Persistent urban heat.

Urban surface and near-surface air temperatures are known to be often higher than their rural counterparts, a phenomenon now labeled as the urban heat island effect. However, whether the elevated urban temperatures are more persistent than rural temperatures at timescales commensurate to heat waves has not been addressed despite its importance for human health. Combining numerical simulations by a global climate model with a surface energy balance theory, it is demonstrated here that urban surface and near-surface air temperatures are significantly more persistent than their rural counterparts in cities dominated by impervious materials with large thermal inertia. Further use of these materials will result in even stronger urban temperature persistence, especially for tropical cities. The present findings help pinpoint mitigation strategies that can simultaneously ameliorate the larger magnitude and stronger persistence of urban temperatures.

The value of ICG-guided left colon vascular variation and anatomical rules for the radical resection of proctosigmoid colon cancer.

Objective: During laparoscopic radical resection for proctosigmoid colon cancer (PCC), surgeons could inadvertently damage the arteries when following the operation path.This study investigated the variations in left colon blood vessels in order to guide the scientific protection of the marginal artery (MA) during laparoscopic surgery for PCC. Methods: Data from seven patients who underwent inferior mesenteric artery (IMA) angiography were included as imaging references to preliminarily explore the vascular structure and variation in the left colon. The clinical video data of 183 PCC patients were retrospectively analyzed to observe intraoperative MA injury. Meanwhile, a prospective cohort of 96 patients with the same disease underwent intraoperative indocyanine green (ICG) fluorescence imaging of the peripheral sigmoid artery network, the variation of marginal arteries was summarized, and the distance between vessels and the bowel was measured at different levels. Patients were divided into 'ICG group' and 'non-ICG group' according to whether ICG guidance was performed, and perioperative conditions were compared between the two groups. Taking the integrity of lymph node dissection into consideration, 18 patients underwent carbon nanonode tracing. This study was conducted under the standard consent and ethical approval of the Ethics Committee of our center. Results: 7 patients with IMA angiography shared some vascular structures, defined as 'Dangerous Triangle' and 'Secure Window'. Through intraoperative observation, the primary arch was typically located 4.2 (2.3-6.0) cm away from the intestinal canal, and 5.21% (5/96) patients had poor anastomosis at the primary arch. Moreover, secondary vascular arches (6.4 (4.6-10.0) cm from the intestinal wall) were observed in 38.54% of patients. MA injury was identified in 2 of 183 cases, and the ischemic bowel was timely dissected, whereas no such injury occurred during ICG fluorescenceguided surgery. Guided by carbon nanoparticles, the integrity of lymph node dissection can be maintained while preserving the secondary arch in all patients. Conclusions: This study demonstrated the benefits of ICG guidance in protecting the intestinal blood supply in laparoscopic PCC surgery. By enhancing the understanding of primary and secondary vascular arches, secure windows, and dangerous triangles, surgeons can safely optimize the surgical path during surgery.

Refined assessment of space-time changes, influencing factors and socio-economic impacts of the terrestrial ecosystem quality: A case study of the GBA.

The terrestrial ecosystem is the cradle of energy and material basis for human survival and development. However, there are large research deficits in accurately and finely depicting the quality of the terrestrial ecosystem (QTE) and assessing its changing triggers' contribution. Here, we summarized three major principles for selecting image sources in remote sensing data fusion. A continuous 30-m net vegetation productivity (NPP) dataset during 2000-2019 for the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) was derived by using the Carnegie-Ames-Stanford approach model and pre-fused normalized difference vegetation index. The factors' contributions to the QTE changes were quantitatively assessed. The role of the QTE in affecting the socio-economic and its behind mechanisms was quantitatively investigated. The results showed that: (1) High-quality images sources are the preference for spatio-temporal fusion of remote sensing data. Images with close month, the same season and year, and sensors should be then selected. Images of different sensors with similar spectral bandwidth, the ones from adjacent years and seasons, can be alternately considered. (2) Fine-resolution NPP has higher accuracy than coarse-resolution NPP and has marked advantages in finely characterizing the QTE. In the past 20 years, the QTE in the GBA has shown a fluctuating increasing trend (0.20 Tg C/yr). (3) Human activities contributed 54.19% of the QTE changes in the GBA, and dominates the QTE changes in the central rapidly urbanizing areas. Residual factors accounted for an overall contribution ratio of 35.71%. Climate change dominants the peripheral forest variations in the GBA. (4) In the GBA, the improvement of QTE has a significant positive socio-economic impact, it contributes to the GDP increment firstly then the GDP aggregate indirectly. Our results highlight that it is of great urgent to estimate long-term continuous NPP with high spatio-temporal resolution globally. Controlling strategies should be implemented to reduce factitious impacts on QTE. High level of ecological and environmental protection promotes the sustainable development.

Development of prediction model to estimate future risk of ovarian lesions: A multi-center retrospective study.

Background: To develop the preoperative prediction of ovarian lesions using regression-based statistics analyses and machine learning methods based on multiple serological biomarkers in China. Methods: 1137 patients with ovarian lesions in Zhujiang Hospital and 518 patients in others hospital in China were randomly assigned to training, test and external validation cohorts. Five machine learning classifiers, including Random Forest (RF), Extreme Gradient Boosting (XGB), Support Vector Classifier (SVC), K-nearest Neighbor (KN), Multi-Layer Perceptron (MLP) and the Lasso-Logistics prediction model (LLRM) were used to derive diagnostic information from 23 predictors. Results: The RF model had a high diagnostic value (AUC = 0.968) in predicting benign and malignant ovarian disease. Age and MLR were also potential diagnostic indicators for predicting ovarian disease except tumor indicators. The RF model well distinguished borderline ovarian tumors (AUC = 0.742). The RFM had a high predictive power to identify ovarian serous adenocarcinoma (AUC = 0.943) and ovarian endometriosis cysts (AUC = 0.914). Conclusions: The RF models can effectively predict adnexal lesions, promising to be adjuncts to the preoperative prediction of ovarian cancer.

"Caudal to cranial" versus "medial to lateral" approach in laparoscopic right hemicolectomy with complete mesocolic excision for the treatment of stage II and III colon cancer: perioperative outcomes and 5-year prognosis.

The purpose of this study was to compare the "caudal to cranial" (CC) versus "medial to lateral" (ML) approach for laparoscopic right hemicolectomy. Pertinent data from all patients with stage II and III between January 2015 and August 2017 were entered into a retrospective database. A total of 175 patients underwent the ML (N = 109) or CC approach (N = 66). Patient characteristics were equivalent between groups. The CC group showed a shorter surgical time 170.00 (145.00, 210.00) vs. (206.50 (178.75, 226.25) min) than the ML group (p < 0.001). The time to oral intake was shorter in the CC group than in the ML group ((3.00 (1.00, 4.00) vs. 3.00 (2.00, 5.00) days; p = 0.007). For the total harvested lymph nodes, there was no statistical significance between the CC group 16.50 (14.00, 21.25) and the ML group 18.00 (15.00, 22.00) (p = 0.327), and no difference was found in the positive harvested lymph nodes (0 (0, 2.00) vs. 0 (0, 1.50); p = 0.753). Meanwhile, no differences were found in other perioperative or pathological outcomes, including blood loss and complications. For 5-year prognosis, overall survival rates were 75.76% in the CC group and 82.57% in the ML group (HR 0.654, 95% CI 0.336-1.273, p = 0.207); disease-free survival rates were 80.30% in the CC group and 85.32% in the ML group (HR 0.683, 95% CI 0.328-1.422, p = 0.305). Both approaches were safe and feasible and resulted in excellent survival. The CC approach was beneficial in terms of the surgical time and time to oral intake.

Ultrasound-based prediction of preoperative core biopsy categories in solid breast tumor using machine learning.

Background: The American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) used with ultrasonography cannot guide the individual management of solid breast tumors, but preoperative core biopsy categories (CBCs) can. We aimed to use machine learning to analyze clinical and ultrasonic features for predicting CBCs and to aid in the development of a new ultrasound (US) imaging reporting system for solid tumors of the breast. Methods: This retrospective study included women with solid breast tumors who underwent US-guided core needle biopsy from March 1, 2019, to December 31, 2019. All patients were randomly assigned to a training or validation cohort (7:3 ratio). CBC was predicted using 5 machine learning models: random forest (RF), support vector machine (SVM), k-nearest-neighbor (KNN), multilayer perceptron (MLP), and ridge regression (RR). In the validation cohort, the area under the curve (AUC) and accuracy were ascertained for every algorithm. Based on AUC values, the optimal algorithm was determined, and the features' importance was depicted. Results: A total of 1,082 female patients were included (age range, 12-96 years; mean age ± standard deviation, 42.22±13.37 years). The proportion of the 4 CBCs was 4% (44/1,185) for the B1 group, 60% (714/1,185) for the B2 group, 5% (57/1,185) for the B3 group, and 31% (370/1,185) for the B5 group. In the validation cohort, AUCs of the optimal algorithm constructed RF were 0.78, 0.88, 0.64, and 0.92 for B1, B2, B3, and B5, respectively, with an accuracy of 0.82. Conclusions: Machine learning could strongly predict CBC, particularly in B2 and B5 categories of solid breast tumors, with RF being the optimal machine learning model.

Primary extra-gastrointestinal stromal tumor of retroperitoneum: Clinicopathologic characteristics and prognosis of six cases.

Aim: This study investigates the clinicopathological features and prognostic genic biomarker factors of primary retroperitoneal extra-gastrointestinal stromal tumors (EGISTs). Methods: The clinicopathological data of six patients with primary retroperitoneal EGIST were analyzed, including cell type (epithelioid or spindle), mitoses, and the presence of intratumoral necrosis and hemorrhage. Mitoses were counted and summed from 50 high power fields (HPFs). Mutations of exons 9, 10, 11, 13, 14, and 17 of the C-kit genes and those of exons 12 and 18 of the PDGFRA gene were examined. Follow-up was performed via telephone, and all outpatient records were reviewed. The last follow-up date was February 2022, the median follow-up was 27.5m and the postoperative status, medication, and survival of the patients were recorded. Result: The patients were treated with radical intent. Four cases (patients 3, 4, 5, and 6) underwent multivisceral resection for encroachment on the adjacent viscera. The postoperative pathological results demonstrated that all biopsy specimens were negative for S-100 and desmin, and positive for DOG1 and CD117. Additionally, four patients (case 1, 2, 4, and 5) were positive for CD34, four (case 1, 3, 5, and 6) were positive for SMA, four (case 1, 4, 5, and 6) had >5/50 HPFs, and three (case 1, 4, and 5) had Ki67 >5%. According to the modified National Institutes of Health (NIH) guidelines, all patients were graded as high-risk cases. By exome sequencing, exon11 mutations were detected in the six patients, while exon10 mutations were detected in two cases (patients 4 and 5). The median follow-up time was 30.5 (11-109) months, with only one fatality at 11 months. Conclusion: Retroperitoneal EGIST is a rare mesenchymal tumor that is difficult to distinguish from other retroperitoneal tumors. To diagnose this highly malignant tumor, low-threshold suspicion is necessary, and Kit and PDGFRA gene mutations should be routinely tested to confirm the diagnosis and guide subsequent treatment.

Highly Integrated µGC Based on a Multisensing Progressive Cellular Architecture with a Valveless Sample Inlet.

Microscale gas chromatographs (µGCs) promise in-field analysis of volatile organic compounds (VOCs) in environmental and industrial monitoring, healthcare, and homeland security applications. As a step toward addressing challenges with performance and manufacturability, this study reports a highly integrated monolithic chip implementing a multisensing progressive cellular architecture. This architecture incorporates three µGC cells that are customized for different ranges of analyte volatility; each cell includes a preconcentrator and separation column, two complementary capacitive detectors, and a photoionization detector (PID). An on-chip carrier gas filter scrubs ambient air for the analysis. The monolithic chip, with all 16 components, is 40.3 × 55.7 mm2 in footprint. To accommodate surface adsorptive and low-volatility analytes, the architecture eliminates the commonly used inlet valve, eliminating the need for chemically inactive surfaces in the valves and pumps, allowing the use of standard parts. Representative analysis is demonstrated from a nonpolar 14-analyte mixture, a polar 12-analyte mixture, and a 3-phosphonate ester mixture, covering a wide vapor pressure range (0.005-68.5 kPa) and dielectric constant range (1.8-23.2). The three types of detectors show highly complementary responses. Quantitative analysis is shown in the tens to hundreds ppb range. With 200 mL samples, the projected detection limits reach 0.12-4.7 ppb. Limited tests performed at 80% humidity showed that the analytes with vapor pressures <12 kPa were unaffected. A typical full run takes 28 min and consumes 2.3 kJ energy for the fluidic elements (excluding electronics). By eliminating chip-to-chip fluidic interconnections and requiring just one custom-fabricated element, this work presents a path toward high-performance and highly manufacturable µGCs.

Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

Retraction Notice to: Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma.

[This retracts the article DOI: 10.1016/j.omtn.2021.01.019.].

An innovative and convenient technique to reduce anastomotic leakage after double stapling anastomosis: laparoscopic demucositized suture the overlapping point of the "dog ear" area.

Anastomotic leakage (AL) is a major cause of postoperative morbidity and mortality in the treatment of colorectal cancer. The aim of this study was to investigate an innovative and convenient technique of laparoscopic demucositized suture the overlapping point of the "dog ear" area after the double stapling anastomosis (lds-DSA), as an improved alternative for conventional DSA, and whether it could reduce the AL rate in laparoscopic anterior resection (Lapa-AR). Between January 2018 and December 2020, a total of 245 patients who underwent Lapa-AR for the treatment of adenocarcinoma of the sigmoid colon or rectal cancer were divided into the lsd-DSA group (n = 99) and the DSA group (n = 146). Data were analyzed retrospectively. Morbidity, AL rate and other perioperative outcomes were compared between the two groups. Patient demographics, preoperative comorbidity, preoperative chemoradiotherapy, tumor size, stage, and other operative details were comparable between the two groups. There was no difference in surgical time between the two groups (196.41 ± 76.71 vs. 182.39 ± 49.10 min, p = 0.088). The overall complication rate was also without a difference (11/99, 11.11% vs. 21/146, 14.38%, p = 0.456), but AL rate significantly lower in the lsd-DSA group than in the DSA group (2/99, 2.02% vs. 12/146, 8.22%, p = 0.040). For other perioperative outcomes, the lsd-DSA group shortened the total and postoperative hospital stay, and the time to pull out drainage tube than in the DSA group. Our comparative study demonstrates lds-DSA to have a better short-term outcome in reducing AL compared with DSA. This technique could be an alternative approach to maximize the patients' benefit in Lapa-AR.

Traditional Patchouli essential oil modulates the host's immune responses and gut microbiota and exhibits potent anti-cancer effects in ApcMin /+ mice.

Patchouli Essential Oil (PEO) has been used as a scent for various healing purposes since the ancient Egyptian period. The primary source of the oil is Pogostemon cablin (PC), a medicinal plant for treating gastrointestinal symptoms. However, the pharmacological function has not been addressed. Here, we report the cancer prevention and gut microbiota (GM) modulating property of PEO and its derivatives patchouli alcohol (PA) and pogostone (PO) in the ApcMin /+ colorectal cancer mice model. We found that PEO, PA, and PO significantly reduced the tumor burden. At the same time, it strengthened the epithelial barrier, evidenced by substantially increasing the number of the goblet and Paneth cells and upregulation of tight junction and adhesion molecules. In addition, PEO, PA, and PO shifted M1 to M2 macrophage phenotypes and remodeled the inflammatory milieu of ApcMin /+ mice. We also found suppression of CD4+CD25+ and stimulation CD4+ CD8+ cells in the spleen, blood, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) of the treated mice. The composition of the gut microbiome of the drug-treated mice was distinct from the control mice. The drugs stimulated the short-chain fatty acids (SCFAs)-producers and the key SCFA-sensing receptors (GPR41, GPR43, and GPR109a). The activation of SCFAs/GPSs also triggered the alterations of PPAR-γ, PYY, and HSDCs signaling mediators in the treated mice. Our work showed that PEO and its derivatives exert potent anti-cancer effects by modulating gut microbiota and improving the intestinal microenvironment of the ApcMmin /+ mice.

Regional lymph nodes distribution pattern in central area of right-sided colon cancer: in-vivo detection and the update on the clinical exploration.

Distribution of regional lymph nodes (LNs) is decisive for the lymphadenectomy boundary in radical resection of right-sided colon cancer (RCC). Currently, the data of LNs in central area remains ambiguous and scarce. Herein we aim to provide a more detailed anatomical research on LNs surrounding the superior mesenteric vessels for RCC and investigated the metastasis rate. In this study, Carbon Nanoparticles (CNs) and Indocyanine Green (ICG) were used for regional LNs mapping by preoperative colonoscopic tattooing (PCT) and we laparoscopically observed the stained LNs distribution pattern. Lastly, 143 RCC patients who received a "superior mesenteric artery (SMA)-oriented" hemicolectomy were included to calculate the probability of LNs metastasis in our target area. 27 patients diagnosed as RCC (mean age 58.04 years, 17 male) were included. 14 patients underwent CNs injection and 13 patients consented to the ICG, while 4 cases suffered from imaging failure. The unequal number of the regional LNs located between SMV and SMA was detected in 22 cases (81.48%), posterior to SMV area in 6 cases (22.22%), and anterior to SMA in 16 cases (59.26%), respectively. The presence of LNs posterior to SMV was associated with the crossing pattern of ileocolic artery (χ2 = 4.24, P = 0.039). The probability of LNs metastasis in the above areas (target areas) was 2.10% (3/143). In conclusion, right-hemi colon-draining lymphatic vessels anteriorly/posteriorly traversed the SMV and arrived at the surface of SMA near the middle colonic artery (MCA) level, which highlights the potential need of removing mesenteric tissue in our target area on lymphatic resection.

Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis.

BACKGROUND: Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms. METHODS: Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database. RESULTS: First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis. CONCLUSIONS: The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.

Progressive Cellular Architecture in Microscale Gas Chromatography for Broad Chemical Analyses.

Gas chromatography is widely used to identify and quantify volatile organic compounds for applications ranging from environmental monitoring to homeland security. We investigate a new architecture for microfabricated gas chromatography systems that can significantly improve the range, speed, and efficiency of such systems. By using a cellular approach, it performs a partial separation of analytes even as the sampling is being performed. The subsequent separation step is then rapidly performed within each cell. The cells, each of which contains a preconcentrator and separation column, are arranged in progression of retentiveness. While accommodating a wide range of analytes, this progressive cellular architecture (PCA) also provides a pathway to improving energy efficiency and lifetime by reducing the need for heating the separation columns. As a proof of concept, a three-cell subsystem (PCA3mv) has been built; it incorporates a number of microfabricated components, including preconcentrators, separation columns, valves, connectors, and a carrier gas filter. The preconcentrator and separation column of each cell are monolithically implemented as a single chip that has a footprint of 1.8 × 5.2 cm2. This subsystem also incorporates two manifold arrays of microfabricated valves, each of which has a footprint of 1.3 × 1.4 cm2. Operated together with a commercial flame ionization detector, the subsystem has been tested against polar and nonpolar analytes (including alkanes, alcohols, aromatics, and phosphonate esters) over a molecular weight range of 32-212 g/mol and a vapor pressure range of 0.005-231 mmHg. The separations require an average column temperature of 63-68 °C within a duration of 12 min, and provide separation resolutions >2 for any two homologues that differ by one methyl group.

Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice.

We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1ß, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, 3 & 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.

Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma.

Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions and regulatory mechanisms of exosomal circRNAs induced by hypoxia remain poorly understood in lung adenocarcinoma (LUAD) development. Differentially expressed circRNAs were identified between exosomes extracted from hypoxic and normoxic conditions through microarray analysis. We focused on hsa-circ-0003439 found on chromosome 1 and derived from SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and thus we named it circSETDB1. We discovered that exosomes obtained from hypoxic LUAD cells improved the migration, invasion, and proliferation capacity of normoxic LUAD cells. circSETDB1 was found to be significantly upregulated in hypoxia-induced exosomes from LUAD cell lines compared with exosomes in the normal condition. Moreover, knockdown of circSETDB1 significantly inhibited cell malignant growth in vitro. Importantly, we showed that circSETDB1 was upregulated in serum exosomes in LUAD patients, and exosomal circSETDB1 levels were closely associated with disease stage. Finally, using RNA immunoprecipitation (RIP), bioinformatics, and luciferase reporter assays, we elucidated the implication of a circSETDB1/miR-7/specificity protein 1 (Sp1) axis in the development and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma.

Discovery of the bioactive peptides secreted by Bifidobacterium using integrated MCX coupled with LC-MS and feature-based molecular networking.

Probiotics can release many bioactive peptides that confer a myriad of benefits to the host health. However, exploring new bioactive peptides secreted by probiotics is hampered by lots of matrix-related interference peptides from the medium, and the low abundance. To this end, a new approach integrating mixed-mode cationic exchange based solid-phase extraction (MCX-SPE) coupled with liquid chromatography-mass spectrometry (LC-MS) and feature-based molecular networking (FBMN) was developed. FBMN's intuitive visualization results enabled twenty-five novel peptides to be quickly discovered and characterized from the cultures of three strains of Bifidobacterium, B. animalis, B. longum, and B. pseudolongum. Interestingly, four were uniquely secreted by B. animalis treated with gypenosides, and one showed ACE inhibitory effect with an IC50 value of 193.22 µM. Consequently, this approach could serve as a powerful tool for quickly discovering bioactive peptides from the complex metabolites of probiotics, which contributes to the development of functional foods and nutraceuticals.

Bifidobacterium animalis: the missing link for the cancer-preventive effect of Gynostemma pentaphyllum.

Colorectal cancer (CRC) ranks the third most common cancer type in both men and women. Besides the known genetic and epigenetic changes in the gut epithelial cells, we now know that disturbed gut microbes could also contribute to the onset and progression of CRC. Hence, keeping a balanced gut microbiota (GM) has become a novel pursue in the medical field, particularly in the area of gastrointestinal disorders. Gynostemma pentaphyllum (Gp) is a dietary herbal medicine. In our previous study, Gp saponins (GpS) displayed prebiotic and cancer-preventive properties through the modulation of GM in ApcMin/+ mice. However, the specific group(s) of GM links to the health effects of GpS remains unknown. To track down the missing link, we first investigated and found that inoculation with fecal materials from GpS-treated ApcMin/+ mice effectively reduces polyps in ApcMin/+ mice. From the same source of the fecal sample, we successfully isolated 16 bacterial species. Out of the 16 bacteria, Bifidobacterium animalis stands out as the responder to the GpS-growth stimulus. Biochemical and RNAseq analysis demonstrated that GpS enhanced expressions of a wide range of genes encoding biogenesis and metabolic pathways in B. animalis culture. Moreover, we found that colonization of B. animalis markedly reduces the polyp burden in ApcMin/+ mice. These findings reveal a mutualistic interaction between the prebiotic and a probiotic to achieve anticancer and cancer-preventive activities. Our result, for the first time, unveils the anticancer function of B. animalis and extend the probiotic horizon of B. animalis.