dangling bonds of atoms in the diamond grain were unstable, resulting in graphitization of the diamond structure at elevated temperatures. This study established a solid theoretical and practical foundation for realizing non-destructive machining at the atomic scale, encompassing both theoretical principles and practical applications. .

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Prognostic Molecular Biomarkers in Breast Cancer Lesions with Non-Mass Enhancement on MR.

Clustered ring enhancement (CRE) is a new lexicon for non-mass enhancement (NME) of breast MR in the 5th BIRADS, indicating a high suspicion of malignancy. We wonder if the presence of CRE correlates with expression of prognostic molecular biomarkers of breast cancer. A total of 58 breast lesions, which MRI reported with NME, were collected between July 2013 and December 2018. The patterns of enhancement including CRE were reviewed and the pathological results with expression of molecular biomarkers were collected. The association between MRI NME, pathological, and IHC stain findings were investigated under univariate analysis. A total of 58 breast lesions were pathologically proven to have breast cancer, comprising 31 lesions with CRE and 27 lesions without CRE on breast MRI. The expression of the estrogen receptor (ER) (p = 0.017) and the progesterone receptor (PR) (p = 0.017) was significantly lower in lesions with CRE as compared with those without CRE. The expression of Ki-67 (≥25%) was significantly higher in lesions with CRE (p = 0.046). The lesions with CRE had a lower expression ratio of ER (50.71 ± 45.39% vs. 74.26 ± 33.59%, p = 0.028). Our study indicated that lesions with CRE may possess different features from those without CRE in molecular expression, bearing a more aggressive behavior.

Evolution Path of Precursor-Induced High-Temperature Lithiation Reaction during the Synthesis of Lithium-Rich Cathode Materials.

High-temperature lithiation is one of the crucial steps for the synthesis of Li- and Mn-rich layered metal oxide (LMLO) cathodes. A profound insight of the micromorphology and crystal structure evolution during calcination helps to realize the finely controlled preparation of final cathodes, finally achieving a desired electrochemical performance. In this work, two typical precursors (hydroxide and oxalate) were selected to prepare LMLO. It is found that the influence of the lithium source on reaction pathways is determined by the properties of precursors. In the case of hydroxide as a precursor, whatever lithium sources it is, the flake morphology of LMLO is inherited from hydroxide precursors. This is because the crystal structure of cathode products has a high similarity with its precursor in terms of the oxygen array arrangement, and the topological transformation occurs from hydroxide (P-3ml) to LMLOs (C/2m and R3m). Thus, the morphology and microstructure of LMLO cathodes could be well controlled only by tuning the properties of hydroxide precursors. Conversely, the decomposition of a lithium source has a great influence on the intermediate transformation when oxalate is used as the precursor. This is because a large amount of CO2 is released from the oxalate precursor after the decomposition reaction, resulting in drastic structural changes. At this time, the diffusion ability of the lithium source leads to the competition between the spinel phase and layered phase. Based on this point, the formation of a spinel intermediate phase can be reduced by accelerating the decomposition of the lithium source, contributing to the generation of a highly pure layered phase, thus exhibiting higher electrochemical performance. These insights provide an exciting cue to the rational selection and design of raw materials and lithium sources for the controlled synthesis of LMLO cathodes.