Determination of adulteration, geographical origins, and species of food by mass spectrometry.

Food adulteration, mislabeling, and fraud, are rising global issues. Therefore, a number of precise and reliable analytical instruments and approaches have been proposed to ensure the authenticity and accurate labeling of food and food products by confirming that the constituents of foodstuffs are of the kind and quality claimed by the seller and manufacturer. Traditional techniques (e.g., genomics-based methods) are still in use; however, emerging approaches like mass spectrometry (MS)-based technologies are being actively developed to supplement or supersede current methods for authentication of a variety of food commodities and products. This review provides a critical assessment of recent advances in food authentication, including MS-based metabolomics, proteomics and other approaches.

Ensemble Transductive Propagation Network for Semi-Supervised Few-Shot Learning.

Few-shot learning aims to solve the difficulty in obtaining training samples, leading to high variance, high bias, and over-fitting. Recently, graph-based transductive few-shot learning approaches supplement the deficiency of label information via unlabeled data to make a joint prediction, which has become a new research hotspot. Therefore, in this paper, we propose a novel ensemble semi-supervised few-shot learning strategy via transductive network and Dempster-Shafer (D-S) evidence fusion, named ensemble transductive propagation networks (ETPN). First, we present homogeneity and heterogeneity ensemble transductive propagation networks to better use the unlabeled data, which introduce a preset weight coefficient and provide the process of iterative inferences during transductive propagation learning. Then, we combine the information entropy to improve the D-S evidence fusion method, which improves the stability of multi-model results fusion from the pre-processing of the evidence source. Third, we combine the L2 norm to improve an ensemble pruning approach to select individual learners with higher accuracy to participate in the integration of the few-shot model results. Moreover, interference sets are introduced to semi-supervised training to improve the anti-disturbance ability of the mode. Eventually, experiments indicate that the proposed approaches outperform the state-of-the-art few-shot model. The best accuracy of ETPN increases by 0.3% and 0.28% in the 5-way 5-shot, and by 3.43% and 7.6% in the 5-way 1-shot on miniImagNet and tieredImageNet, respectively.

Evaluation of Federated Learning in Phishing Email Detection.

The use of artificial intelligence (AI) to detect phishing emails is primarily dependent on large-scale centralized datasets, which has opened it up to a myriad of privacy, trust, and legal issues. Moreover, organizations have been loath to share emails, given the risk of leaking commercially sensitive information. Consequently, it has been difficult to obtain sufficient emails to train a global AI model efficiently. Accordingly, privacy-preserving distributed and collaborative machine learning, particularly federated learning (FL), is a desideratum. As it is already prevalent in the healthcare sector, questions remain regarding the effectiveness and efficacy of FL-based phishing detection within the context of multi-organization collaborations. To the best of our knowledge, the work herein was the first to investigate the use of FL in phishing email detection. This study focused on building upon a deep neural network model, particularly recurrent convolutional neural network (RNN) and bidirectional encoder representations from transformers (BERT), for phishing email detection. We analyzed the FL-entangled learning performance in various settings, including (i) a balanced and asymmetrical data distribution among organizations and (ii) scalability. Our results corroborated the comparable performance statistics of FL in phishing email detection to centralized learning for balanced datasets and low organizational counts. Moreover, we observed a variation in performance when increasing the organizational counts. For a fixed total email dataset, the global RNN-based model had a 1.8% accuracy decrease when the organizational counts were increased from 2 to 10. In contrast, BERT accuracy increased by 0.6% when increasing organizational counts from 2 to 5. However, if we increased the overall email dataset by introducing new organizations in the FL framework, the organizational level performance improved by achieving a faster convergence speed. In addition, FL suffered in its overall global model performance due to highly unstable outputs if the email dataset distribution was highly asymmetric.

Duodenal microbiota makes an important impact in functional dyspepsia.

Duodenal microbiota may have impact in Functional Dyspepsia. The aim of this study was to explore the difference of microbiota on duodenal mucosa between patients with Functional Dyspepsia and normal subjects. The duodenal mucosa of the subjects were collected under upper gastrointestinal endoscope and the contents of the descending duodenal intestine were extracted with cell brushes in 20 patients with Functional Dyspepsia and 5 healthy subjects. The microbiome on duodenal was studied by 16SrDNA gene sequencing. The differences of duodenal flora were analyzed and compared by LEfSe, FAPROTAX, SPSS and other software. There were significant differences in ACE index, shannon index and observedspecies index between patients with functional dyspepsia and healthy people (P < 0.05). PCoA analysis of the structure of bacteria between two groups found that the duodenal microbiome showed a separate trend. In further study, Amova analysis showed a significant difference (P < 0.05). We found that the there are obvious differences in the composition of duodenal microbiome in functional dyspepsia and healthy people. At the genus level, there were significant differences in Alloprevotella, Peptostreptococcus,Sutterella, Corynebacteriurn,Catonella, Faecalibacterium,Staphylococcus,Eubacteriumnodatumgro-up, Lachnoclostridiurn and Lautropia between the two groups (P < 0.05). The prediction results of Microflora function from FAPROTAX showed that the urea decomposing (ureolysis) and fumaric acid respiratory (fumaraterespiration) function of duodenal bacteria in patients with functional dyspepsia were significantly different from those in healthy people (P < 0.05). In conclusion, there is a significant difference in mucosal microflora of duodenum between patients with functional dyspepsia and healthy groups. It includes greater microflora diversity, different microflora structure, different microflora composition, specific taxa and specific microbiome function. The disorder of duodenal microecology may be the formation mechanism of functional dyspepsia.

Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients.

Depression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.

Aiduqing formula inhibits breast cancer metastasis by suppressing TAM/CXCL1-induced Treg differentiation and infiltration.

BACKGROUND: Metastasis represents the leading cause of death in patients with breast cancer. Traditional Chinese medicine is particularly appreciated for metastatic diseases in Asian countries due to its benefits for survival period prolongation and immune balance modulation. However, the underlying molecular mechanisms remain largely unknown. This study aimed to explore the antimetastatic effect and immunomodulatory function of a clinical formula Aiduqing (ADQ). METHODS: Naive CD4+ T cells, regulatory T cells (Tregs), and CD8+ T cells were sorted by flow cytometry. Then, breast cancer cells and these immune cells were co-cultured in vitro or co-injected into mice in vivo to simulate their coexistence. Flow cytometry, ELISA, qPCR, double luciferase reporter gene assay, and chromatin immunoprecipitation assay were conducted to investigate the immunomodulatory and antimetastatic mechanisms of ADQ. RESULTS: ADQ treatment by oral gavage significantly suppressed 4T1-Luc xenograft growth and lung metastasis in the orthotopic breast cancer mouse model, without noticeable hepatotoxicity, nephrotoxicity, or hematotoxicity. Meanwhile, ADQ remodeled the immunosuppressive tumor microenvironment (TME) by increasing the infiltration of tumor-infiltrating lymphocytes (TILs) and cytotoxic CD8+ T cells, and decreasing the infiltration of Tregs, naive CD4+ T cells, and tumor-associated macrophages (TAMs). Molecular mechanism studies revealed that ADQ remarkably inhibited CXCL1 expression and secretion from TAMs and thus suppressed the chemotaxis and differentiation of naive CD4+ T cells into Tregs, leading to the enhanced cytotoxic effects of CD8+ T cells. Mechanistically, TAM-derived CXCL1 promoted the differentiation of naive CD4+ T cells into Tregs by transcriptionally activating the NF-κB/FOXP3 signaling. Lastly, mouse 4T1-Luc xenograft experiments validated that ADQ formula inhibited breast cancer immune escape and lung metastasis by suppressing the TAM/CXCL1/Treg pathway. CONCLUSIONS: This study not only provides preclinical evidence supporting the application of ADQ in inhibiting breast cancer metastasis but also sheds novel insights into TAM/CXCL1/NF-κB/FOXP3 signaling as a promising therapeutic target for Treg modulation and breast cancer immunotherapy. Video Abstract.

Glochidion littorale Leaf Extract Exhibits Neuroprotective Effects in Caenorhabditis elegans via DAF-16 Activation.

A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans. GLE treatment ameliorated H2O2-induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson's syndrome.

Fucoidan exerts antidepressant-like effects in mice via regulating the stability of surface AMPARs.

The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown seaweeds with anti-inflammatory activity. However, the antidepressant effects of fucoidan on chronic stress-induced depressive-like behaviors have not been well elucidated. Here, we used two different depressive-like mouse models, lipopolysaccharide (LPS) and chronic restraint stress (CRS) models, to explore the detailed molecular mechanism underlying its antidepressant-like effects in C57BL/6J mice by combining multiple behavioral, molecular and immunofluorescence experiments. Adenovirus-mediated overexpression of caspase-1 and pharmacological inhibitors were also used to clarify the antidepressant mechanisms of fucoidan. We found that acute administration of fucoidan did not produce antidepressant effects in the tail suspension test (TST) and forced swim test (FST). Interestingly, chronic fucoidan administration not only dose-dependently reduced stress-induced depressive-like behaviors in the TST, FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT), but also alleviated the downregulation of brain-derived neurotrophic factor (BDNF)-dependent synaptic plasticity via inhibiting caspase-1-mediated inflammation in the hippocampus of mice. Moreover, fucoidan significantly ameliorated behavioral and synaptic plasticity abnormalities in the overexpression of caspase-1 in the hippocampus of mice. Furthermore, blocking BDNF abolished the antidepressant-like effects of fucoidan in mice. Therefore, our findings clearly indicate that fucoidan provides a potential supplementary noninvasive treatment for depression by inhibition of hippocampal inflammation.

CLDN4 silencing promotes proliferation and reduces chemotherapy sensitivity of gastric cancer cells through activation of the PI3K/Akt signalling pathway.

NEW FINDINGS: What is the central question of this study? What is the influence of the interaction between the matrix protein CLDN4 and the PI3K/Akt signalling pathway on tumour progression and chemotherapy sensitivity in gastric cancer? What is the main finding and its importance? Silencing of CLDN4 can promote the growth and proliferation of gastric cancer cells by activating the PI3K/Akt signalling pathway, and thus reduce the sensitivity of gastric cancer cells to chemotherapy. ABSTRACT: Gastric cancer (GC) is one of the most common cancers worldwide and has a high mortality rate, accompanied by metastasis. Claudins (CLDNs) are major tight-junction proteins that mediate cellular polarity and differentiation. In the present study, we investigated the role of claudin 4 (CLDN4) in modulating cell proliferation and chemotherapeutic sensitivity in GC. Immunohistochemistry and RT-qPCR were initially used to detect the expression of CLDN4 in cancer tissues and adjacent normal tissues collected from GC patients. GC cell lines with the highest and the lowest CLDN4 expression were selected for subsequent experiments. The effects of CLDN4 on GC cell chemosensitivity, proliferation, invasion, migration, apoptosis and tumourigenic capacity were evaluated by conducting gain- and loss-of-function studies of CLDN4. Expression of CLDN4 was significantly decreased in GC tissues and cell lines compared to adjacent normal tissues or gastric epithelial cells. Silencing of CLDN4 increased the extent of PI3K and Akt phosphorylation, and also the proliferation, migration, invasion and tumourigenesis of GC cells; at the same time apoptosis and the sensitivity of GC cells to chemotherapy were reduced. In conclusion, CLDN4 may play a pivotal role in attenuating GC cell proliferation and enhancing sensitivity of GC cells to chemotherapy by inactivating the PI3K/Akt signalling pathway.

XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling.

BACKGROUND: Recent findings suggested that premetastatic niche (PMN) is a prerequisite in mediating cancer metastasis. Previously we demonstrated that XIAOPI formula could inhibit breast cancer lung metastasis via inhibiting tumor associated macrophages (TAMs)-secreted CXCL1. Herein, we aimed to explore the effects of XIAOPI formula on preventing breast cancer PMN formation and its underlying molecular mechanisms. METHODS: CXCL1 expression of TAMs was detected by qPCR and Western blotting assay. The influences of XIAOPI formula on the proliferation of TAMs and 4 T1 in the co-culture system were tested by CCK8 or EdU staining. Transwell experiment was applied to determine the effects of XIAOPI formula on the invasion ability of HSPCs and 4 T1. Breast cancer xenografts were built by inoculating 4 T1 cells into the mammary pads of Balb/c mice and lung metastasis was monitored by luciferase imaging. Immune fluorescence assay was used to test the epithelial-mesenchymal transition process and PMN formation in the lung tissues. The effects of XIAOPI formula on TAMs phenotype, hematopoietic stem/progenitor cells (HSPCs) and myeloid-derived suppressor cells (MDSCs) were determined by flow cytometry. RESULTS: It was found that XIAOPI formula could inhibit the proliferation and polarization of M2 phenotype macrophages, and reduce CXCL1 expression in a dose-dependent manner. However, M1 phenotype macrophages were not significantly affected by XIAOPI formula. TAMs/CXCL1 signaling was subsequently found to stimulate the recruitment of c-Kit+/Sca-1+ HSPCs and their differentiation into CD11b+/Gr-1+ MDSCs, which were symbolic events accounting for PMN formation. Moreover, XIAOPI formula was effective in inhibiting HSPCs activation and suppressing the proliferation and metastasis of breast cancer cells 4 T1 induced by HSPCs and TAMs co-culture system, implying that XIAOPI was effective in preventing PMN formation in vitro. Breast cancer xenograft experiments further demonstrated that XIAOPI formula could inhibit breast cancer PMN formation and subsequent lung metastasis in vivo. The populations of HSPCs in the bone marrow and MDSCs in the lung tissues were all remarkably declined by XIAOPI formula treatment. However, the inhibitory effects of XIAOPI formula could be relieved by CXCL1 overexpression in the TAMs. CONCLUSIONS: Taken together, our study provided preclinical evidence supporting the application of XIAOPI formula in preventing breast cancer PMN formation, and highlighted TAMs/CXCL1 as a potential therapeutic strategy for PMN targeting therapy. Video Abstract.

Proteomic analysis of "Oriental Beauty" oolong tea leaves with different degrees of leafhopper infestation.

RATIONALE: Oriental Beauty, a type of oolong tea native to Taiwan, is highly prized by connoisseurs for its unique fruity aroma and sweet taste. Leaves of Oriental Beauty vary in appearance, aroma, and taste, depending on the degree of tea green leafhopper (Jacobiasca formosana) infestation. In this study, the aim is to investigate the differential expression of proteins in leaves with low, medium, and high degrees of leafhopper infestation. METHODS: Proteomic techniques 2DE (two-dimensional electrophoresis) and nanoscale liquid chromatography/tandem mass spectrometry (LC/MS/MS) were used to investigate the differential expression of proteins in tea leaves with different degrees of leafhopper infestation. RESULTS: A total of 89 proteins were found to exhibit significant differences in expression. In a gene ontology analysis, most of these proteins participated in biosynthesis, carbohydrate metabolism, transport, responses to stress, and amino acid metabolism. CONCLUSIONS: These results indicated that the unique aroma and taste of the leaves might be influenced by their protein expression profiles, as well as related factors such as defensive responses to tea green leafhopper saliva.

The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS: A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). CONCLUSIONS: This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.

Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin-1-targeting oxidant damage.

Accumulating evidence suggests that caveolin-1 (CAV-1) is a stress-related oncotarget and closely correlated to chemoresistance. Targeting CAV-1 might be a promising strategy to improve chemosensitivity for breast cancer treatment. Astragaloside IV (AS-IV), a bioactive compound purified from Astragalus membranaceus, has been shown to exhibit multiple bioactivities, including anticancer. However, the involved molecular targets are still ambiguous. In this study, we investigated the critical role of CAV-1 in mediating the chemosensitizing effects of AS-IV to Taxol on breast cancer. We found that AS-IV could enhance the chemosensitivity of Taxol with minimal direct cytotoxicity on breast cancer cell lines MCF-7 and MDA-MB-231, as well as the nontumor mammary epithelial cell line MCF-10A. AS-IV was further demonstrated to aggravate Taxol-induced apoptosis and G2/M checkpoint arrest. The phosphorylation of mitogen-activated protein kinase (MAPK) signaling extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK), except p38, was also abrogated by a synergistic interaction between AS-IV and Taxol. Moreover, AS-IV inhibited CAV-1 expression in a dose-dependent manner and reversed CAV-1 upregulation induced by Taxol administration. Mechanism study further demonstrated that AS-IV treatment triggered the eNOS/NO/ONOO- pathway via inhibiting CAV-1, which led to intense oxidant damage. CAV-1 overexpression abolished the chemosensitizing effects of AS-IV to Taxol by inhibiting oxidative stress. In vivo experiments further validated that AS-IV increased Taxol chemosensitivity on breast cancer via inhibiting CAV-1 expression, followed by activation of the eNOS/NO/ONOO- pathway. Taken together, our findings not only suggested the potential of AS-IV as a promising candidate to enhance chemosensitivity, but also highlighted the significance of CAV-1 as the target to reverse cancer drug resistance.

Overexpression of microRNA-98 inhibits cell proliferation and promotes cell apoptosis via claudin-1 in human colorectal carcinoma.

Colorectal carcinoma (CRC) is a major cause of cancer-related deaths worldwide, and investigations on novel targets are imperative. MiR-98 has been reported to act as a tumor suppressor in several cancers. To evaluate miR-98 as a novel anticancer molecule for CRC, examinations to validate whether miR-98 conferred an inhibiting effect on proliferation, migration, and invasion were performed. The microarray-based gene expression profiling involving CRC was used to identify the differentially expressed genes. The potential relationship between miR-98 and CLDN1 was analyzed by cell experimentation. Then, the CRC cells were transfected with miR-98 mimic or miR-98 inhibitor to investigate the potential effect of miR-98 overexpression and depletion on CRC cell proliferation, migration, invasion, and apoptosis. The expressions of CLDN1, Bcl-2 associated protein x (Bax), runt-related transcription factor 3 (RUNX3), B-cell lymphoma 2 (Bcl-2), C-myc, and proliferating cell nuclear antigen (PCNA) were determined. The downregulated miR-98 along with an upregulated CLDN1 was observed in CRC, in which miR-98 could target to regulate CLDN1. The overexpression of miR-98 or silencing of CLDN1 was shown to increase the expression of Bax and RUNX3 along with promoted cell apoptosis and arrested cells in G1 phase, while decreasing the expression of CLDN1, Bcl-2, C-myc, and PCNA with suppressed proliferation, migration, and invasion. Collectively, the current study supports the notion that miR-98 plays an inhibitory role in human CRC cell proliferation, migration, and invasion and act as a contributor for cell apoptosis by downregulating CLDN1. The current study highlights a potential future strategy to help prevent the development of CRC.

Impact of continuous positive airway pressure on vascular endothelial growth factor in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Cumulative evidence supports the clear relationship of obstructive sleep apnea (OSA) with cardiovascular disease (CVD). And, adherence to continuous positive airway pressure (CPAP) treatment alleviates the risk of CVD in subjects with OSA. Vascular endothelial growth factor (VEGF), a potent angiogenic cytokine regulated by hypoxia-inducible factor, stimulates the progression of CVD. Thus, whether treatment with CPAP can actually decrease VEGF in patients with OSA remains inconclusive. The purpose of the present study was to quantitatively evaluate the impact of CPAP therapy on VEGF levels in OSA patients. METHODS: We systematically searched Web of Science, Cochrane Library, PubMed, and Embase databases that examined the impact of CPAP on VEGF levels in OSA patients prior to May 1, 2017. Related searching terms were "sleep apnea, obstructive," "sleep disordered breathing," "continuous positive airway pressure," "positive airway pressure," and "vascular endothelial growth factor." We used standardized mean difference (SMD) to analyze the summary estimates for CPAP therapy. RESULTS: Six studies involving 392 patients were eligible for the meta-analysis. Meta-analysis of the pooled effect showed that levels of VEGF were significantly decreased in patients with OSA before and after CPAP treatment (SMD = - 0.440, 95% confidence interval (CI) = - 0.684 to - 0.196, z = 3.53, p = 0.000). Further, results demonstrated that differences in age, body mass index, apnea-hypopnea index, CPAP therapy duration, sample size, and racial differences also affected CPAP efficacy. CONCLUSIONS: Improved endothelial function measured by VEGF may be associated with CPAP therapy in OSA patients. The use of VEGF levels may be clinically important in evaluating CVD for OSA patients. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.

Cleavable Multifunctional Targeting Mixed Micelles with Sequential pH-Triggered TAT Peptide Activation for Improved Antihepatocellular Carcinoma Efficacy.

Although tumor-targeting nanovehicles for hepatocellular carcinoma (HCC) chemotherapy have attracted great research and clinic interest, the poor cancer penetration, inefficient cellular uptake, and slow intracellular drug release greatly compromise their therapeutic outcomes. In this work, a multifunctional mixed micellar system, consisting of glycyrrhetinic acid (GA) for specific liver-targeting, trans-activator of transcription (TAT) peptide for potent cell penetration, and pH-sensitive poly(ß-amino ester) polymers for acidic-triggered drug release, was developed to provide HCC-targeting delivery and pH-triggered release of doxorubicin (DOX). These micelles were hypothesized to efficaciously accumulate in HCC site by the guide of GA ligands, enter into cancer cells facilitated by the activated TAT peptide on the micellar surface, and finally rapidly release DOX in cytoplasm. To demonstrate this design, DOX was initially loaded in micelles modified with both GA and TAT (DOX/GA@TAT-M) with high drug loading efficiency and pH-sensitive drug release profiles. The HCC-targeting cellular uptake and synergetic anticancer efficacy were tested, indicating DOX/GA@TAT-M could be specifically and effectively internalized into HCC cells by the effect of GA targeting and TAT penetrating with enhanced cytotoxicity. In addition, the prolonged circulation time and enhanced accumulation in tumor facilitated its potent tumor growth inhibition activity in vivo. These results demonstrated that the cleavable multifunctional mixed micelles with tumor targeting, controlled TAT peptide activation, and sequential pH-sensitive drug release could be an efficient strategy for HCC treatment.

Selective antibacterial activity of patchouli alcohol against Helicobacter pylori based on inhibition of urease.

The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H.pylori and jack bean in concentration-dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver-Burk plots indicated that the type of inhibition was non-competitive against H.pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA-inactivated urease assay showed DL-dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H.pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H.pylori infection.

Successful Undergoing Esophagogastric Anastomosis with Right Gastroepiploic Vessels Congenital Absence: A Case Report.

A 60-year-old male farmer was admitted to the hospital with dysphagia for 2 months, and minimally invasive McKeown esophagectomy with lymphadenectomy was initially planned. However, congenital absence of the right gastroepiploic vessels (RGEVs) was blocked surgical procedure. Fortunately, we successfully performed esophagectomy and unconventional gastric remnant reconstruction without RGEVs, and intraoperative cervical venous superdrainage.

Metabolomics reveals the potential metabolic mechanism of infliximab against DSS-induced acute and chronic ulcerative colitis.

Inflammatory bowel disease (IBD) is often accompanied by metabolic imbalance, and infliximab (IFX) can alleviate IBD symptoms, but its metabolic mechanisms remain unclear. To investigate the relationship between IBD, metabolism, and IFX, an acute and chronic ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) was established. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis. The results showed that IFX could alleviate colonic shortening and reduce colonic pathological damage in acute and chronic mouse colitis, improve acute and chronic UC, and ameliorate metabolic disturbances. Among the 104 elevated metabolites and 170 decreased metabolites, these metabolites mainly belonged to amino acids, glucose, and purines. The changes in these metabolites were mainly associated with drug metabolism-other enzymes, riboflavin metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phosphonate and phosphinate metabolism, and phenylalanine metabolism. In summary, this study provides a valuable approach to explore the metabolic mechanisms of IFX in treating acute and chronic UC from a metabolomics perspective.