Cytotoxic indole diterpenoids and rare pyridoxatin atropisomers from the endophytic fungus Tolypocladium sp. SHJJ1.

Phytochemical investigation on the extract of endophytic fungus Tolypocladium sp. SHJJ1 resulted in the identification of a pair of previously undescribed pyridoxatin atropisomers [1 (M/P)] and three new indole diterpenoids (3-5), together with a pair of known pyridoxatin atropisomers [2 (M/P)] and ten known indole diterpenoids (6-15). Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Among the undescribed natural products, [1 (M/P)] that two rapidly interconverting atropisomers are the third example to report in the pyridoxatin atropisomers. Except for compounds 1 (M/P) and 2 (M/P), all other compounds were tested for their cytotoxicity using HepG2, A549, and MCF-7 human cell lines. Compound 9 displayed moderate cytotoxicity against the HepG2, A549, and MCF-7 cell lines with IC50 values of 32.39 ± 1.48 µM, 26.06 ± 1.14 µM, and 31.44 ± 1.94 µM, respectively, which was similar to the positive drug cisplatin (with IC50 values of 32.55 ± 1.76 µM, 18.40 ± 1.43 µM, and 27.31 ± 1.22 µM, respectively).

[Machine learning algorithms for identifying autism spectrum disorder through eye-tracking in different intention videos]. / ä¸åŒæ„å›¾åœºæ™¯çœ¼åŠ¨æ³¨è§†æ¨¡å¼æœºå™¨å­¦ä¹ ç®—æ³•è¯†åˆ«å­¤ç‹¬ç—‡è°±ç³»éšœç¢çš„ç ”ç©¶.

OBJECTIVES: To investigate the differences in visual perception between children with autism spectrum disorder (ASD) and typically developing (TD) children when watching different intention videos, and to explore the feasibility of machine learning algorithms in objectively distinguishing between ASD children and TD children. METHODS: A total of 58 children with ASD and 50 TD children were enrolled and were asked to watch the videos containing joint intention and non-joint intention, and the gaze duration and frequency in different areas of interest were used as original indicators to construct classifier-based models. The models were evaluated in terms of the indicators such as accuracy, sensitivity, and specificity. RESULTS: When using eight common classifiers, including support vector machine, linear discriminant analysis, decision tree, random forest, and K-nearest neighbors (with K values of 1, 3, 5, and 7), based on the original feature indicators, the highest classification accuracy achieved was 81.90%. A feature reconstruction approach with a decision tree classifier was used to further improve the accuracy of classification, and then the model showed the accuracy of 91.43%, the specificity of 89.80%, and the sensitivity of 92.86%, with an area under the receiver operating characteristic curve of 0.909 (P<0.001). CONCLUSIONS: The machine learning model based on eye-tracking data can accurately distinguish ASD children from TD children, which provides a scientific basis for developing rapid and objective ASD screening tools.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner.

Objective: To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC). Methods: The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay. Results: The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells. Conclusion: Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Dietary supplementation of water extract of Eucommia ulmoides bark improved caecal microbiota and parameters of health in white-feathered broilers.

Eucommia ulmoides has been used as a food and medicine homologue for a long time in China. We hypothesize that Eucommia ulmoides achieves its health-promoting effects via altering gut microbiota. Here, we investigated the effects of water extract of Eucommia ulmoides bark on caecal microbiota and growth performance, antioxidant activity, and immunity in white-feathered broilers treated for 42 days. A total of 108 one-day-old Cobb white-feathered broilers were randomly assigned to three treatment groups: control diet, 0.75% Eucommia ulmoides diet (EU Ⅰ) and 1.5% Eucommia ulmoides diet (EU Ⅱ). The results showed that EU Ⅱ treatment improved average body weight (ABW), thigh muscle quality and total length of intestines, and decreased the serum total triglycerides and total cholesterol (TC) (p < 0.05). Eucommia ulmoides supplementation increased serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant activities and content of immunoglobulins, and reduced levels of malondialdehyde and tumour necrosis factor-α (TNF-α) (p < 0.05). Moreover, the supplementation increased the diversity of caecal microbiota and reduced the pathogenic genera Escherichia Shigella and Helicobacter. The genera Ochrobactrum, Odoribater, Klebsiella, Enterobacter, Georgenia and Bifidobacterium were positively associated with the ABW, total intestinal length, serum levels of GSH-Px, SOD and immunoglobulins (p < 0.001) and negatively associated with the TC and TNF-α (p < 0.01), suggesting an association of the changes of gut microbiota and improvement of broiler health. Meanwhile, Eucommia ulmoides supplementation enriched the Kyoto Encyclopedia of Genes and Genomes pathway of exocrine secretion from the pancreas, circadian entrainment and inhibited lipopolysaccharide biosynthesis. In conclusion, Eucommia ulmoides water extract can be used as a feed additive to improve poultry industry production.

[Differential diagnosis of autism spectrum disorder and global developmental delay based on machine learning and Children Neuropsychological and Behavioral Scale]. / åŸºäºŽæœºå™¨å­¦ä¹ å’Œå„¿ç«¥ç¥žç»å¿ƒç†è¡Œä¸ºæ£€æŸ¥é‡è¡¨é‰´åˆ«å­¤ç‹¬ç—‡è°±ç³»éšœç¢å’Œå ¨é¢å‘è‚²è¿Ÿç¼“å„¿ç«¥çš„ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.

Synergy-based functional electrical stimulation and robotic-assisted for retraining reach-to-grasp in stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke survivors have long-term upper limb impairment, which impacts the quality of life (QOL) and social reintegration, but there is lack of effective therapeutic strategies and novel technologies. Customized multi-muscle functional electrical stimulation (FES) based on the muscle synergy of healthy adults and robotic-assisted therapy (RAT) have been proved efficacy respectively. Synergy-based FES combined with RAT can be a novel and more effective therapy for upper limb recovery of stroke survivors from the perspective of synergistic enhancement. However, few studies have examined the effectiveness of combined synergy-based FES and RAT, especially for motor control evaluated by reach-to-grasp (RTG) movements. The main objective of the following research protocol is to evaluate the effectiveness and efficacy, as well as adoptability, of FES-RAT and FES or RAT rehabilitation program for upper limb function improvement after stroke. METHODS: This will be an assessor-blinded randomized controlled trial involving a 12-week intervention and a 6-month follow-up. Stratified randomization will be used to equally and randomly assign 162 stroke patients into the FES + conventional rehabilitation program (CRP) group, RAT + CRP group and FES-RAT + CRP group. Interventions will be provided in 5 sessions per week, with a total of 60 sessions. The primary outcome measurements will include the Fugl-Meyer Assessment and Biomechanical Assessment of RTG movements. The secondary outcome measurements will include quality of life and brain neuroplasticity assessments by MRI. Evaluations will be performed at five time points, including at baseline, 6 weeks and 12 weeks from the start of treatment, and 3 months and 6 months following the end of treatment. A two-way analysis of variance with repeated measures will be applied to examine the main effects of the group, the time factor and group-time interaction effects. DISCUSSION: The results of the study protocol will provide high quality evidence for integrated synergy-based FES and RAT, and synergy-based FES alone and guide the design of more effective treatment methods for stroke rehabilitation. TRIAL REGISTRATION: ChiCTR2300071588.

[Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome"].

OBJECTIVE: To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". METHODS: Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. RESULTS: After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). CONCLUSION: Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Decreased syntaxin17 expression contributes to the pathogenesis of acute pancreatitis in murine models by impairing autophagic degradation.

Acute pancreatitis (AP) is an inflammatory disease of the exocrine pancreas. Disruptions in organelle homeostasis, including macroautophagy/autophagy dysfunction and endoplasmic reticulum (ER) stress, have been implicated in human and rodent pancreatitis. Syntaxin 17 (STX17) belongs to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) subfamily. The Qa-SNARE STX17 is an autophagosomal SNARE protein that interacts with SNAP29 (Qbc-SNARE) and the lysosomal SNARE VAMP8 (R-SNARE) to drive autophagosome-lysosome fusion. In this study, we investigated the role of STX17 in the pathogenesis of AP in male mice or rats induced by repeated intraperitoneal injections of cerulein. We showed that cerulein hyperstimulation induced AP in mouse and rat models, which was characterized by increased serum amylase and lipase activities, pancreatic edema, necrotic cell death and the infiltration of inflammatory cells, as well as markedly decreased pancreatic STX17 expression. A similar reduction in STX17 levels was observed in primary and AR42J pancreatic acinar cells treated with CCK (100 nM) in vitro. By analyzing autophagic flux, we found that the decrease in STX17 blocked autophagosome-lysosome fusion and autophagic degradation, as well as the activation of ER stress. Pancreas-specific STX17 knockdown using adenovirus-shSTX17 further exacerbated pancreatic edema, inflammatory cell infiltration and necrotic cell death after cerulein injection. These data demonstrate a critical role of STX17 in maintaining pancreatic homeostasis and provide new evidence that autophagy serves as a protective mechanism against AP.

Filtration of the preferred catalyst for reverse water-gas shift among Rhn- (n = 3-11) clusters by mass spectrometry under variable temperatures.

The key to optimizing energy-consuming catalytic conversions lies in acquiring a fundamental understanding of the nature of the active sites and the mechanisms of elementary steps at an atomically precise level, while it is challenging to capture the crucial step that determines the overall temperature of a real-life catalytic reaction. Herein, benefiting from a newly-developed high-temperature ion trap reactor, the reverse water-gas shift (CO2 + H2 → CO + H2O) reaction catalyzed by the Rhn- (n = 3-11) clusters was investigated under variable temperatures (298-783 K) and the critical temperature that each elementary step (Rhn- + CO2 and RhnO- + H2) requires to take place was identified. The Rh4- cluster strikingly surpasses other Rhn- clusters to drive the catalysis at a mild starting temperature (∼440 K). This finding represents the first example that a specifically sized cluster catalyst that works under an optimum condition can be accurately filtered by using state-of-the-art mass spectrometric experiments and rationalized by quantum-chemical calculations.

Activatable fluorescent probes for real-time imaging-guided tumor therapy.

Surgery and drug therapy are the two principal options for cancer treatment. However, their clinical benefits are hindered by the difficulty of accurate location of the tumors and timely monitoring of the treatment efficacy of drugs, respectively. Rapid development of imaging techniques provides promising tools to address these challenges. Compared with conventional imaging techniques such as magnetic resonance imaging and computed tomography etc., fluorescence imaging exhibits high spatial resolution, real-time imaging capability, and relatively low costs devices. The advancements in fluorescent probes further accelerate the implementation of fluorescence imaging in tumor diagnosis and treatment monitoring. In particular, the emergence of site-specifically activatable fluorescent probes fits the demands of tumor delineation and real-time feedback of the treatment efficacy. A variety of small molecule probes or nanoparticle-based probes have been developed and explored for the above-mentioned applications. This review will discuss recent advances in fluorescent probes with a special focus on activatable nanoprobes and highlight the potential implementation of activatable nanoprobes in fluorescence imaging-guided surgery as well as imaging-guided drug therapy.

[Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism].

OBJECTIVE: To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism. METHODS: Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot. RESULTS: The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61. CONCLUSION: Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.

MCM4 is a novel prognostic biomarker and promotes cancer cell growth in glioma.

Background: Gliomas account for 75% of all primary malignant brain tumors in adults and result in high mortality. Accumulated evidence has declared the minichromosome maintenance protein complex (MCM) gene family plays a critical role in modulating the cell cycle and DNA replication stress. However, the biological function and clinic characterization of nine MCM members in low-grade glioma are not yet clarified. Methods: In this study, we utilized diverse public databases, including The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, Human Protein Atlas (HPA), Linkedomics, cbioportal, Tumor and Immune System Interaction Database (TISIDB), single-sample GSEA (ssGSEA), Tumor Immune Estimation Resource (TIMER), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal databases to explore the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, tumor mutational burden (TMB), immune subtype, immune cell infiltration, immune modulator and drug sensitivity of nine MCMs. Afterward, qRT-PCR was utilized to detect the expression of the MCM family in glioblastoma multiforme (GBM) cell lines. The one-, three-, or five-year survival rate was predicted by utilizing a nomogram established by cox proportional hazard regression. Results: In this study, we found that nine MCMs were consistently up-regulated in glioma tissues and glioma cell lines. Elevated nine MCMs expressions were significantly correlated with a higher tumor stage, isocitrate dehydrogenase (IDH) mutates, 1p/19q codeletion, histological type, and primary therapy outcome. Survival analyses showed that higher expression of MCM2-MCM8 (minichromosome maintenance protein2-8) and MCM10 (minichromosome maintenance protein 10) were linked with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. On the other hand, up-regulated MCM2-MCM8 and MCM10 were significantly associated with shorter disease-specific survival (DSS) in glioma patients. Univariate and multivariate analyses revealed that MCM2 (minichromosome maintenance protein2), MCM4 (minichromosome maintenance protein 4), MCM6 (minichromosome maintenance protein 6), MCM7 (minichromosome maintenance protein 7) expression and tumor grade, 1p/19q codeletion, age, and primary therapy outcome were independent factors correlated with the clinical outcome of glioma patients. More importantly, a prognostic MCMs model constructed using the above five prognostic genes could predict the overall survival of glioma patients with medium-to-high accuracy. Furthermore, functional enrichment analysis indicated that MCMs principal participated in regulating cell cycle and DNA replication. DNA copy number variation (CNV) and DNA methylation significantly affect the expression of MCMs. Finally, we uncover that MCMs expression is highly correlated with immune cell infiltration, immune modulator, TMB, and drug sensitivity. Conclusions: In summary, this finding confirmed that MCM4 is a potential target of precision therapy for patients with glioma.

Multiple primary malignancies - hepatocellular carcinoma combined with splenic lymphoma: A case report.

BACKGROUND: Primary liver cancer is one of the most common malignant tumours, while primary splenic lymphoma is a rare malignancy. Thus, cases of hepatocellular carcinoma (HCC) combined with splenic lymphoma are extremely rare. CASE SUMMARY: We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound. Contrast-enhanced computed of the abdomen revealed a circular, low-density, shallow mass (approximately 2.6 cm in diameter) in the left intrahepatic lobe and multiple round, low-density shadows in the spleen with clear boundaries (maximum diameter 7.6 cm). Based on the characteristic clinical symptoms and explicit radiological findings, the clinical diagnosis was HCC with metastasis to the liver portal, retroperitoneal lymph nodes, and spleen. After transcatheter arterial chemoembolization and sequential radiofrequency ablation, the -fetoprotein level returned to the normal range, and the hepatitis B cirrhosis improved. In addition, splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma, which went into remission after chemotherapy. CONCLUSION: HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed. Better understanding would facilitate early diagnosis, treatment and prognosis.

Pore-forming protein ßγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients.

During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, ßγ-CAT (a complex of non-lens ßγ-crystallin and trefoil factor) is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid (FA) uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and FAs, called nutrisomes, were released in the presence of ßγ-CAT. These specific nutrient vesicles were readily taken up by starved myoblast cells to support their survival. The results uncovered that pore-forming protein ßγ-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.

Comparison of operation time, efficacy and safety between through-the-scope stent and over-the-while stent in malignant central airway obstruction: a multi-center randomized control trial.

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent. Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety. Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance. Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation. Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431.

Impact of Sulfur Fumigation on Ginger: Chemical and Biological Evidence.

We previously found that sulfur fumigation, a commonly used controversial method for the post-harvest handling of ginger, induces the generation of a compound in ginger, which was speculated to be a sulfur-containing derivative of 6-shogaol based on its mass data. However, the chemical and biological properties of the compound remain unknown. As a follow-up study, here we report the chemical structure, systemic exposure, and anticancer activity of the compound. Chromatographic separation, nuclear magnetic resonance analysis, and chemical synthesis structurally elucidated the compound as 6-gingesulfonic acid. Pharmacokinetics in rats found that 6-gingesulfonic acid was more slowly absorbed and eliminated, with more prototypes existing in the blood than 6-shogaol. Metabolism profiling indicated that the two compounds produced qualitatively and quantitatively different metabolites. It was further found that 6-gingesulfonic acid exerted significantly weaker antiproliferative activity on tumor cells than 6-shogaol. The data provide chemical and biological evidence that sulfur fumigation may impair the healthcare functions of ginger.

Key pathways and genes in hepatitis B virus-related liver inflammation: Expression profiling and bioinformatics analysis.

Chronic hepatitis B virus infection has become a major public health issue worldwide, which can lead to liver inflammation, fibrosis, and hepatocellular carcinoma. According to the inflammation activity, liver tissues can be divided into 5 grades (G0-G4). However, the mechanism of the development of liver inflammation remains unclear. In our study, expression profiling by microarray and bioinformatics technology was used to systemically identify differentially expressed genes (DEGs) between low grades (G0-G1) and high (G2-G4) grades of liver inflammation. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network construction were performed for further identification of the key functions, pathways, and hub genes that might play important roles in the inflammation development. A total of 1982 DEGs were identified, consisting of 1220 downregulated genes and 762 upregulated genes. GO analysis revealed the DEGs were mainly enriched in GO terms that related to neutrophil activation and degranulation. MAPK1, ITGA2, CDK2, TGFB1, CDKN2A, MTOR, IL6, PCNA, OAS2, and EP300 were hub genes that had the highest centricity and might be potential markers for inflammation development. This study identified the differentially expressed genes between different grades of inflammation, which would enlighten the study that focuses on the mechanism of liver inflammation development.

Growth dynamics of breast cancer stem cells: effects of self-feedback and EMT mechanisms.

Breast cancer stem cells (BCSCs) with the ability to self-renew and differentiate have been identified in primary breast cancer tissues and cell lines. The BCSCs are often resistant to traditional radiation and/or chemotherapies. Previous studies have also shown that successful therapy must eradicate cancer stem cells. The purpose of this paper is to develop a mathematical model with self-feedback mechanism to illustrate the issues regarding the difficulties of absolutely eliminating a breast cancer. In addition, we introduce the mechanism of the epithelial-mesenchymal transition (EMT) to investigate the influence of EMT on the effects of breast cancer growth and treatment. Results indicate that the EMT mechanism facilitates the growth of breast cancer and makes breast cancer more difficult to be cured. Therefore, targeting the signals involved in EMT can halt tumor progression in breast cancer. Finally, we apply the experimental data to carry out numerical simulations and validate our theoretical conclusions.

A pore-forming protein drives macropinocytosis to facilitate toad water maintaining.

Maintaining water balance is a real challenge for amphibians in terrestrial environments. Our previous studies with toad Bombina maxima discovered a pore-forming protein and trefoil factor complex ßγ-CAT, which is assembled under tight regulation depending on environmental cues. Here we report an unexpected role for ßγ-CAT in toad water maintaining. Deletion of toad skin secretions, in which ßγ-CAT is a major component, increased animal mortality under hypertonic stress. ßγ-CAT was constitutively expressed in toad osmoregulatory organs, which was inducible under the variation of osmotic conditions. The protein induced and participated in macropinocytosis in vivo and in vitro. During extracellular hyperosmosis, ßγ-CAT stimulated macropinocytosis to facilitate water import and enhanced exosomes release, which simultaneously regulated aquaporins distribution. Collectively, these findings uncovered that besides membrane integrated aquaporin, a secretory pore-forming protein can facilitate toad water maintaining via macropinocytosis induction and exocytosis modulation, especially in responses to osmotic stress.