Comparison of efficacy and safety of conventional transarterial chemoembolization and drug-eluting bead transarterial chemoembolization in unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD: Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS: A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS: Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.

Layered BaV6O16·3H2O@GO as a high performance cathode material for calcium ion batteries.

The lack of suitable cathode materials has hampered the further development of calcium-ion batteries (CIBs). A novel composite cathode material, namely BaV6O16·3H2O@GO, was fabricated, which delivers a high specific capacity of 285.72 mA h g-1 at 50 mA g-1 after 50 cycles and a long cycle life, benefiting from a large layer spacing and robust structure. This study provides guidance for the development of vanadium-based cathode materials for CIBs.

Transcatheter arterial chemoembolization of apatinib and camrelizumab (SHR1210) against liver metastasis from hepatic neuroendocrine tumor: a case report.

In this case report, we present the case of a 46-year-old woman with a hepatic neuroendocrine tumor (NET G2)-induced liver metastases. Initially, the left lateral lobectomy of the liver was performed. The post-operative pathological examination revealed NET G2, leading to the post-operative recovery with a general review. Further, the re-examination of liver magnetic resonance imaging (MRI) showed post-operative changes in the tumor of the left lateral lobe, with multiple liver masses and possible metastasis. Thus, the liver interventional therapy and apatinib-based targeted therapy based on the "camrelizumab + apatinib" regimen were performed, respectively. The 20-month follow-up indicated a slightly increased hepatic hilum and retroperitoneal lymph nodes, accompanied by hand-foot syndrome. Eventually, the overall condition continued to relieve, indicating that the combined treatment could substantially improve the NET G2 conditions-associated liver metastasis.

Systemic chemotherapy plus transarterial chemoembolization versus systemic chemotherapy alone for unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.

PURPOSE: Systemic chemotherapy (SYS) is the first-line treatment of unresectable intrahepatic cholangiocarcinoma (ICC). However, the survival benefit of SYS is still limited. This study compared the efficacy and safety of patients with unresectable ICC treated with transarterial chemoembolization (TACE) plus SYS to SYS alone. MATERIAL AND METHODS: The multicenter retrospective cohort study included patients aged ≥ 18 years old with pathologically diagnosed ICC. Patients with unmeasurable lesions, not receiving SYS treatment, Child-Pugh grade C, Eastern Cooperative Oncology Group performance status score of 3 or higher, prior liver resection, incomplete medical information, or discontinuation of the first SYS treatment were excluded. Data collection was mainly from the hospital system, and the survival outcome of patients was obtained through follow-up. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score matching at a 1:1 ratio using the nearest neighbor matching algorithm was performed to reduce selection bias between the TACE plus SYS and SYS alone groups. The Cox proportional hazards model was used to identify prognostic factors associated with OS and to estimate their hazard ratios. Modified Response Evaluation Criteria in Solid Tumors criteria were utilized to evaluate the response of tumors to therapy. RESULTS: Between June 2016 and February 2023, 118 unresectable ICC patients from three hospitals were included in this study. Of them, 37 were in the TACE plus SYS group and 81 were in the SYS alone group. The median OS in the combination group was 11.3 months, longer than the 6.4 months in the SYS alone group (P = 0.011). A greater objective response rate (ORR) and disease control rate (DCR) were observed in the combination group than in the SYS alone group (ORR, 48.65 vs. 6.17%, P < 0.001; DCR, 89.19 vs. 62.96%, P = 0.004). There were 16 patients in each group after matching, and the matched results remained consistent regarding OS and tumor response. Adverse events (AEs) were similar in the two groups after matching. CONCLUSION: Compared to SYS alone, the combination treatment of TACE plus SYS was more effective than SYS alone in improving OS, ORR, and DCR without any significant increase in AEs. TACE plus SYS may be a viable treatment option for patients with unresectable ICC.

Oxygen Vacancy-Enhanced Centrosymmetric Breaking of SrFeO3- x for Piezoelectric-Catalyzed Synthesis of H2O2.

Normally, only noncentrosymmetric structure of the materials can potentially be piezoelectric. Thus, it is limited in the field of piezoelectricity for the centrosymmetric structure of the material. In this work, the performance of piezoelectricity is successfully achieved from centrosymmetric SrFeO3- x by modulating oxygen vacancies, which have a surface piezoelectric potential up to 93 mV by using Kelvin-probe force microscopy (KPFM). Moreover, the piezoelectric effects of SrFeO3- x are also evaluated by piezoelectric catalytic effect and density functional theory calculations (DFT). The results show that the piezo-catalytic degradation of tetracycline reaches 96% after 75 min by ultrasonic mechanical vibration and the production of H2O2 by SrFeO3- x piezoelectric synthesis could reach 1821 µmol L-1. In addition, the DFT results indicate that the intrinsic effect of oxygen vacancies effectively promotes the adsorption and activation of O2 and H2O as well as intermediates and improves the piezoelectric catalytic activity. This work provides an effective basis for realizing the piezoelectricity of centrosymmetric materials and regulating the development of piezoelectric catalytic properties.

Enhancement of pyranoanthocyanin formation in blueberry wine with non-Saccharomyces yeasts.

The development of blueberry wine provides an alternative method for maintaining the nutritional value and extending the shelf life of blueberries. However, anthocyanin loss and off-flavor compound generation during fermentation impair blueberry wine color and quality. Hydroxycinnamate decarboxylase from yeast can catalyze the conversion of hydroxycinnamic acids to vinylphenols, which later may condense with anthocyanins to form more stable vinylphenolic pyranoanthocyanins. In this study, 10 non-Saccharomyces yeasts from Daqu that showed hydroxycinnamate decarboxylase activity were screened. Among the 10 strains, Wickerhamomyces anomalus Y5 showed the highest consumption (34.59%) of the total tested phenolic acids and almost no H2S production. Furthermore, Y5 seemed to produce four vinylphenol pyranoanthocyanins (cyanidin-3-O-galactoside/glucoside-4-vinylcatechol, cyanidin-3-O-galactoside/glucoside-4-vinylsyringol, malvidin-4-vinylguaiacol, and malvidin-4-vinylcatechol) during blueberry wine fermentation, which may improve the color stability of blueberry wine. These findings provide new insights for improving the quality of blueberry wine using non-Saccharomyces yeasts.

Application of a Radiomics Machine Learning Model for Differentiating Aldosterone-Producing Adenoma from Non-Functioning Adrenal Adenoma.

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734-1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic-Radscore model had an AUC of 0.994 [95% CI, 0.978-1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma.

Recent Advances of Enzymes in the Food Industry.

Enzymes used in the food industry are obtained from plants, animals, or microorganisms [...].

Sensorineural hearing loss induced by gefitinib: A CARE-compliant case report and literature reviews.

RATIONALE: Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7. PATIENT CONCERNS: An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness. DIAGNOSES: The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. INTERVENTIONS: The otolaryngologist recommended bilateral hearing aids to enhance hearing function. OUTCOMES: Throughout our follow-up period, the patient did not receive a hearing aid implant. LESSONS: This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes.

Pressure-induced superconductivity of Ac-B-H hydrides.

The search for room-temperature superconductors among high-pressure hydrides is a hot research topic. In this study, the structures, stabilities and superconducting properties of ternary Ac-B-H hydrides were studied using a genetic algorithm (GA) combined with density functional theory (DFT) calculations. It was shown that the R3̄m-AcBH8 and I4/mmm-AcB2H8 structures were thermodynamically and dynamically stable above 70 and 125 GPa, respectively. In the R3̄m-AcBH8 structure, the BH6 unit and the dispersed H atoms were bonded to form a corrugated structure. The I4/mmm-AcB2H8 structure contained a cage and the Ac atom located at the cage center. The calculations of the electron-phonon coupling showed that the R3̄m-AcBH8 and I4/mmm-AcB2H8 structures had Tc values of 140 K (70 GPa) and 99 K (125 GPa), respectively. The analyses of the phonon dispersion curves revealed that electron-phonon coupling was closely related to the vibrations of the B-H bonds.

[Protopanaxadiol-type ginsenoside hydrolases and their application in the preparation of ginsenoside Compound K: a review].

Ginsenoside Compound K (CK) has anti-cancer and anti-inflammatory pharmacological activities. It has not been isolated from natural ginseng and is mainly prepared by deglycosylation of protopanaxadiol. Compared with the traditional physicochemical preparation methods, the preparation of CK by hydrolysis with protopanaxadiol-type (PPD-type) ginsenoside hydrolases has the advantages of high specificity, environmental-friendliness, high efficiency and high stability. In this review, the PPD-type ginsenoside hydrolases were classified into three categories based on the differences in the glycosyl-linked carbon atoms of the hydrolase action. It was found that most of the hydrolases that could prepare CK were PPD-type ginsenoside hydrolase type Ⅲ. In addition, the applications of hydrolases in the preparation of CK were summarized and evaluated to facilitate large-scale preparation of CK and its development in the food and pharmaceutical industries.

Combinatorial Enzymatic Catalysis for Bioproduction of Ginsenoside Compound K.

Ginsenoside compound K (CK) is an emerging functional food or pharmaceutical product. To date, there are still challenges to exploring effective catalytic enzymes for enzyme-catalyzed manufacturing processes and establishing enzyme-catalyzed processes. Herein, we identified three ginsenoside hydrolases BG07 (glucoamylase), BG19 (ß-glucosidase), and BG23 (ß-glucosidase) from Aspergillus tubingensis JE0609 by transcriptome analysis and peptide mass fingerprinting. Among them, BG23 was expressed in Komagataella phaffii with a high volumetric activity of 235.73 U mL-1 (pNPG). Enzymatic property studies have shown that BG23 is an acidic (pH adaptation range of 4.5-7.0) and mesophilic (thermostable < 50 °C) enzyme. Moreover, a one-pot combinatorial enzyme-catalyzed strategy based on BG23 and BGA35 (ß-galactosidase from Aspergillus oryzae) was established, with a high CK yield of 396.7 mg L-1 h-1. This study explored the ginsenoside hydrolases derived from A. tubingensis at the molecular level and provided a reference for the efficient production of CK.

High-Value Bioconversion of Ginseng Extracts in Betaine-Based Deep Eutectic Solvents for the Preparation of Deglycosylated Ginsenosides.

Deep eutectic solvents (DES), as a green alternative to traditional organic solvents in biocatalysis, not only activate proteins but even increase the efficiency of enzymatic reactions. Here, DES were used in a combinatorial enzyme-catalyzed system containing ß-glucosidase BGLAt and ß-galactosidase BGALAo to produce deglycosylated ginsenosides (De-g) from ginseng extracts (GE). The results showed that DES prepared with betaine and ethylene glycol (molar ratio, 1:2) could significantly stimulate the activity of the combinatorial enzymes as well as improve the acid resistance and temperature stability. The DES-based combinatorial enzyme-catalyzed system could convert 5 g of GE into 1.24 g of De-g (F1, F2, 20 (S)-PPT, and CK) at 24 h, which was 1.1 times that of the buffer sample. As confirmed by the spectral data, the changes in the conformations of the combinatorial enzymes were more favorable for the binding reaction with the substrates. Moreover, the constructed DES-based aqueous two-phase system enabled the recovery of substantial amounts of DES and De-g from the top phase. These results demonstrated that DES shows great application as a reaction solvent for the scale-up production of De-g and provide insights for the green extraction of natural products.

Has_circ_0048764 promotes breast cancer progression by sponging miR-578 and regulating HMGA2 expression.

BACKGROUND: Circular RNAs (circRNAs) function as important regulators in the progression of cancers. The role of circRNA_0048764 (circ_0048764) in the development of breast cancer (BC) remains inconclusive. This work investigates the biological function and molecular mechanism of circ_0048764 in BC. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression levels of circ_0048764, microRNA-578 (miR-578) and high mobility group AT-hook 2 (HMGA2) mRNA. The viability of BC cells was examined by cell counting kit 8 (CCK-8) assay. Besides, cyclin D1, proliferating cell nuclear antigen (PCNA) and HMGA2 expression levels were detected by western blot. The migrative and invasive capability of BC cells were probed by transwell assay. The relationships between miR-578 and circ_0048764 or HMGA2 3'-UTR were validated by dual-luciferase reporter gene assay. RESULTS: Circ_0048764 was highly expressed in BC tissues and cells, which was significantly associated with tumor size (≥2 cm), lymph node status (positive), and higher TNM stage of BC patients. Circ_0048764 depletion suppressed the proliferative, migrative, and invasive abilities of BC cells, which was rescued by transfection of miR-578 inhibitors. The binding sites were verified between circ_0048764 and miR-578. HMGA2 was identified to be a target of miR-578 in BC cells, and circ_0048764 positively regulated HMGA2 expression in BC cells via repressing miR-578. CONCLUSION: Circ_0048764 promotes BC cell growth, migration and invasion via absorbing miR-578 and up-regulating HMGA2.

Co-60 gamma irradiation induced ovalbumin-glucose glycation and allergenicity reduction revealed by high-resolution mass spectrometry and ELISA assay.

Ovalbumin (OVA)-glucose mixture was treated with Co-60 irradiation at 0-25 kGy, and effects of irradiation on the glycation and allergenicity of OVA were investigated. Irradiation induced glycation between OVA and glucose, reflected in the significant increase of glycation sites from 3 to 14. Interestingly, OVA irradiated at 25 kGy had three new glycated peptides (568.782+, 739.382+ and 509.752+). The degree of substitution per peptide molecule (DSP) of glycated peptides exhibited different trends with increasing irradiation dose. Particularly, glycated peptides 17-26, 55-60, 263-267 and 368-375 showed markedly decreased DSP values after irradiation at 20 and 25 kGy, which could be caused by the generation of Maillard reaction products (MRPs). MS/MS spectra suggested that neutral loss occurred in glycated arginine, whose structure was similar to MRPs. The IgG- and IgE-binding abilities of OVA significantly decreased with increasing irradiation dose, indicating that the protein allergenicity was reduced.

Phosphorylation of ovalbumin after pulsed electric fields pretreatment: Effects on conformation and immunoglobulin G/immunoglobulin E-binding ability.

Ovalbumin (OVA) is one of major allergens of hen egg white with excellent nutritional and processing properties. Previous research exhibits that pulsed electric field (PEF) treatment could partially unfold OVA. This may contribute to the improvement of OVA phosphorylation. In this study, the effect of PEF pretreatment combined with phosphorylation on the structure and immunoglobulin (Ig) G/IgE-binding ability of OVA was investigated. The structural changes were measured by circular dichroism (CD), ultraviolet absorption, and fluorescence spectroscopy. The IgG- and IgE-binding abilities were determined by inhibition enzyme-linked immunosorbent assay (ELISA) using rabbit polyclonal antibodies and egg-allergy patients' sera, respectively. The results showed that PEF pretreatment combined with phosphorylation markedly reduced the IgG- and IgE-binding abilities. It was attributed to the changes in secondary and tertiary structure, which was reflected in the increase of ultraviolet (UV) absorbance, α-helix content, and the increase the molecular weight. Moreover, it suggested PEF pretreatment improved the phosphorylation of OVA and enhanced the reduction of IgG/IgE-binding capacity of phosphorylated OVA. Therefore, PEF pretreatment combined with phosphorylation has the potential for developing a method for OVA desensitization.

Extending the capabilities of intact-mass analyses to monoclonal immunoglobulins of the E-isotype (IgE).

Mass spectrometry (MS) has become an indispensable tool in structural characterization and quality control of monoclonal antibodies (mAbs). Intact-mass analysis is a particularly attractive option that provides a powerful and cost-effective means to not only confirm the structural integrity of the protein, but also probe its interactions with therapeutic targets. To a certain extent, this success can be attributed to relatively modest glycosylation levels exhibited by IgG molecules, which limits their structural heterogeneity and enables straightforward mass measurements at the intact molecule level. The recent surge of interest in expanding the repertoire of mAbs to include other classes of immunoglobulins places a premium on efforts to adapt the IgG-tailored experimental strategies to other classes of antibodies, but their dramatically higher levels of glycosylation may create insurmountable obstacles. The monoclonal murine IgE antibody explored in this work provides a challenging model system, as its glycosylation level exceeds that of conventional IgG mAbs by a factor of nine. The commercial sample, which included various IgE fragments, yields a poorly resolved ionic signal in intact-mass measurements, from which little useful information can be extracted. However, coupling MS measurements with the limited charge reduction of select polycationic species in the gas phase gives rise to well-defined charge ladders, from which both ionic masses and charges can be readily determined. The measurements reveal significant variation of the extent of glycosylation within intact IgE molecules, as well as the presence of low-molecular weight impurities in the commercial IgE sample. Furthermore, incubation of the monoclonal IgE with its antigen (ovalbumin) gives rise to the formation of complexes with varying stoichiometries, which can also be uniquely identified using a combination of native MS, limited charge reduction in the gas phase and data fitting procedures. This work demonstrates that following appropriate modifications, intact-mass analysis measurements can be successfully applied to mAbs beyond the IgG isotype, providing a wealth of information not only on the mass distribution of the intact IgE molecules, but also their large-scale conformational integrity, the integrity of their covalent structure, and their interactions with antigens.

Targeting Glutamine Metabolism Ameliorates Autoimmune Hepatitis via Inhibiting T Cell Activation and Differentiation.

Background: Autoimmune hepatitis (AIH) is mediated by a cascade of T cell-mediated events directed at liver cells and persistent inflammation within the liver can eventually result in liver cirrhosis. Targeting glutamine metabolism has an impact on T cell activation and differentiation. However, the effect of glutamine metabolism blocking upon AIH remains unknown. We use glutaminase antagonist 6-diazo-5-oxo-L-norleucine (DON) for in vitro assays and its prodrug 2-(2-amino-4-methylpentanamido)-DON (JHU083) for in vivo assays to investigate the potential therapeutic effect and molecular mechanism of glutamine metabolism blocking in an AIH murine model. Methods: AIH mice were treated with JHU083 or vehicle before concanavalin A (ConA) administration, and disease severity was examined. Then activation and differentiation [including Th1/Th17 cells and cytotoxic T lymphocytes (CTL)] of T cells from Vehicle-WT, JHU083-AIH and Vehicle-AIH mice were tested. Furthermore, in vitro T cell activation and differentiation were measured using separated splenocytes stimulated with ConA with or without DON. The activation and differentiation of T cells were tested using flow cytometry, qRT-PCR and ELISA. Phosphorylation level of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (P70S6K) were examined by western blotting. Results: JHU083 and DON significantly suppressed the activation of T cells and inhibited the differentiation of Th1/Th17 cells and CTL in vivo and in vitro. Besides, we demonstrated that glutamine metabolism blocking inhibited T cells activation and differentiation through decreasing the mRNA expression of amino acid transporter solute carrier family 7 member 5 (SLC7A5) and mitigating the activation of mTOR signaling. Conclusions: We proved that targeting glutamine metabolism represents a potential new treatment strategy for patients with AIH and other T cell-mediated disease. Mechanistically, we demonstrated that glutamine metabolism blocking inhibits T cells activation and suppresses the differentiation of Th1/Th17 cells and CTL.

Multi-input convolutional network for ultrafast simulation of field evolvement.

There is a compelling need for the regression capability of mapping the initial field and applied conditions to the evolved field, e.g., given current flow field and fluid properties predicting next-step flow field. Such a capability can provide a maximum to full substitute of a physics-based model, enabling fast simulation of various field evolvements. We propose a conceptually simple, lightweight, but powerful multi-input convolutional network (ConvNet), yNet, that merges multi-input signals by manipulating high-level encodings of field/image input. yNet can significantly reduce the model size compared with its ConvNet counterpart (e.g., to only one-tenth for main architecture of 38-layer depth) and is as much as six orders of magnitude faster than a physics-based model. yNet is applied for data-driven modeling of fluid dynamics, porosity evolution in sintering, stress field development, and grain growth. It consistently shows great extrapolative prediction beyond training datasets in terms of temporal ranges, spatial domains, and geometrical shapes.