Effect of Ethanol Extract of Tea on the Microstructural Features and Retrogradation Characteristics of Glutinous Rice Starch.

The glutinous rice starch (GRS) regeneration process could lead to decreased product quality and shorter shelf life. The purpose of this study was to analyze the effect of an ethanol extract of tea (EET) on the regeneration properties of GRS. The microstructure of starch was determined via scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy was used to determine the microstructure of starch-polyphenol molecular groups, an X-ray diffraction (XRD) instrument was used to determine the starch crystal structure, a differential scanning calorimeter (DSC) was used to determine the thermodynamic properties of starch, and the inhibitory effect of EET on GRS regeneration was comprehensively evaluated. The effect of EET on the in vitro digestion properties of GRS was also determined. The results showed that the addition of EET in GRS resulted in an increase in solubility and swelling power and a decrease in crystallinity and ΔHr. Compared to the control group, when retrograded for 10 days, the ΔHr of GRS with 1%, 2.5%, 5%, and 10% addition of EET decreased by 34.61%, 44.53%, 52.93%, and 66.79%, respectively. Furthermore, the addition of EET resulted in a decrease in the content of RDS and an increase in the content of SDS and RS in GRS. It was shown that the addition of EET could significantly inhibit the retrogradation of GRS, improve the processability, and prolong the shelf life of GRS products.

Identification of Corn Peptides with Alcohol Dehydrogenase Activating Activity Absorbed by Caco-2 Cell Monolayers.

Alcohol dehydrogenase (ADH) plays a pivotal role in constraining alcohol metabolism. Assessing the ADH-activating activity in vitro can provide insight into the capacity to accelerate ethanol metabolism in vivo. In this study, ADH-activating peptides were prepared from corn protein meal (CGM) using enzymatic hydrolysis, and these peptides were subsequently identified following simulated gastrointestinal digestion and their absorption through the Caco-2 cell monolayer membrane. The current investigation revealed that corn protein hydrolysate hydrolyzed using alcalase exhibited the highest ADH activation capability, maintaining an ADH activation rate of 52.93 ± 2.07% following simulated gastrointestinal digestion in vitro. After absorption through the Caco-2 cell monolayer membrane, ADH-activating peptides were identified. Among them, SSNCQPF, TGCPVLQ, and QPQQPW were validated to possess strong ADH activation activity, with EC50 values of 1.35 ± 0.22 mM, 2.26 ± 0.16 mM, and 2.73 ± 0.13 mM, respectively. Molecular Docking revealed that the activation of ADH occurred via the formation of a stable complex between the peptide and the active center of ADH by hydrogen bonds and hydrophobic interactions. The results of this study also suggest that corn protein hydrolysate could be a novel functional dietary element that helps protects the liver from damage caused by alcohol and aids in alcohol metabolism.

RNF125­mediated ubiquitination of MCM6 regulates the proliferation of human liver hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Minichromosome maintenance proteins (MCMs), particularly MCM2-7, are upregulated in various cancers, including HCC. The aim of the present study was to investigate the role of MCM2-7 in human liver HCC (LIHC) and the regulation of the protein homeostasis of MCM6 by a specific E3 ligase. Bioinformatics analyses demonstrated that MCM2-7 were highly expressed in LIHC compared with corresponding normal tissues at the mRNA and protein levels, and patients with LIHC and high mRNA expression levels of MCM2, MCM3, MCM6 and MCM7 had poor overall survival rates. Cell Counting Kit-8 and colony formation assays revealed that the knockdown of MCM2, MCM3, MCM6 or MCM7 in Huh7 and Hep3B HCC cells inhibited cell proliferation and colony formation. In addition, pull-down, co-immunoprecipitation and ubiquitination assays demonstrated that RNF125 interacts with MCM6 and mediates its ubiquitination. Furthermore, co-transfection experiments indicated that RNF125 promoted the proliferation of HCC cells mainly through MCM6. In summary, the present study suggests that the RNF125-MCM6 axis plays an important role in the regulation of HCC cell proliferation and is a promising therapeutic target for the treatment of LIHC.

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production.

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice. Five-dose δ-T3H was utilized as the optimal therapeutic regimen due to long-term G-CSF production and the best peripheral blood (PB) recovery of irradiated mice. Comparable with rhG-CSF, sequential administration of δ-T3H post-irradiation improved hematologic recovery and accelerated the regeneration of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow (BM) and spleen of 6.5Gy irradiated mice; and consistently enhanced repopulation of BM-HSCs. In 4.0Gy irradiated nonhuman primates, δ-T3H exhibited comparable efficacy as rhG-CSF to promote PB recovery and colony-formation of BM-HPCs. Altogether, we demonstrated that sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production, indicated δ-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

Purification, identification and molecular docking of dual-functional peptides derived from corn protein hydrolysates with antioxidant and antiadhesive activity against Helicobacter pylori.

BACKGROUND: More than 50% of the world's population is infected with Helicobacter pylori, which is classified as a group I carcinogen by the World Health Organization (WHO). RESULTS: Corn protein dual-functional peptides were identified and functionally analyzed in vitro and in silico. Two novel dual-functional peptides were identified as Cys-Gln-Asp-Val-Pro-Leu-Leu (CQDVPLL, CQ7) and Thr-Ile-Phe-Pro-Gln-Cys (TIFPQC, TI6) using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS). The antiadhesive effects against H. pylori of CQ7 and TI6 were 45.17 ± 2.41% and 48.62 ± 1.84% at 4 mg mL-1 , respectively. In silico prediction showed that CQ7 and TI6 had good physicochemical properties. Molecular docking demonstrated that CQ7 and TI6 could bind to the adhesins BabA and SabA by hydrophobic interactions and hydrogen bonds, preventing H. pylori infection. Moreover, CQ7 showed strong antioxidant activity due to its unique amino acid composition. CONCLUSION: The present study demonstrated that the identified peptides, CQ7 and TI6, possess antioxidant and antiadhesive effects, preventing H. pylori infection and alleviating oxidative injury to the gastric mucosa. © 2023 Society of Chemical Industry.

A highly sensitive and anti-freezing conductive strain sensor based on polypyrrole/cellulose nanofiber crosslinked polyvinyl alcohol hydrogel for human motion detection.

Electro-conductive hydrogels emerge as a stretchable conductive materials with diverse applications in the synthesis of flexible strain sensors. However, the high-water content and low cross-links density cause them to be mechanically destroyed and freeze at subzero temperatures, limiting their practical applications. Herein, we report a one-pot strategy by co-incorporating cellulose nanofiber (CNF), Poly pyrrole (PPy) and glycerol with polyvinyl alcohol (PVA) to prepare hydrogel. The addition of PPy endowed the hydrogel with good conductivity (∼0.034 S/m) compared to the no PPy@CNF group (∼0.0095 S/m), the conductivity was increased by 257.9 %. The hydrogel exhibits comparable ionic conductivity at -18 °C as it does at room temperature. It's attributed to the glycerol as a cryoprotectant and the formation of hydrated [Zn(H2O)n]2+ ions via strong interaction between Zn2+ and water molecules. Moreover, the cellulose nanofiber intrinsically assembled into unique hierarchical structures allow for strong hydrogen bonds between adjacent cellulose and PPy polymer chains, greatly improve the mechanical strength (stress∼0.65 MPa, strain∼301 %) and excellent viscoelasticity (G'max âˆ¼ 82.7 KPa). This novel PPy@CNF-PVA hydrogel exhibits extremely high Gauge factor (GF) of 2.84 and shows excellent sensitivity, repeatability and stability. Therefore, the hydrogel can serve as reliable and stable strain sensor which shows excellent responsiveness in human activities monitoration.

[Clinical Characteristics and Correlation with Prognosis of DLBCL with Bone Marrow Involvement and Chromosomal Abnormalities].

OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and chromosome abnormalities, and further analyze the correlation between the degree of chromosome abnormality and prognosis. METHODS: The clinical data of 88 patients diagnosed with DLBCL with bone marrow involvement and complete chromosomal findings in Shanxi Province Cancer Hospital were retrospectively analyzed. The χ2 test was used to analyze their clinical characteristics, and the Kaplan-Meier method was used in PFS and OS, and log-rank method in comparison. RESULTS: Chromosome abnormalities were detected in 31 of the 88 patients(35.2%), 15 of whom had complex karyotype(17.0%). The positive rate of BCL-2, BCL-6, C-MYC and Ki-67≥80% was high in patients with complex karyotype, and most of them are double expressor lymphoma. Survival analysis showed that patients with complex karyotype of DLBCL had poorer PFS and OS compared to those with normal karyotype and 1-2 chromosomal abnormalities. CONCLUSION: In DLBCL patients with bone marrow involvement and chromosome abnormalities, patients with complex karyotype have a shorter survival time.

Preparation of Corn Peptides with Anti-Adhesive Activity and Its Functionality to Alleviate Gastric Injury Induced by Helicobacter pylori Infection In Vivo.

More than 50% of the world population is infected with Helicobacter pylori (H. pylori), which is classified as group I carcinogen by the WHO. H. pylori surface adhesins specifically recognize gastric mucosal epithelial cells' (GES-1 cells) receptor to complete the adhesion. Blocking the adhesion with an anti-adhesion compound is an effective way to prevent H. pylori infection. The present study found that corn protein hydrolysate, hydrolyzed by Neutral, effectively alleviated gastric injury induced by H. pylori infection through anti-adhesive and anti-inflammatory effects in vitro and in vivo. The hydrolysate inhibited H. pylori adhesion to GES-1 cells significantly, and its anti-adhesive activity was 50.44 ± 0.27% at 4 mg/mL, which indicated that the hydrolysate possessed a similar structure to the GES-1 cells' receptor, and exhibited anti-adhesive activity in binding to H. pylori. In vivo, compared with the H. pylori infection model group, the medium and high dose of the hydrolysate (400-600 mg/kg·bw) significantly decreased (p < 0.05) the amount of H. pylori colonization, pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α and MPO), chemokines (KC and MCP-1) as well as key metabolites of NF-κB signaling pathway levels (TLR4, MyD88 and NF-κB), and it increased antioxidant enzyme contents (SOD and GSH-Px) and the mitigation of H. pylori-induced pathological changes in the gastric mucosa. Taken together, these results indicated that the hydrolysate intervention can prevent H. pylori-induced gastric injury by anti-adhesive activity and inhibiting the NF-κB signaling pathway's induction of inflammation. Hence, the corn protein hydrolysate might act as a potential anti-adhesive agent to prevent H. pylori infection.

CD73 Dysregulates Monocyte Anti-Tumor Activity in Multiple Myeloma.

Purpose: Multiple myeloma (MM) is characterized by immune cell dysfunction in the tumor microenvironment (TME). We aimed at evaluating the effect of CD73, an overexpressed factor in some tumors, on anti-tumor immune function in the TME of MM. Patients and Methods: We analyzed the expression of CD73 in T-, B-, and natural killer (NK)-lymphocytes and monocytes in bone marrow (BM), peripheral blood (PB) from MM patients and healthy controls, and residual CD138+ cells using flow cytometry. The anti-tumor activity of these monocytes was confirmed by co-culture with RPMI-8226 cells treated with a CD73 inhibitor. We determined the interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ levels using a cytometric bead array. Monocyte phagocytosis in cell culture sediment was then observed and measured. Results: CD73 was highly expressed in T-, B-, and NK-lymphocytes and monocytes from the BM and PB isolated from patients with MM. Compared with healthy controls, MM samples exhibited significantly higher CD73 expression and TNF-α, IFN-γ, IL-10 levels in monocytes. Inhibiting CD73 in BM immune cells from MM samples significantly increased the secretion of IL-2, TNF-α, and IFN-γ, as well as the killing ability of immune cells. However, monocyte phagocytosis was seldom observed. Inhibiting CD73 in MM monocytes significantly increased the secretion of IL-2, TNF-α, and IFN-γ in monocytes and improved monocyte killing and phagocytosis. Conclusion: Monocytes from MM exhibited weakened anti-tumor effects, and CD73 was involved in forming an immunosuppressive microenvironment. Inhibiting CD73 partly restored the anti-tumor activity of monocytes, a potential strategy for the treatment of MM.

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade.

Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.

Comparison of CT-guided thoracic sympathetic nerve block and radiofrequency in the treatment of primary palmar hyperhidrosis.

Background: Primary palmar hyperhidrosis (PPH) is a condition marked by an overactive secretion of the hand's exocrine glands and is frequently hereditary. The profuse sweating associated with this condition can significantly impair the patient's daily activities and quality of life. Objective: The objective of this study was to compared the benefits and drawbacks of thoracic sympathetic block and thoracic sympathetic radiofrequency in the treatment of PPH. Methods: A retrospective analysis was conducted on 69 patients. They were divided into groups A and B according to their treatment. Group A (34 cases) received CT-guided percutaneous thoracic sympathetic nerve chain anhydrous alcohol chemical damage block, and group B (35 cases) received CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency thermocoagulation. Results: Palmar sweating disappeared immediately after the operation. The recurrence rates at 1, 3, 6, 12, 24, and 36 months were 5.88% vs. 2.86% (P > 0.05), 20.59% vs. 5.71% (P > 0.05), 32.35% vs. 11.43% (P < 0.05),32.35% vs. 11.43% (P < 0.05), 25% vs. 14.71% (P < 0.05), and 68.75% vs. 20.59% (P < 0.05), respectively. The incidence of intercostal neuralgia and compensatory hyperhidrosis was higher in group A compared with of group B (52.94% vs. 22.86%, P < 0.05; 55.88% vs. 22.86%, P < 0.05). Conclusion: Both methods were found to be effective in treating PPH, but thoracic sympathetic radiofrequency had a longer-term effect, a lower recurrence rate, and a lower incidence of intercostal neuralgia and compensatory hyperhidrosis than a thoracic sympathetic block.

Application of circulating tumour DNA in terms of prognosis prediction in Chinese follicular lymphoma patients.

Background: Follicular lymphoma (FL), an indolent non-Hodgkin lymphoma (NHL), is generally incurable. Favourable prognosis and durable remission are crucial for FL patients. The genetic mutation spectrum provides novel biomarkers for determining the prognosis of FL patients, but its detection is easily affected by the collection of tumour tissue biopsies. In this study, we aimed to describe the mutational landscape of FL using circulating tumour DNA (ctDNA) samples and to explore the relationship between mutations and prognostic indicators of clinical outcome in patients with newly diagnosed follicular lymphoma and the prognostic value of such mutations. Methods: A total of 28 patients with newly diagnosed FL were included in this study. A targeted NGS-based 59-gene panel was used to assess the ctDNA mutation profiles. Differences in clinical factors between patients carrying mutations and those without mutations were analysed. We also explored the relationship between gene mutation status, mean VAFs (variant allele frequencies) and clinical factors. The Kaplan‒Meier method was applied to analyse the overall survival (OS) and progression-free survival (PFS) of patients carrying mutations and those without mutations. Results: ctDNA mutations were detectable in 21 (75%) patients. The most commonly mutated genes were CREBBP (54%, 15/28), KMT2D (50%, 14/28), STAT6 (29%, 8/28), CARD11 (18%, 5/28), PCLO (14%, 4/28), EP300 (14%, 4/28), BCL2 (11%, 3/28), and TNFAIP3 (11%, 3/28), with a mutation frequency of >10%. Patients with detectable ctDNA mutation tended to present with advanced Ann Arbor stage (III-IV) (p = 0.009), high FLIPI risk (3-5) (p = 0.023) and severe lymph node involvement (No. of involved areas ≥5) (p = 0.02). In addition, we found that the mean VAF was significantly higher in patients with advanced Ann Arbor stage, high-risk FLIPI, elevated lactate dehydrogenase (LDH: 0-248U/L), advanced pathology grade, bone marrow involvement (BMI) and lymph node involvement. Additionally, KMT2D, EP300, and STAT6 mutations were associated with inferior PFS (p < 0.05). Conclusion: We described the ctDNA mutation landscapes in Chinese patients with newly diagnosed FL and found that ctDNA VAF means reflect tumour burden. Moreover, PFS was shorter in patients with KMT2D, EP300 and STAT6 mutations.

Amino acid modified OCMC-g-Suc-ß-CD nanohydrogels carrying lapatinib and ginsenoside Rg1 exhibit high anticancer activity in a zebrafish model.

Nanohydrogels show great potential as efficient drug carriers due to their biocompatibility, low toxicity, and high water absorbability. In this paper, we prepared two O-carboxymethylated chitosan (OCMC)-based polymers functionalized with ß-cyclodextrin (ß-CD) and amino acid. The structures of the polymers were characterized by Fourier Transform Infrared (FTIR) Spectroscopy. Morphological study was carried out on a Transmission Electron Microscope (TEM), and the results indicated that the two polymers had irregular spheroidal structure with some pores distributed on their surface. The average particle diameter was below 500 nm, and the zeta potential was above +30 mV. The two polymers were further used for preparing nanohydrogels loaded with anticancer drugs lapatinib and ginsenoside Rg1, and the resulting nanohydrogels showed high drug loading efficiency and pH-sensitive (pH = 4.5) drug release behavior. In vitro cytotoxicity investigation revealed that the nanohydrogels exhibited high cytotoxicity against lung cancer (A549) cells. In vivo anticancer investigation was performed in a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-kras V12) zebrafish model. The results showed that the synthesized nanohydrogels significantly inhibited the expression of EGFP-kras v12 oncogene in zebrafish liver, and the L-arginine modified OCMC-g-Suc-ß-CD nanohydrogels loading lapatinib and ginsenoside Rg1 showed the best results.

Novel Lanthanide-Based Metal-Organic Framework Isomer as a Double Ratiometric Fluorescent Probe for Vanillymandelic Acid.

The concentration of vanillymandelic acid (VMA) in urine is closely related with pheochromocytoma diagnosis. Thus, it is essential to develop more accurate and convenient fluorescence sensing strategies toward VMA. Until now, the design of double ratiometric detection methods for VMA was still in the unexplored stage. In this work, novel Ln3+-based metal-organic frameworks (QBA-Eu and QBA-Gd0.875Eu0.125) possessing dual emission peaks was fabricated successfully, which served as isomers of YNU-1 and exhibited more excellent water stability in fluorescence and structure than the ones of YNU-1. The formation of the complex between QBA ligands and VMA molecules via hydrogen bonds within QBA-Eu frameworks produced a new emission band centered at 450 nm and resulted in the decline of monomer emission intensity for QBA at 390 nm. Owing to the reduced energy gap [ΔE (S1 - T1)], the antenna effect was hampered and luminescence of Eu3+ ions also decreased. The developed double ratiometric (I615nm/I475nm, I390nm/I475nm) fluorescence sensors based on QBA-Eu and QBA-Gd0.875Eu0.125 possessed the advantages of fast response (4 min), low detection limits (0.58 and 0.51; 0.22 and 0.31 µM), and wide linear ranges (2-100 and 2-80 µM), which met the requirements of pheochromocytoma diagnosis. We also applied them to determine VMA in an artificial urine sample and diluted human urine sample and obtained satisfactory results. They will become prospective fluorescence sensing platforms for VMA.

Purification, Identification and Evaluation of Antioxidant Peptides from Pea Protein Hydrolysates.

Food-derived antioxidant peptides can be explored as natural antioxidants due to their potential health benefits. In this study, antioxidant peptides were isolated and purified from pea protein hydrolysates (PPH). The DPPH and ABTS radical scavenging activities were used as indexes to purify the antioxidant peptides by a series of purification steps including ultrafiltration, ion exchange chromatography, G25 gel filtration chromatography, and reversed-phase chromatography. Three novel antioxidant peptides YLVN, EEHLCFR and TFY were identified, which all exhibited strong antioxidant activity in vitro. EEHLCFR showed stronger DPPH scavenging activity with an IC50 value of 0.027 mg/mL. YLVN showed stronger ABTS scavenging activity with an IC50 value of 0.002 mg/mL and higher ORAC values of 1.120 ± 0.231 µmol TE/µmol, which is even better than that of GSH. Three novel antioxidant peptides significantly elevated LO2 cells viability even at the concentration of 0.025 mg/mL, and cell viability enhanced to 53.42 ± 1.19%, 55.78 ± 1.03%, and 51.09 ± 1.06% respectively, compared to that of H2O2 injury group (48.35 ± 0.96%), and prevented the accumulation of ROS by enhancing the activities of antioxidant enzymes in H2O2-induced oxidative stress LO2 cells. The molecular docking results showed that the potential molecular mechanism of the three novel antioxidant peptides may be in high correlation with the activation of the Keap1-Nrf2 pathway by occupying the Keap1-Nrf2 binding site. These results demonstrate that the three novel antioxidant peptides are potential natural antioxidants that can be devoted to medicine or functional food ingredients.

Fabrication and application of Zn5 functionalized copolymer monolithic column for pipette tip micro-solid phase extraction of 4 polycyclic aromatic hydrocarbons in edible oil.

The contamination of polycyclic aromatic hydrocarbons (PAHs) in edible oil is a health threat. Thus, trace analysis of PAHs is of high necessity. Based on the efficient adsorption of PAHs on Zn5 metal cluster, a Zn5 functionalized copolymer monolithic column was rationally designed for pipette tip micro-solid phase extraction (µ-SPE). The modified Zn5 improved the adsorption selectivity and capacity of the monolith for naphthalene, phenanthrene, fluoranthene and pyrene. Chemical doping and copolymerization stabilized the monolith with a long life. Under optimal extraction conditions, a µ-SPE-high performance liquid chromatography with ultraviolet detector method was established for the detection of 4 PAHs in edible oils. The method yielded detection ranges of 0.15-250 µg L-1 (R2 > 0.997), detection limits of 0.050-1.5 µg L-1, satisfactory recoveries (86.3-101.5 %), and high precisions (RSDs < 7.9 %). The results indicated that the Zn5 functionalized copolymer monolithic column was an ideal separation medium for the detection of PAHs residues in edible oils.

Novel amphiphilic hydroxyethyl starch-based nanoparticles loading camptothecin exhibit high anticancer activity in HepG2 cells and zebrafish.

Camptothecin is a naturally occurred anticancer drug but exhibits limitations including poor aqueous solubility, low bioavailability, and high level of adverse drug reactions on normal organs. To overcome these problems, this paper developed a novel amphiphilic Lau-Leu-HES carrier using hydroxyethyl starch, lauric acid, and L-leucine as starting materials. The carrier was successfully applied to prepare Lau-Leu-HES nanoparticles loading camptothecin. The drug loading efficiency and encapsulation efficiency of the nanoparticles were calculated to be 29.04% and 81.85%, respectively. The nanoparticles exhibited high zeta potential (-15.51 mV) and small hydrodynamic diameter (105.4 nm). Camptothecin in nanoparticles could be rapidly released under acidic condition (pH = 4.5), thereby indicating the high sensitivity under cancer microenvironments. Anticancer investigation revealed that the nanoparticles could inhibit the proliferation of HepG2 cells in vitro. Compared with commercial available drug doxorubicin, the nanoparticles could significantly inhibit the expression of krasv12 oncogene in transgenic Tg (EGFP-krasV12) zebrafish. These results indicate that the camptothecin-loaded Lau-Leu-HES nanoparticles are expected to be a potential candidate for cancer therapy.

Circulating tumor DNA mutation profile is associated with the prognosis and treatment response of Chinese patients with newly diagnosed diffuse large B-cell lymphoma.

Background: Characterization of gene mutation profiles can provide new treatment options for patients with diffuse large B-cell lymphoma (DLBCL). However, this method is challenged by the limited source of tissue specimens, especially those of DLBCL patients at advanced stages. Therefore, in the current study, we aimed to describe the gene mutation landscape of DLBCL using circulating tumor DNA (ctDNA) samples obtained from patients' blood samples, as well as to explore the relationship between ctDNA mutations and the prognosis and treatment response of patients with newly diagnosed DLBCL. Methods: A total of 169 newly diagnosed Chinese DLBCL patients were included in this study, among which 85 patients were divided into a training set and 84 were assigned into a validation set. The mutation profile of a 59-gene panel was analyzed by targeted next generation sequencing (NGS) of the patients' ctDNA samples. Differences in clinical factors between patients with and without ctDNA mutations were analyzed. In addition, we also explored gene mutation frequencies between GCB and non-GCB subtypes, and the relationship between gene mutation status, clinical factors, mean VAF (variant allele frequencies) and the patients' overall survival (OS) and progression-free survival (PFS). Results: ctDNA mutations were detected in 64 (75.3%) patients of the training set and 67 (79.8%) patients of the validation set. The most commonly mutated genes in both sets were PCLO, PIM1, MYD88, TP53, KMT2D, CD79B, HIST1H1E and LRP1B, with mutation frequencies of >10%. Patients with detectable ctDNA mutations trended to present advanced Ann Arbor stages (III-IV), elevated LDH (lactate dehydrogenase) levels, shorter OS and PFS, and a lower complete response (CR) rate to the R-CHOP regimen compared with DLBCL patients without ctDNA mutations. In addition, mean VAF (≥4.94%) and PCLO mutations were associated with poor OS and PFS. Conclusion: We investigated the ctDNA mutation landscape in Chinese patients with newly diagnosed DLBCL and found that ctDNA could reflect tumor burden and patients with detectable ctDNA mutations trended to have shorter OS and PFS and a lower CR rate.

A Novel Fermented Rapeseed Meal, Inoculated with Selected Protease-Assisting Screened B. subtilis YY-4 and L. plantarum 6026, Showed High Availability and Strong Antioxidant and Immunomodulation Potential Capacity.

A study was conducted to investigate the yield of small peptides from rapeseed meal (RSM) by solid-state fermentation (SSF) with acid-protease-assisting B. subtilis YY-4 and L. plantarum CICC6026 (FRSMP). This study explored the availability, antioxidant capacity and immunomodulation activity. The objective of this study was to develop a novel functional food ingredient to contribute to health improvement. The results showed that the concentrations of soluble peptides and free amino acids significantly increased after fermentation (p < 0.001), and the concentration of small molecular peptides (molecular weight < 1 KDa) significantly increased (p < 0.001). The dense surface microstructure of the RSM after fermentation was changed to be loose and porous. The FRSMP exhibited high availability and high antioxidant activity, and it displayed high immunomodulation activity. The novel fermentation was effective for improving the nutritional and biological properties, which provided a feasible method of enhancing the added value.