Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance.

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

A ThT Derivative as Zn2+ Sensor Based on DNA G-quadruplex.

In this report, we developed a sensing strategy based on ThT-E (a ThT derivative) and DNA G-quadruplex for the label-free detection of Zn2+. In the absence of Zn2+, there was a fluorescence enhancement of ThT-E by interaction with human telomere sequence. On the addition of Zn2+, Zn2+ induced a more compact antiparallel G-quadruplex to release ThT-E, resulting in fluorescence quenching. The detection limit was 0.6996 µM, and the fluorescence intensity showed a good linear relationship with the concentration of Zn2+ in the range of 0-10 µM. This sensing strategy which only needs to mix two kinds of materials has the characteristics of label-feel, simple operation, short response time, economical and efficient.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes to Sensitively Respond to HSO3- in Living Cells.

SO2, a gas signaling molecule, can be produced endogenously in mitochondria. Its hydrolysate, HSO3-, plays a key role in food preservation, cardiovascular relaxation, and other fields, suggesting that it is important to achieve its detection. Here, based on the Michael addition mechanism, four hemicyanine dye fluorescent probes (ETN, ETB, STB, and EIB) were designed and synthesized for responding to HSO3-. We evaluated the reaction ability of different probes with HSO3- and tried to explain the reasons for the significantly different response effects between probes and HSO3- according to the structure-activity relationship. The influence of different substituents of probes on the properties of mitochondria-targeting was also discussed. Finally, we screened out ETN as the optimal HSO3- probe due to its high sensitivity, rapid reactivity, and good mitochondria-targeting, and it could sensitively respond to HSO3- in living cells. The LODs of ETN for HSO3- were calculated by both absorption and fluorescence methods, respectively, which were 2.727 and 0.823 µM. Our work provided valuable references for designing strategies and potential tools for response to SO2 derivatives in biosystems.

"One stone, two birds": a mitochondria-targeted fluorescent probe for the detection of viscosity and HSO3- in living cells.

The material transport and physiological events of mitochondria need to be supported by a suitable microenvironment. For example, high viscosity will seriously hinder material exchange, and SO2, as the precursor of HSO3-, is an endogenous signal molecule that plays a key role in information transmission. It is very important to detect viscosity and HSO3- in mitochondria. Here, we developed a dual-responsive fluorescent probe (named Hcy-NT) to image the changes in mitochondrial viscosity and HSO3- in a "killing two birds with one stone" manner. Hcy-NT showed an OFF-ON fluorescence signal for the increase in cell viscosity induced by nystatin, while an ON-OFF fluorescence signal for intracellular and endogenous HSO3-. Its limits of detection for HSO3- were calculated by both absorption and fluorescence methods, which were 1.200 and 1.291 µM, respectively. This work provides a valuable tool for the study of viscosity and HSO3- related physiological processes and the diagnosis of potential diseases.

Study on the Efficacy of Sacubitril/Valsartan in Patients with Heart Failure with Preserved Ejection Fraction Undergoing Peritoneal Dialysis.

INTRODUCTION: Cardiovascular disease is the most common cause of death and morbidity in patients with end-stage renal disease. Sacubitril/valsartan (SAC/VAL) can reduce the risk of cardiovascular mortality among patients with heart failure (HF). The present study set out to evaluate the efficacy of SAC/VAL in the treatment of patients with HF with preserved ejection fraction (HFpEF) undergoing peritoneal dialysis (PD) (HFpEF&PD). METHODS: A total of 160 patients with HFpEF&PD were enrolled and randomly divided into the control group (N = 80) and SAC/VAL group (N = 80). The cardiac function efficacy, HF scoring efficacy, echocardiographic parameters, serological indicators, and 6-minute walking test were compared before and after treatment. RESULTS: After 6 months of treatment, the total number of patients who responded to treatment in the SAC/VAL group was higher than that of the control group in terms of cardiac function and HF scoring efficacy. After treatment, levels of early diastolic/late diastolic filling velocity and left ventricular ejection fraction were increased in both groups, while the levels of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, inter-ventricular septal diameter, and left ventricular posterior wall diameter were decreased; the NT-proBNP levels were diminished in both groups, while hemoglobin levels and the 6-minute walk distance were increased; the systolic blood pressure, diastolic blood pressure, and 24-h ultrafiltration volume were lowered in all patients. The changes in these indexes in the SAC/VAL group were more obvious than those in the controls. CONCLUSION: SAC/VAL can significantly improve cardiac function in patients with HFpEF&PD.

Room Temperature Anhydrous Suzuki-Miyaura Polymerization Enabled by C-S Bond Activation.

The Suzuki-Miyaura cross-coupling is one of the most important and powerful methods for constructing C-C bonds. However, the protodeboronation of arylboronic acids hinder the development of Suzuki-Miyaura coupling in the precise synthesis of conjugated polymers (CPs). Here, an anhydrous room temperature Suzuki-Miyaura cross-coupling reaction between (hetero)aryl boronic esters and aryl sulfides was explored, of which universality was exemplified by thirty small molecules and twelve CPs. Meanwhile, the mechanistic studies involving with capturing four coordinated borate intermediate revealed the direct transmetalation of boronic esters in the absence of H2 O suppressing the protodeboronation. Additionally, the room temperature reaction significantly reduced the homocoupling defects and enhanced the optoelectronic properties of the CPs. In all, this work provides a green protocol to synthesize alternating CPs.

Will climate change cause the global peatland to expand or contract? Evidence from the habitat shift pattern of Sphagnum mosses.

Peatlands play a crucial role in the global carbon cycle. Sphagnum mosses (peat mosses) are considered to be the peatland ecosystem engineers and contribute to the carbon accumulation in the peatland ecosystems. As cold-adapted species, the dominance of Sphagnum mosses in peatlands will be threatened by climate warming. The response of Sphagnum mosses to climate change is closely related to the future trajectory of carbon fluxes in peatlands. However, the impact of climate change on the habitat suitability of Sphagnum mosses on a global scale is poorly understood. To predict the potential impact of climate change on the global distribution of Sphagnum mosses, we used the MaxEnt model to predict the potential geographic distribution of six Sphagnum species that dominate peatlands in the future (2050 and 2070) under two greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5). The results show that the mean temperature of the coldest quarter, precipitation of the driest month, and topsoil calcium carbonate are the main factors affecting the habitat availability of Sphagnum mosses. As the climate warms, Sphagnum mosses tend to migrate northward. The suitable habitat and abundance of Sphagnum mosses increase extensively in the high-latitude boreal peatland (north of 50°N) and decrease on a large scale beyond the high-latitude boreal peatland. The southern edge of boreal peatlands would experience the greatest decline in the suitable habitat and richness of Sphagnum mosses with the temperature rising and would be a risk area for the transition from carbon sink to carbon source. The spatial-temporal pattern changes of Sphagnum mosses simulated in this study provide a reference for the development of management and conservation strategies for Sphagnum bogs.

Ethoxy-erianin phosphate and afatinib synergistically inhibit liver tumor growth and angiogenesis via regulating VEGF and EGFR signaling pathways.

The therapeutic efficacy of tyrosine kinase inhibitors (TKIs) on solid tumors is limited by drug resistance and side effects. Currently, the combination therapy comprises of TKIs and angiogenesis inhibitors have been corroborated as an effective approach in cancer therapy. Ethoxy-erianin phosphate (EBTP) is an anti-angiogenic compound with low toxicity obtained by structural modification of the natural product erianin. Here, we aimed to evaluate whether EBTP can cooperate with TKIs to inhibit the proliferation and angiogenesis of tumor cells and reduce toxic effects. First, CCK-8 results showed that EBTP can effectively inhibit the proliferation of liver cancer cell line HepG2. We combined EBTP with four TKIs (Bosutinib, Apatinib, Afatinib and Erlotinib) to treat HepG2 cells and CompuSyn software analysis suggested that EBTP/Afatinib(Afa)shows the best synergistic inhibitory effect. Meanwhile, EBTP/Afa can significantly suppress the proliferation, invasion, migration and angiogenesis of HepG2 and HUVECs. ELISA results revealed that EBTP/Afa inhibits the secretion of VEGF in HepG2. EBTP/Afa down-regulates the expression of VEGF, p-VEGFR1, p-VEGFR2 and p-EGFR in both HepG2 and HUVECs. Further, the supernatant of HepG2 cells treated with EBTP/Afa blocks the intracellular downstream signal transduction shared by VEGF and EGFR in HUVECs. Finally, EBTP/Afa significantly inhibits tumor growth and angiogenesis in vivo. To conclude, EBTP/Afa targets VEGF and EGFR signaling pathways in liver cancer cells and tumor vasculature, thereby inhibiting the proliferation, motion and angiogenesis of liver cancer cells. Overall, this study provides a new combined strategy for the clinical treatment of hepatocellular carcinoma.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

An artificial intelligence system for distinguishing between gastrointestinal stromal tumors and leiomyomas using endoscopic ultrasonography.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and gastrointestinal leiomyomas (GILs) are the most common subepithelial lesions (SELs). All GISTs have malignant potential; however, GILs are considered benign. Current imaging cannot effectively distinguish GISTs from GILs. We aimed to develop an artificial intelligence (AI) system to differentiate these tumors using endoscopic ultrasonography (EUS). METHODS: The AI system was based on EUS images of patients with histologically confirmed GISTs or GILs. Participants from four centers were collected to develop and retrospectively evaluate the AI-based system. The system was used when endosonographers considered SELs to be GISTs or GILs. It was then used in a multicenter prospective diagnostic test to clinically explore whether joint diagnoses by endosonographers and the AI system can distinguish between GISTs and GILs to improve the total diagnostic accuracy for SELs. RESULTS: The AI system was developed using 10 439 EUS images from 752 participants with GISTs or GILs. In the prospective test, 132 participants were histologically diagnosed (36 GISTs, 44 GILs, and 52 other types of SELs) among 508 consecutive subjects. Through joint diagnoses, the total accuracy of endosonographers in diagnosing the 132 histologically confirmed participants increased from 69.7 % (95 % confidence interval [CI] 61.4 %-76.9 %) to 78.8 % (95 %CI 71.0 %-84.9 %; P = 0.01). The accuracy of endosonographers in diagnosing the 80 participants with GISTs or GILs increased from 73.8 % (95 %CI 63.1 %-82.2 %) to 88.8 % (95 %CI 79.8 %-94.2 %; P = 0.01). CONCLUSIONS: We developed an AI-based EUS diagnostic system that can effectively distinguish GISTs from GILs and improve the diagnostic accuracy of SELs.

Sentinel Lymph Node Positive Rate Predicts Non-Sentinel Lymph Node Metastasis in Breast Cancer.

BACKGROUND: To investigate retrospectively an association between the number of metastatic sentinel lymph nodes (SLNs) per total number of SLNs per patient (i.e., the SLN positive rate, or SLN-PR) and non-SLN metastasis in breast cancer. METHODS: A large population (n = 2250) underwent SLN dissection from January 1, 2014 to January 1, 2020; 627 (27.87%) had at least one positive SLN (SLN+). Among these, 283 underwent axillary lymph node (ALN) dissection, and formed the test group. Four external validation groups comprised 43 patients treated in 2019. SLN mappings were examined using methylene blue and indocyanine green. Lymph node ultrasound, SLN-PR, and pathological characteristics were compared between patients with and without non-SLN metastasis. An SLN-PR cutoff value was calculated using receiver operating characteristic (ROC) curves. Associations between clinicopathological variables and SLN-PR with non-SLN metastasis were analyzed by multivariate logistic regression model. RESULTS: The median age was 47 years (IQR: 42-56 y). The median number of resected SLNs was 4. Patients with positive non-SLNs (126/283, 44.52%) had a median of 2 positive node. SLN-PR > 0.333 was a risk factor for non-SLN positivity (area under the ROC curve, 0.726); and carried significantly higher risk of non-SLN metastasis (P < 0.001). This was validated in the external group. CONCLUSIONS: SLN-PR > 0.333 was associated with greater risk of non-SLN metastasis. This provides a reference to non-SLN metastasis in patients with SLN metastasis, an indication for ALN dissection and choice of adjuvant treatment.

Recent advances in bioprobes and biolabels based on cyanine dyes.

As a functional dye, cyanine dye promotes the widespread application of bioprobes in the fields of medicine, genetics and environment, owing to its advantages of good photophysical properties, excellent biocompatibility and low toxicity to biological systems. Nowadays, it is mainly used in the fields of life sciences such as fluorescent labeling of biological macromolecules, disease diagnosis, immunoassay and DNA detection, all of which lie at the core of this review. First, we briefly introduced the characteristics and principles of the cyanine dye bioprobe. Afterward, we paid attention to the recent progress of cyanine dye bioprobes widely used in the 10 years from 2010 to 2020. The application of cyanine dyes as bioprobes with different identification elements, including enzymes, organelles, immunity and DNAs, was mainly summarized. Finally, this review gave an outlook on the future development trend of cyanine dye bioprobes. This facilitates the construction of a new type of multifunctional fluorescent probe and promotes its clinical application.

Expression profiles of miR-129 and miR-29a-5p in vascular calcification of patients with end-stage renal disease and the underlying correlation.

To analyze the changes and correlation of Mir-129 and Mir-29A-5p in vascular calcification in end-stage renal disease. A total of 97 patients with end-stage renal disease admitted to our hospital from August 2021 to August 2020 were selected as the research objects, and another 97 healthy people who underwent physical examination in our hospital during the same period were selected as the control study. According to X-ray examination, 97 subjects were divided into the vascular calcification group (39 cases) and the non-vascular calcification group (58 cases). Blood samples were extracted from each group, and the expressions of serum Mir-129 and Mir-29A-5p were detected by RT-PCR after centrifugation. The expressions of Mir-129 and Mir-29A-5p in healthy people with end-stage renal disease and vascular calcification were analyzed. To analyze the correlation of Mir-129 and Mir-29A-5p in vascular calcification of end-stage renal disease and its correlation with vascular calcification of end-stage renal disease. Compared with healthy people, the expression of Mir-129 and Mir-29A-5p in patients with the end-stage renal disease was abnormally increased, and there was a difference between the two groups (P<0.05). The expression levels of Mir-129 and Mir-29A-5p in patients with end-stage renal disease without vascular calcification were lower than those in the vascular calcification group, and there were differences between the two groups (P<0.05). Compared with mild vascular calcification, mir-129 and Mir-29A-5p expressions were higher in moderate and severe vascular calcification patients. In addition, compared with moderate patients, the expressions of Mir-129 and Mir-29a-5p were lower in mild patients and higher in severe patients. The expressions of Mir-129 and Mir-29A-5p in patients with mild and moderate vascular calcification were lower than those in patients with severe vascular calcification, and there were differences among the three groups (P < 0.05). Mir-129 and Mir-29A-5p were positively correlated with vascular calcification in end-stage renal disease (R =5.426, P=0.001). Mir-129 was positively correlated with vascular calcification in end-stage renal disease (r=0.649, P=0.001). Mir-29a-5p was positively correlated with vascular calcification in end-stage renal disease (r=0.529, P=0.001). Mir-129 and Mir-29a-5p showed high expression in the patients with end-stage renal disease, and they also increased with the occurrence of vascular calcification, and they showed a positive correlation in the vascular calcification of end-stage renal disease.

Expression of mir-29a-5p, sclerostin and fetuin-A in patients with chronic kidney disease and their correlation with vascular calcification.

The objective of the current study was to analyze the expression of mir-29a-5p, osteosclerotin and fetuin-A in patients with chronic kidney disease and their correlation with vascular calcification. For this purpose, 162 patients with chronic kidney disease treated in our hospital from January 2020 to January 2022 were selected retrospectively, and then 162 healthy people who underwent physical examination with our hospital in the same period were selected. The expressions of serum mir-29a-5p, sclerostin and fetuin-A were analyzed after fasting venous blood was drawn from the two groups. According to the coronary artery calcification score (CACS), patients with chronic kidney disease were divided into the calcification group (69 cases) and the non-calcification group (93 cases). The expressions of mir-29a-5p, sclerostin and fetuin-A in the two groups were analyzed, and the correlation between the three in chronic kidney disease and vascular calcification was analyzed. Results showed that compared with the control group, the expression of mir-29a-5p and sclerostin in the study group was higher, and the expression of fetuin-A was lower, the difference was statistically significant (P < 0.05); The expression of mir-29a-5p, sclerostin and fetuin-A in calcified group was higher than that in non-calcified group, and the expression of fetuin-A was lower (P < 0.05); Mir-29a-5p and sclerostin showed positive correlation (r=6.776, P=0.011); The expression of mir-29a-5p and fetuin-A showed negative correlation (r=-5.326, P=0.001); The expression of mir-29a-5p and sclerostin showed negative correlation (r=-9.677, P=0.001); Mir-29a-5p and sclerostin were positively correlated with vascular calcification (r=0.695, P=0.001; r=0.715, P=0.001), and fetuin-A was positively correlated with vascular calcification (r = -0.953, P = 0.001). Then, Mir-29a-5p, sclerostin and fetuin-A are abnormally expressed in chronic kidney disease. There is an abnormal correlation among them in chronic kidney disease, and they are correlated with vascular calcification.

3,4,5-O-tricaffeoylquinic acid alleviates ionizing radiation-induced injury in vitro and in vivo through regulating ROS/JNK/p38 signaling.

Ionizing radiation (IR) brings many health problems to humans, causing damage to the digestive system, hematopoietic system, and immune system. Natural compounds derived from plants have attracted widespread attention due to their low toxicity. Here, we found that 3,4,5-O-tricaffeoylquinic acid (tCQA) extracted from natural plant Azolla imbricata could significantly alleviate the systemic damage in mice caused by IR. In order to further explore the molecular mechanism of the radioprotective effect of tCQA, in vitro experiments confirmed that tCQA could attenuate the cytotoxic effect of IR on the colonic epithelial cell line NCM460 and alleviate the IR-induced mitochondrial dysfunction characterized by the decrease of mitochondrial transmembrane potential, ROS production, and caspase-dependent apoptosis. In addition, the generation of ROS induced by H2 O2 could also be reversed by tCQA. Then, Western blot demonstrated that tCQA could reverse the MAPK signaling pathway activated by IR. However, the inhibitory effect of tCQA on JNK and P38 levels activated by the JNK agonist anisomycin is not obvious; meanwhile, tCQA could inhibit the activation of JNK/P38 induced by H2 O2 , which suggests that tCQA might inhibit the JNK/P38 signaling pathway by reducing ROS. In short, tCQA inhibits the generation of ROS caused by IR, and then regulates the activity of caspase in the mitochondrial pathway by inhibiting the JNK/P38 signaling pathway, thereby alleviating the apoptosis of NCM460. This research provides an experimental basis for the development of new types of radioprotective agents for medical diagnosis and radiotherapy.

Defect-Free Alternating Conjugated Polymers Enabled by Room- Temperature Stille Polymerization.

The Stille cross-coupling polymerization is one of the most efficient synthetic methods for donor-acceptor (D-A) type π-conjugated polymers (CPs). Nevertheless, thermal-activation Stille polymerization readily produced homocoupling defects, resulting in batch-to-batch variations in copolymers quality and deteriorating the device performance of electronics and optoelectronics. Here, a room-temperature Stille-type polymerization was developed, the utility and generality of which were demonstrated by synthesis of twelve D-A CPs with high molecular weights. Importantly, the resultant copolymers possessed no homocoupling (hc) structural defects, while hc reactions were observed in the thermal-activation Stille reactions. Thus, the organic field-effect transistors (OFETs) based on the former exhibited twofold higher charge transport mobility (2.10 cm2  V-1 s-1 ), since it possessed stronger crystallinity and lower trap density of states (tDOS).

IL-8/CXCR2 mediates tropism of human bone marrow-derived mesenchymal stem cells toward CD133+ /CD44+ Colon cancer stem cells.

In cancer treatment, the most attractive feature of mesenchymal stem cells (MSCs) is it's homing to tumor tissues. MSC is an important part of the "colon cancer stem cell niche", but little research has been done on the tropism of human MSCs toward colon cancer stem cells (CCSCs). In this study, we first compared the effects of three tissue-derived MSCs (bone marrow, adipose tissue, and placenta) in vivo on colon tumor xenograft growth. Then, we analyzed the tropism of bone marrow-derived MSCs (BMSCs) toward normal intestinal epithelial cells (NCM460), parental colon cancer cells, CD133- /CD44-, and CD133+ /CD44+ colon cancer cells in vitro. Microarray analysis and in vitro experiments explored the mechanism of mediating the homing of BMSCs toward CCSCs. Compared with the parental and CD133- /CD44- colon cancer cells, CD133+ /CD44+ cells have a stronger ability to recruit BMSCs. In addition, BMSCs were significantly transformed into cancer-associated fibroblasts after being recruited by CCSCs. After coculture of BMSCs and CCSCs, the expression of interleukin (IL)-6, IL-8, IL-32, and CCL20 was significantly increased. Compared with parental strains, CD133- /CD44- cells, and NCM460, BMSC secreted significantly more IL-8 after coculture with CD133+ /CD44+ cells. Low concentration of IL-8 peptide inhibitors (100 ng/ml) and CXC receptor 2 (CXCR2) inhibitors have little effect on the migration of BMSCs, but can effectively weaken CCSC stemness and promote dormant CSCs in the coculture system to re-enter into the cell cycle. The endogenous IL-8 knockout in BMSCs or BMSCs loaded with IL-8 and/or CXCR2 inhibitors will make the therapy of BMSC targeting CCSCs function at its best.

The effect and mechanism of erianin on the reversal of oxaliplatin resistance in human colon cancer cells.

Multidrug resistance (MDR) is the main cause of chemotherapy failure in the treatment of colon cancer and the high expression of drug efflux protein P-gp is one of the main factors of MDR. P-gp expression is regulated by the signal transducer and activator of transcription 3 (STAT3) signaling pathway. In this study, human colon cancer oxaliplatin-resistant cells were treated with oxaliplatin combined with the natural product erianin. Then, we evaluated the impact of erianin on drug resistance, and explored the relationship between erianin-related oxaliplatin resistance and the Janus kinase 2/STAT3 signaling pathway in vitro. Our research showed that erianin could significantly inhibit the proliferation of human colon cancer oxaliplatin-resistant cells, and suppress the cell cycle of oxaliplatin-resistant cells in the G2/M phase, indicating that erianin could regulate the MDR phenotype of oxaliplatin-resistant cells, and its mechanism might be the inhibition of STAT3 signaling pathway and the significant reduction of P-gp expression. However, this study provides a theoretical basis for the clinical application of erianin in platinum-based chemotherapy for colon cancer.