Grading severity of microscopic vascular invasion was independently associated with recurrence and survival following hepatectomy for solitary hepatocellular carcinoma.

Background: Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, but long-term survival remains unsatisfactory in certain patients. We sought to identify whether the grading severity of microscopic vascular invasion (MVI) was associated with recurrence and survival among patients with solitary HCC. Methods: Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database. Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China: M0 (no MVI), M1 (1-5 sites of MVI occurring ≤1.0 cm away from the tumor), and M2 (>5 sites occurring ≤1.0 cm or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups. Results: Among 227 patients, 97 (42.7%), 83 (36.6%), and 47 (20.7%) patients had M0, M1, and M2, respectively. Median RFS rates among patients with M0, M1, and M2 were 38.3, 35.1, 11.6 months, respectively, while OS rates were 66.8, 62.3, 30.6 months, respectively (both P<0.001). Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS (hazard ratio 1.20, 95% CI: 1.03-1.89, P=0.040; and hazard ratio 1.67, 95% CI: 1.06-2.64, P=0.027) and OS (hazard ratio 1.28, 95% CI: 1.05-2.07, P=0.035; and hazard ratio 1.97, 95% CI: 1.15-3.38, P=0.013). Conclusions: Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC. Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI, especially individuals with more severe MVI grading (M2).

Advances in DNA damage response inhibitors in colorectal cancer therapy.

One potential cause of cancer is genomic instability that arises in normal cells due to years of DNA damage in the body. The clinical application of radiotherapy and cytotoxic drugs to treat cancer is based on the principle of damaging the DNA of cancer cells. However, the benefits of these treatments also have negative effects on normal tissue. While there have been notable advancements in molecular-driven therapy and immunotherapy for colorectal cancer (CRC), a considerable portion of patients with advanced CRC do not experience any benefits from these treatments, leading to a poor prognosis. In recent years, targeted therapy aimed at suppressing the DNA damage response (DDR) in cancer cells has emerged as a potential treatment option for CRC patients, offering them more choices for treatment. Currently, the integration of DDR and clinical intervention remains in the exploratory phase. This review primarily elucidates the fundamental principles of DDR inhibitors, provides an overview of their current clinical application status in CRC, and discusses the advancements as well as limitations observed in relevant studies.

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial.

INTRODUCTION: Neoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer. METHOD AND ANALYSIS: This trial is an open-labelled multicentre prospective randomised controlled trial (NCT05215379) with two parallel groups and allocation ratio 1:1 (nCRT+immunotherapy vs nCRT group). Eligible participants will be aged 18-75 years, with a desire for anus preservation, confirmed cT1-3aN0-1M0 rectal adenocarcinoma, confirmed MSS type, inferior margin of ≤5 cm from the anal verge. The primary endpoint of this trial is complete clinical response (cCR) rate. Immunotherapy is added after 1 week of chemoradiotherapy for two cycles, and then the patients will be administered two cycles of immunotherapy and CAPOX. The evaluations will be carried out after the completion of the whole neoadjuvant therapy. We expect the programme to improve the cCR rate and the quality of life for patients with ultra-low rectal cancer. ETHICS AND DISSEMINATION: This trial was approved by the Ethics committee of Changhai Hospital and other medical centres (Grant number:CHEC2022-118). The results of this study will provide further insight into the clinical efficacy of immunotherapy in combination with nCRT in patients with MSS ultra-low rectal cancer. TRIAL REGISTRATION NUMBER: NCT05215379.

Postoperative infectious complications following laparoscopic versus open hepatectomy for hepatocellular carcinoma: a multicenter propensity score analysis of 3876 patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Single-cell sequencing technology in colorectal cancer: a new technology to disclose the tumor heterogeneity and target precise treatment.

Colorectal Cancer (CRC) is one of the most common gastrointestinal tumors, and its high tumor heterogeneity makes traditional sequencing methods incapable of obtaining information about the heterogeneity of individual cancer cells in CRC. Therefore, single-cell sequencing technology can be applied to better analyze the differences in genetic and protein information between cells, to obtain genomic sequence information of single cells, and to more thoroughly analyze the cellular characteristics and interactions in the CRC microenvironment. This will provide a more comprehensive understanding of colorectal cancer development and metastasis and indicate the treatment plan and prognosis. In this study, we review the application of single-cell sequencing to analyze the tumor microenvironment of CRC, explore the mechanisms involved in CRC metastasis and progression, and provide a reference for potential treatment options.

Lymphatic Contrast-enhanced US to Improve the Diagnosis of Cervical Lymph Node Metastasis from Thyroid Cancer.

Background The presence of cervical lymph node (LN) metastases (LNMs) affects clinical staging and prognosis of thyroid cancer, but the role of conventional B-mode US is limited for preoperative diagnosis of LNMs. The diagnostic value of lymphatic contrast-enhanced US (LCEUS) in thyroid cancer is still being explored. Purpose To explore the diagnostic performance of LCEUS by means of thyroidal injection of contrast agent in comparison with US in detecting LNMs of suspected thyroid cancer. Materials and Methods In this single-center prospective study conducted from November 2020 to January 2021, consecutive participants with suspected thyroid cancer underwent B-mode US and LCEUS of cervical LNs before biopsy. LNMs were confirmed with fine-needle aspiration cytologic examination, thyroglobulin washout assessment, or histopathologic examination after surgery. The diagnostic performance of LCEUS for cervical LNs was compared with that of conventional B-mode US, and its association with LN size and location was evaluated. Results The final data set included 64 participants (mean age, 45 years ± 12 [SD]; 52 women) with 76 LNs. The sensitivity, specificity, and accuracy of LCEUS for LNM were 97%, 90%, and 93%, respectively, whereas they were 81%, 80%, and 80%, respectively, for LNM at conventional B-mode US. Compared with US, LCEUS had better diagnostic accuracy for the LNs smaller than 1 cm (82% vs 95%; P = .03) and for central neck LNs (level VI) (83% vs 96%; P = .04). Conclusion Lymphatic contrast-enhanced US had better diagnostic performance than conventional B-mode US for detecting cervical LN metastases in suspected thyroid cancer before surgery, especially for LNs smaller than 1 cm and central neck LNs. © RSNA, 2023 See also the editorial by Grant and Kwon in this issue.

Aluminum(III)-Based Organic Nanofibrous Gels as an Aggregation-Induced Electrochemiluminescence Emitter Combined with a Rigid Triplex DNA Walker as a Signal Magnifier for Ultrasensitive DNA Assay.

Due to effective tackling of the problems of aggregation-caused quenching of traditional ECL emitters, aggregation-induced electrochemiluminescence (AIECL) has emerged as a research hotspot in aqueous detection and sensing. However, the existing AIECL emitters still encounter the bottlenecks of low ECL efficiency, poor biocompatibility, and high cost. Herein, aluminum(III)-based organic nanofibrous gels (AOGs) are used as a novel AIECL emitter to construct a rapid and ultrasensitive sensing platform for the detection of Flu A virus biomarker DNA (fDNA) with the assistance of a high-speed and hyper-efficient signal magnifier, a rigid triplex DNA walker (T-DNA walker). The proposed AOGs with three-dimensional (3D) nanofiber morphology are assembled in one step within about 15 s by the ligand 2,2':6',2″-terpyridine-4'-carboxylic acid (TPY-COOH) and cheap metal ion Al3+, which demonstrates an efficient ECL response and outstanding biocompatibility. Impressively, on the basis of loop-mediated isothermal amplification-generated hydrogen ions (LAMP-H+), the target-induced pH-responsive rigid T-DNA walker overcomes the limitations of conventional single or duplex DNA walkers in walking trajectory and efficiency due to the entanglement and lodging of leg DNA, exhibiting high stability, controllability, and walking efficiency. Therefore, AOGs with excellent AIECL performance were combined with a CG-C+ T-DNA nanomachine with high walking efficiency and stability, and the proposed "on-off" ECL biosensor displayed a low detection limit down to 23 ag·µL-1 for target fDNA. Also, the strategy provided a useful platform for rapid and sensitive monitoring of biomolecules, considerably broadening its potential applications in luminescent molecular devices, clinical diagnosis, and sensing analysis.

Effect of intradiscal local anesthetic injection on intraoperative pain during percutaneous transforaminal endoscopic discectomy: A retrospective study.

OBJECTIVE: Patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) often complain of unbearable intraoperative pain. This study is to observe clinical effectiveness and safety of intradiscal local anesthetic injection for intraoperative pain relief. METHODS: Total 268 patients who underwent PTED were analyzed. Patients were divided into intradiscal saline injection group (group C) and intradiscal local anesthetic injection group (group L). Intradiscal mixture was consisted of saline or local anesthetic + methylene blue, the amount of injected mixture was 3 mL. Demographic data, visual analog scale (VAS) and Quebec Back Pain Disability Scale (QBPDS) scores, mean arterial pressure (MAP) and heart rate (HR), total dosage of fentanyl, satisfaction rate of anesthesia and complications were collected at different timepoints. RESULTS: Compared with group C (3.94 ± 0.57), there was a significant reduction of VAS in group L (2.83 ± 0.28) during fibrous annular operation phase (T2). Group L had a lower total dosage of fentanyl (71 [63, 78] µg) and a higher anesthesia satisfaction rate (95.3%) than group C (82 [70, 132] µg and 73.6%, respectively) (P < 0.001). MAP and HR were lower in group L than in group C at T2 (P < 0.001). Baseline characteristics and QBPDS scores showed no meaningful intergroup differences. Four cases of complications were reported in this study. CONCLUSION: Intradiscal local anesthetic injection significantly alleviated intraoperative back pain and increased the satisfaction rate of anesthesia, without severe complications, indicating that this technique is a feasible method for intraoperative back pain relief for patients undergoing PTED.

Antimicrobial activity and mechanism of preservatives against Alicyclobacillus acidoterrestris and its application in apple juice.

Alicyclobacillus acidoterrestris has great influence on the quality of apple juice products. In this study, the antibacterial activity of five preservatives (ε-polylysine, propylparaben, monocaprin, octyl gallate and heptylparaben) against A. acidoterrestris and its underlying mechanism were investigated. Results showed that these five preservatives all exerted antibacterial activity through a multiple bactericidal mechanism, and monocaprin and octyl gallate had the highest antibacterial activity, with the minimum inhibitory concentration (MIC) values of 22.5 and 6.25 mg/L, respectively. Five preservatives all changed the permeability of the cell membrane and destroyed the complete cell morphology, with the leakages of the intracellular electrolytes. Moreover, the treatment of ε-polylysine, propylparaben and monocaprin increased the leakage of intracellular protein; propylparaben and octyl gallate reduced the levels of cellular adenosine triphosphate. Also, monocaprin and octyl gallate may stimulate bacteria to release a large amount of reactive oxygen species, so that certain oxidative damage can kill the bacteria. Furthermore, monocaprin and octyl gallate could effectively inactivate the contamination of A. acidoterrestris in apple juices, with the slightly decrease of soluble sugars and organic acids, without significant adverse effects on total sugars and titratable acids. This research highlights the great promise of using monocaprin and octyl gallate as the safe multi-functionalized food additives for food preservations.

Adjuvant immunotherapy improves recurrence-free and overall survival following surgical resection for intermediate/advanced hepatocellular carcinoma a multicenter propensity matching analysis.

Background & aims: The effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC. Methods: Using a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS. Results: Among the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC. Conclusion: This real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

[CircRNA-0028171 regulates arsenic trioxide-induced apoptosis in vascular endothelial cells].

The present study was aimed to investigate the effects of circRNA-0028171 on the apoptosis of vascular endothelial cells induced by arsenic trioxide (As2O3). Human umbilical vein endothelial cells (HUVECs) were treated with 0-15 µmol/L As2O3 for 24 h. Then, cellular viability was measured by MTT assay. The expression levels of circRNA-0028171, Bcl-2 and Bax mRNA were detected by real-time quantitative PCR. Bcl-2/Bax protein ratio was detected by Western blot. Whether circRNA-0028171 was involved in the regulation of HUVECs by As2O3 was investigated by transfection with overexpression plasmid of circRNA-0028171 and siRNA. The results showed that compared with the control group, As2O3 group showed decreased cellular viability, reduced Bcl-2/Bax mRNA and protein ratios, and significantly lower expression of circRNA-0028171. Overexpression of circRNA-0028171 inhibited apoptosis of HUVECs induced by As2O3. Knockdown of circRNA-0028171 by siRNA promoted As2O3-induced apoptosis in HUVECs. These results suggest that circRNA-0028171 is involved in the vascular endothelial cell apoptosis induced by As2O3.

Highly Enhancing the Interfacial and Mechanical Properties of Basalt Fiber/Poly(phthalazinone ether nitrile ketone) Composite by Thermoplastic Sizing Agents with Different Structures.

The interfacial modification of basalt-fiber-reinforced polymer (BFRP) composites is an essential research field and many techniques have been developed to improve the adhesion between basalt fiber (BF) and the matrix. However, most studies were based on the matrixes of general plastics and epoxy resins. In this work, five different chain structures of thermoplastic sizing agents were used to improve the interfacial properties of unidirectional BF-reinforced soluble and high-temperature-resistant poly(phthalazinone ether nitrile ketone) (BF/PPENK) composites. DMA results showed that the poly(ether nitrile) (PEN)-sized BF/PPENK (BF-PEN/PPENK) composite exhibited the optimal interfacial performance, with a storage modulus (E') and glass transition temperature (Tg) up to 50 GPa and 288 °C, respectively. Moreover, the tensile strength, compressive strength, flexural strength, and interlaminar shear strength of the BF-PEN/PPENK composite reached 778 MPa, 600 MPa, 1115 MPa and 57 MPa, respectively, and increased by 42%, 49%, 20% and 30% compared with the desized BF/PPENK composite. This study provides some suggestions for the design of sizing agents to modify the interface of BF and high-performance thermoplastic resin.

Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer.

Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross-linked nanocomposite hydrogel, the click reaction improves drug-release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.

Lactobacillus kefiranofaciens JKSP109 and Saccharomyces cerevisiae JKSP39 isolated from Tibetan kefir grain co-alleviated AOM/DSS induced inflammation and colorectal carcinogenesis.

This study aimed to investigate the alleviative effects of Lactobacillus kefiranofaciens JKSP109 (LK) and Saccharomyces cerevisiae JKSP39 (SC) isolated from Tibetan kefir grain on colon inflammation and colorectal carcinogenesis. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to establish a mouse model of colorectal cancer (CRC). The treatment group mice were administered with LK, SC, or the combination of LK and SC for five days per week from the day of receiving AOM. The composition of the gut microbiota was assessed using internal transcribed spacer 2 and 16S rRNA gene high-throughput sequencing. Furthermore, the biomarkers associated with gut barrier integrity, inflammation, regulators of cell proliferation, and apoptosis were evaluated. The results showed that the administration of LK, SC, and their combination increased the body weights and decreased the disease activity index (DAI) score and tumor multiplicity. As compared to the CRC model group, the three treatment groups positively regulated the gut microbiota. Meanwhile, the three treatments also enhanced the gut barrier, decreased the expression of proinflammatory cytokines and oncocyte proliferation indicators, and increased the expression of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive tumor epithelial cells and content of short chain fatty acids in fecal samples. All these results indicated that the LK and SC alleviated the inflammation and colorectal carcinogenesis in AOM/DSS-induced CRC mouse models, and the majority of tested indexes in the combination group were superior to single strain groups.

[Comparison between Ultrasonography and CT in Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma].

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ2=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ 2=82.26,P<0.001;χ2=114.01,P<0.001;χ2=82.26,P<0.001) and accuracy (χ2=20.27,P<0.001;χ2=15.56,P<0.001;χ2=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ2=17.01,P<0.001;χ2=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.

Fabrication of Epsilon-Polylysine-Based Magnetic Nanoflowers with Effective Antibacterial Activity against Alicyclobacillus acidoterrestris.

The risk of fruit juice contamination caused by microorganisms, especially Alicyclobacillus acidoterrestris, has been reported worldwide. To develop cost-effective control methods, in this work, flower-like magnetic molybdenum disulfide (Fe3O4@MoS2) nanoparticles (NPs) were fabricated by a facile two-step hydrothermal method. After further modifying polyacrylic acid (PAA) on the surface of the NPs, epsilon-polylysine (EPL) was immobilized via N-(3-dimethylaminopropyl)-N-carbodiimide hydrochloride/N-hydroxysuccinimide coupling reaction to obtain the Fe3O4@MoS2@PAA-EPL nanocomposites. Antibacterial results exhibited that the synthesized nanocomposites showed effective antibacterial activity against A. acidoterrestris with a minimum inhibitory concentration of 0.31 mg mL-1. Investigation on the antibacterial mechanism revealed that the presence of nanocomposites caused damage and disruption of the bacterial membrane through dent formation, resulting in the leakage of intracellular protein. Moreover, the activity of dehydrogenase enzymes was inhibited with the treatment of Fe3O4@MoS2@PAA-EPL, causing the reduction of metabolic activity and adenosine triphosphate levels in bacteria. Simultaneously, the presence of nanocomposites improved intracellular reactive oxygen species levels, and this disrupted the antioxidant defense system and caused oxidative damage to bacteria. Furthermore, Fe3O4@MoS2@PAA-EPL nanocomposites were confirmed to possess satisfactory biocompatibility by performing in vitro cytotoxicity and in vivo acute toxicity experiments. The aim of this research was to develop a new pathway for the inhibition of A. acidoterrestris in the juice industry.

Supplementation of kefir ameliorates azoxymethane/dextran sulfate sodium induced colorectal cancer by modulating the gut microbiota.

The aim of this study was to investigate the efficacy of kefir on colorectal cancer (CRC) via regulating the microbiota structure in the colon using the azoxymethane/dextran sulfate sodium (AOM/DSS) induced CRC mouse model. Mice in the treatment group were orally administered with milk or kefir. The gut microbiota composition was assessed by internally transcribed spacer 2 (ITS2) and 16S rRNA high-throughput sequencing. Furthermore, the biomarkers associated with the gut barrier, inflammation, and cell proliferation regulators were evaluated. The results indicated that the size and the amount of tumor were decreased and the immunity regulators (TNF-α, IL-6, and IL-17a) and oncocyte proliferation indicator (Ki67, NF-κB, and ß-catenin) were all decreased. Increased short chain fatty acids (SCFAs) lowered the pH in the colon and helped enhance the intestinal barrier. The Firmicutes/Bacteroidetes ratio and Ascomycota/Basidiomycota ratio were decreased at the phylum level; the relative abundance of probiotics was increased and the pathogenic bacterium (Clostridium sensu stricto, Aspergillus and Talaromyces) were decreased after supplementation of kefir. Consequently, kefir could regulate the gut microbiota composition and ameliorate AOM/DSS induced colorectal cancer.

Biointerfacing Antagonizing T-Cell Inhibitory Nanoparticles Potentiate Hepatocellular Carcinoma Checkpoint Blockade Therapy.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with few effective treatment options all around the world. The efficacy of the arisen immune checkpoint therapy is still uncertain due to local immunosuppression. In order to further overcome T cell suppression in the tumor immune microenvironment while promoting the immune response of antigen-presenting cells, a biointerfacing antagonizing T-cell inhibitory nanoparticles (BAT NPs) has been developed by cloaking platelet membrane on the PLGA microsphere surface to load T-cell immunoglobulin domain and mucin domain-3 antibodies (anti-TIM-3) as well as PD-L1. Notably, in addition to activating the proliferation and migration of T cells, the contained anti-TIM-3 can cooperate with PD-L1 checkpoint blockade to exert therapeutic effects. Furthermore, the components of BAT NPs like anti-TIM-3 and platelet can act together for collagen deposition in tumor starvation treatment. Thus, a novel targeting therapeutic strategy that can effectively reverse the immune-inhibiting microenvironment is effectively applied to PD-L1 checkpoint combination therapy. Such therapeutic effect can subsequently activate the effector T lymphocytes and antigen presentation of dendritic cells as well as the polarization of M1-type macrophages. Last, the study presented the synergistic effect of immune therapeutic adjuvants and BAT NPs components in achieving tumor inhibition and prolonging tumor-burden survival.