Oncogenic GBX2 promotes the malignant behaviors of bladder cancer cells by binding to the ITGA5 promoter and activating its transcription.

In bladder cancer patients, metastasis after surgical resection and serious adverse reactions brought by cisplatin-based systemic chemotherapy make it urgent to explore novel therapeutic methods for improving the clinical outcomes of patients with unsuccessful first-line chemotherapy and disease progression. In this study, GBX2 has been recognized as a differentially expressed transcriptional factor between bladder cases with response to treatment and progressive disease based on online expression profile analysis. Higher GBX2 expression was correlated with poorer OS, DSS, and PFS in bladder cancer patients. GBX2 co-expressed genes were enriched in ECM regulation. ITGA5 was positively correlated with GBX2. GBX2 and ITGA5 were notably elevated in bladder cancer cells. GBX2 and ITGA5 similarly affected bladder cancer cell phenotypes via facilitating cell viability, migration, and invasion. By binding to the promoter region of ITGA5, GBX2 activated ITGA5 transcription, upregulating ITGA5 expression. In bladder cancer cells co-transfected with sh-GBX2 and ITGA5 oe, the inhibitory effects of GBX2 knockdown on bladder cancer cell malignant behaviors were partially eliminated by ITGA5 overexpression. In conclusion, GBX2 and ITGA5 serve as oncogenic factors, promoting the viability, migration, and invasion of bladder cancer cells. GBX2 exerts its functions by targeting the ITGA5 promoter region to activate ITGA5 transcription.

Organ damage evaluation in a temperature-controlled circulatory arrest rat model.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is commonly used in adult aortic surgery and pediatric complex congenital heart disease, and is associated with pathophysiological changes and postoperative complications. Here, a temperature-controlled circulatory arrest model in rats was established to study the suitable temperature of circulatory arrest by investigating the damage to body organs under different temperatures. METHODS: Thirty Sprague‒Dawley rats were randomly divided into 5 equal groups for DHCA experiments: I (15-20 °C), II (20-25 °C), III (25-30 °C), IV (normothermic cardiopulmonary bypass), and V (sham operation group). Blood gas analysis, homodynamic parameters, and intervals of cardiac recovery were measured at different time points in all groups. Morphological changes in intestinal tissue were observed under light and electron microscopes. Oxidative stress was measured by MPO activity, MDA, and SOD content. Tissue damage was confirmed by serum detection of ALT, AST, BUN, Cr, and LDH. To examine the inflammatory response, cytokines, including IL-1, IL-4, IL-10, IFN-γ, and TNF-α, were detected. RESULTS: The extracorporeal circulation technique caused damage to the body; the degree of the damage caused by the circulatory arrest technique may be related to circulating temperature, with the least amount of damage occurring at 20-25 °C compared to 15-20 °C and 25-30 °C. Ischemia and hypoxia can cause intestinal tissue damage, which manifests primarily as a loss of the intestinal mucosal barrier. Ischemic intestinal damage caused by DHCA was not associated with inflammation. CONCLUSION: The study provides new insights into the pathophysiologic mechanisms of DHCA.

Risk factors for venoarterial-extracorporeal membrane oxygenation related nosocomial infection in children after cardiac surgery. / 儿童心脏术后静脉-åŠ¨è„‰ä½“å¤–è†œè‚ºæ°§åˆç›¸å ³åŒ»é™¢å† æ„ŸæŸ“çš„å±é™©å› ç´ .

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support strategy for the treatment of critically ill children with reversible heart and lung failure, increasingly being used in patients with low cardiac output after cardiac surgery. However, the mortality of patients is closely related to the complications of ECMO, especially bleeding, thrombosis, and infection, ECMO-related nosocomial infection has become a challenge to the success of ECMO. This study aims to analyze the incidence and risk factors for venoarterial-ECMO (VA-ECMO)-related nosocomial infections in children after cardiac surgery. METHODS: We retrospectively collected the data of patients who underwent VA-ECMO treatment after pediatric cardiac surgery in the Second Xiangya Hospital of Central South University from July 2015 to March 2021, and divided them into an infected group and a non-infected group. The clinical characteristics of the 2 groups of patients, VA-ECMO-related nosocomial infection factors, pathogenic microorganisms, and patient mortality were compared. Logistic regression was used to analyze the risk factors for nosocomial infection related to VA-ECMO after cardiac surgery. RESULTS: Of the 38 pediatric patients, 18 patients (47.37%) had VA-ECMO related nosocomial infection, served as the infected group, including 7 patients with blood infections and 11 respiratory tract infections. Gram-negative pathogens (16 strains, 88.9%) were the main bacteria, such as Acinetobacter baumannii (6 strains), Klebsiella pneumoniae (3 strains), and Stenotrophomonas maltophilia (3 strains). Compared with the non-infected group (n=20), the infection group had longer time of cardiopulmonary bypass, time of myocardial block, and time of VA-ECMO assistance (All P<0.05). Multivariate logistic regression analysis showed that time of cardiopulmonary bypass (OR=1.012, 95% CI 1.002 to 1.022; P=0.021) was an independent risk factor for ECMO-related nosocomial infection. The number of surviving discharges in the infected group was less than that in the non-infected group (1 vs 11, P<0.05). CONCLUSIONS: Cardiopulmonary bypass time is an independent risk factor for VA-ECMO-related nosocomial infection in children after cardiac surgery. Shortening the duration of extracorporeal circulation may reduce the incidence of VA-EMCO-related nosocomial infections in children after cardic surgery. The occurrence of VA-ECMO-related nosocomial infections affects the number of patient's discharge alive.

The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial-mesenchymal transition.

BACKGROUND: Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial-mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. METHODS: Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. RESULTS: Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. CONCLUSIONS: In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.

Masked Alkyne Equivalents for the Synthesis of Mechanically Interlocked Polyynes*.

Polyyne polyrotaxanes, encapsulated cyclocarbon catenanes and other fascinating mechanically interlocked carbon-rich architectures should become accessible if masked alkyne equivalents (MAEs) can be developed that are large enough to prevent unthreading of a macrocycle, and that can be cleanly unmasked under mild conditions. Herein, we report the synthesis of a new bulky MAE based on t-butylbicyclo[4.3.1]decatriene. This MAE was used to synthesize a polyyne [2]rotaxane and a masked-polyyne [3]rotaxane by Cadiot-Chodkiewicz coupling. Glaser cyclo-oligomerization of the [2]rotaxane gave masked cyclocarbon catenanes. The unmasking behavior of the catenanes and rotaxanes was tested by photolysis at a range of UV wavelengths. Photochemical unmasking did not proceed cleanly enough to prepare extended encapsulated polyyne polyrotaxanes. We highlight the scope and challenges involved with this approach to interlocked carbon-rich architectures.

Detecting Mechanochemical Atropisomerization within an STM Break Junction.

We have employed the scanning tunneling microscope break-junction technique to investigate the single-molecule conductance of a family of 5,15-diaryl porphyrins bearing thioacetyl (SAc) or methylsulfide (SMe) binding groups at the ortho position of the phenyl rings (S2 compounds). These ortho substituents lead to two atropisomers, cis and trans, for each compound, which do not interconvert in solution under ambient conditions; even at high temperatures, isomerization takes several hours (half-life 15 h at 140 °C for SAc in C2Cl4D2). All the S2 compounds exhibit two conductance groups, and comparison with a monothiolated (S1) compound shows the higher group arises from a direct Au-porphyrin interaction. The lower conductance group is associated with the S-to-S pathway. When the binding group is SMe, the difference in junction length distribution reflects the difference in S-S distance (0.3 nm) between the two isomers. In the case of SAc, there are no significant differences between the plateau length distributions of the two isomers, and both show maximal stretching distances well exceeding their calculated junction lengths. Contact deformation accounts for part of the extra length, but the results indicate that cis-to-trans conversion takes place in the junction for the cis isomer. The barrier to atropisomerization is lower than the strength of the thiolate Au-S and Au-Au bonds, but higher than that of the Au-SMe bond, which explains why the strain in the junction only induces isomerization in the SAc compound.

Synthesis of Polyynes Using Dicobalt Masking Groups.

Extended triisopropylsilyl end-capped polyynes have been prepared from the corresponding tetracobalt complexes by removing the complexed dicobalt tetracarbonyldiphenylphosphinomethane (Co2(CO)4dppm) moieties. Unmasking of this "masked alkyne equivalent" was achieved under mild conditions with elemental iodine at room temperature, making it possible to obtain fragile polyynes with up to 20 contiguous sp-hybridized carbon atoms. The Co2(CO)4dppm moiety has a strong geometric and steric effect on the polyyne but does not have a marked electronic effect on the terminal alkyne, as indicated by NMR and IR spectroscopy, density functional theory calculations, and X-ray crystallography. An unusual "alkyne hopping" migration of the dicobalt group was noticed as a minor side reaction during copper-catalyzed Eglinton coupling.

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

BACKGROUNDS/AIMS: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. METHODS: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. RESULTS: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. CONCLUSION: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

Unexpected Interactions between Alkyl Straps and Pyridine Ligands in Sulfur-Strapped Porphyrin Nanorings.

Strapped or "basket-handle" porphyrins have been investigated previously as hemoglobin mimics and catalysts. The facial selectivity of their interactions with axial ligands is a sensitive test for noncovalent bonding. Here the binding of pyridyl ligands to zinc porphyrins with thioester-linked alkyl straps is investigated in solution by NMR spectroscopy and UV-vis titration, and in the solid state by X-ray crystallography. We expected that coordination of the axial ligand would occur on the less hindered face of the porphyrin, away from the strap. Surprisingly, attractive interactions between the strap and the ligand direct axial coordination to the strapped face of the porphyrin, except when the strap is short and tight. The strapped porphyrins were incorporated into π-conjugated cyclic porphyrin hexamers using template-directed synthesis. The strap and the sulfur substituents are located either inside or outside the porphyrin nanoring, depending on the length of the strap. Six-porphyrin nanorings with outwardly pointing sulfur anchors were prepared for exploring quantum interference effects in single-molecule charge transport.

Active-Metal Template Synthesis of a Halogen-Bonding Rotaxane for Anion Recognition.

The synthesis of an all-halogen-bonding rotaxane for anion recognition is achieved by using active-metal templation. A flexible bis-iodotriazole-containing macrocycle is exploited for the metal-directed rotaxane synthesis. Endotopic binding of a Cu(I) template facilitates an active-metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper-template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen-bond donors into the rotaxane's interlocked binding cavity to facilitate anion recognition.

Systematic Review and Meta-Analysis of benefits and risks between normothermia and hypothermia during cardiopulmonary bypass in pediatric cardiac surgery.

BACKGROUND: The controversy over the benefits between normothermic and hypothermic cardiopulmonary bypass (CPB) for children is still uncertain. The purpose of this systematic review and meta-analysis is to investigate the benefits and risks of normothermia comparing with hypothermia in pediatric cardiac surgery by randomized controlled trials. METHODS: Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies reported in English up to September 28, 2013. Eligible studies were those in which investigators enrolled pediatric patients, who had cardiac surgery, randomized them to normothermic or hypothermic CPB. We prespecified the use of random-effects models to calculate risk ratios and 95% CIs for binary variables, weighted mean difference (WMD) or standard mean difference and 95% CIs for continuous variables. We assessed heterogeneity using I(2). When heterogeneity was absent (I(2) = 0%), we used fixed-effects models. The endpoints were serum lactate, serum creatinine, duration of clamp, and duration of CPB in pediatrics who had cardiac surgery in normothermic CPB compared with those in hypothermic CPB. RESULTS: The initial search strategy identified 3910 citations, of which 10 trials compared pediatrics and seven trails were eligible. These seven trials included 419 participants from seven countries. The serum lactate and the serum creatinine had three time points. The outcomes had no different between normothermic group and hypothermic group. Duration of clamp (WMD = -10.793, 95% CI -28.89, 7.304; P = 0.242; I(2) = 86.6%; 204 patients, three trials) and duration of CPB (WMD = -41.780, 95% CI -89.523, 5.963; P = 0.086; I(2) = 95.6%; 199 patients, three trials) also had no significant differences between two groups. CONCLUSION: Normothermic CPB is as safe as hypothermic CPB in children requiring correction of simple congenital cardiac defects.

Nosocomial Infections During Extracorporeal Membrane Oxygenation in Pediatric Patients: A Multicenter Retrospective Study.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients with respiratory and/or cardiac failure. This study aimed to investigate the epidemiology and risk factors of nosocomial infection (NI) in pediatric patients who underwent ECMO for respiratory and/or circulatory failure. Methods: Medical records for patients that were administered underwent ECMO support at Xiangya Second Hospital of Central South University, The Sixth Medical Center of PLA General Hospital, and Children's Hospital Affiliation of Zhengzhou University, from September 2012 to December 2019 were retrospectively reviewed. Clinical data of the patients who developed NI were collected and analyzed. Univariate and multivariate logistic regressions were performed to identify the independent predictive factors of NI during ECMO. Results: A total of 54 first episodes of NI were identified in the 190 patients on ECMO, including 32 cases of respiratory tract infections, 20 cases of bloodstream infections, and 2 cases of surgical site wound infections. Gram-negative pathogens were the dominant pathogens isolated, accounting for 92.6% of the NI. The incidence of ECMO-related NI was 47.6 cases per 1,000 ECMO days. In the univariate logistic regression, ECMO mode, ECMO duration, ICU duration, and peritoneal dialysis were associated with the development of NI in patients with ECMO support. However, in the multivariate analysis, only ECMO duration (OR = 2.46, 95%CI: 1.10, 5.51; P = 0.029), ICU duration (OR = 1.35, 95%CI: 1.05, 1.59; P = 0.017) and peritoneal dialysis (OR = 2.69, 95%CI: 1.08, 5.73; P = 0.031) were the independent predictive factors for NI during ECMO support. Conclusion: This study identified the significant correlation between ECMO-related NI and ECMO duration, ICU duration, and peritoneal dialysis. Appropriate preventive measures are needed for hospitals to reduce the incidence of ECMO in pediatric patients.

Reliability and validity of the repetitive behavior scale-revised for young Chinese children with autism spectrum disorder in Jiangxi Province.

Restricted and repetitive behaviors (RRBs) are one of the two main diagnostic features of autism spectrum disorder (ASD). To date, a growing body of research on RRB in children with ASD has recently attracted academic attention. The Repetitive Behavior Scale-Revised (RBS-R) was primarily intended for use in evaluating RRBs observed in ASD. This study recruited 381 Chinese children with ASD aged 2-4 years to measure the reliability and validity of the RBS-R. Confirmatory factor analysis (CFA) was applied to the structuring models of the four proposed structural models, indicating that a 6-factor model demonstrated good internal consistency and the best fit based on common overall fit indices. These findings suggest the utility of the Chinese version of RBS-R.

Super-resolution RESOLFT microscopy of lipid bilayers using a fluorophore-switch dyad.

Dyads consisting of a photochromic switch covalently linked to a fluorescent dye allow the emission from the dye to be controlled by reversible photoisomerization of the switch; one form of the switch quenches fluorescence by accepting energy from the dye. Here we investigate the use of dyads of this type for super-resolution imaging of lipid bilayers. Giant unilamellar vesicles stained with the dyads were imaged with about a two-fold resolution-enhancement compared with conventional confocal microscopy. This was achieved by exciting the fluorophore at 594 nm, using a switch activated by violet and red light (405/640 nm).

5-Mercaptotetrazolyl-derived metallaboratranes.

The reactions of 1-tert butyl-5-thiotetrazole (HtttBu) with Na[BH4] provides Na[H2B(tttBu)2] (Na[1]) or Na[HB(tttBu)3] (Na[2]) in refluxing THF or xylene, respectively. Treating [RuCl(Ph)(CO)(PPh3)2] with Na[2] affords the triply-buttressed ruthenaboratrane [Ru(CO)(PPh3){κ4-B,S,S',S''-B(tttBu)3}] (5) whilst Na[1] with [IrCl(CO)(PPh3)2] or [RuCl(Ph)(CO)(PPh3)2] provides rare examples of doubly-buttressed metallaboratranes [IrH(CO)(PPh3){κ3-B,S,S'-BH(tttBu)2}] (7) and [Ru(CO)(PPh3)2{κ3-B,S,S'-BH(tttBu)2}] (12), the latter via the isolable thiotetrazoylborate complex [Ru(Ph)(CO)(PPh3){κ3-H,S,S'-H2B(tttBu)2}] (11).

Polyyne formation via skeletal rearrangement induced by atomic manipulation.

Rearrangements that change the connectivity of a carbon skeleton are often useful in synthesis, but it can be difficult to follow their mechanisms. Scanning probe microscopy can be used to manipulate a skeletal rearrangement at the single-molecule level, while monitoring the geometry of reactants, intermediates and final products with atomic resolution. We studied the reductive rearrangement of 1,1-dibromo alkenes to polyynes on a NaCl surface at 5 K, a reaction that resembles the Fritsch-Buttenberg-Wiechell rearrangement. Voltage pulses were used to cleave one C-Br bond, forming a radical, then to cleave the remaining C•-Br bond, triggering the rearrangement. These experiments provide structural insight into the bromo-vinyl radical intermediates, showing that the C=C•-Br unit is nonlinear. Long polyynes, up to the octayne Ph-(C≡C)8-Ph, have been prepared in this way. The control of skeletal rearrangements opens a new window on carbon-rich materials and extends the toolbox for molecular synthesis by atom manipulation.

Spironaphthoxazine switchable dyes for biological imaging.

Recent developments in super-resolution microscopy have significantly expanded the requirements for switchable dyes, leading to demand for specially designed molecular switches. We report the synthesis and characterization of a spironaphthoxazine photochromic switch (a derivative of palatinate purple) displaying high photoconversion (85-95%) under readily accessible 405 nm light, broad absorption in the visible, and excellent fatigue resistance. The indole substituent on this spironaphthoxazine is twisted out of conjugation with the naphthalene unit, yet it is crucial for activation with visible light. The open colored merocyanine form of the spironaphthoxazine reverts to the closed form with a lifetime of 4.7 s in dichloromethane at 20 °C; this thermal reversion is even faster in more polar solvents. The photochemical quantum yields for ring-opening and ring-closing are approximately 8% and 1%, respectively, in dichloromethane. The ring-opening and ring-closing reactions have been characterized by time-resolved infrared and transient absorption spectroscopies. Ring opening occurs rapidly (τ = 2.1 ns) and efficiently (∼90%) from the singlet excited state to form an intermediate (assigned as a cisoid merocyanine), which returns to the closed ground state (τ = 4.5 ns) in competition with relaxation to the transoid open form (τ = 40 ns). Photochemical ring closing is a faster and simpler process: the excited state proceeds to the closed spirooxazine with a time constant of 0.28 ns. This photochromic switch can be used in conjunction with commercial fluorescent dyes to create a small-molecule switchable fluorescent dyad that shows high contrast and good fatigue resistance in living cells. These properties make the dyads suitable for application in RESOLFT microscopy.

Correction: Spironaphthoxazine switchable dyes for biological imaging.

[This corrects the article DOI: 10.1039/C8SC00130H.].

Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats.

Inflammatory factors regulated by NF-κB play a significant role in PAH and myocardial hypertrophy. LXR activation may inhibit myocardial hypertrophy via suppressing inflammatory pathways; it is unknown whether LXR is also involved in PAH-induced myocardial hypertrophy or remodeling. To further explore the protective effect of LXR in PAH-induced cardiac hypertrophy and remodeling, a PAH model was developed, and T0901317, an agonist of LXR, was used to examine the effect of LXR activation. PAH rats demonstrated obvious cardiac hypertrophy and remodeling in the right ventricle, but significant improvement of cardiac hypertrophy and remodeling was observed in PAH rats treated with T0901317. Through RT-PCR, Western blot and ELISA examination, NF-κB, IL-6, TNF-α, and iNOS were found to be significantly reduced in PAH rats treated with T0901317 compared to PAH rats treated with DMSO. Apoptosis was also significantly reduced in PAH rats treated with T0901317. Thus, LXR activation may inhibit PAH-induced cardiac hypertrophy and remodeling by inhibiting NF-κB-mediated inflammatory pathways.

Photoswitchable Spiropyran Dyads for Biological Imaging.

The synthesis of a small-molecule dyad consisting of a far-red-emitting silicon rhodamine dye that is covalently linked to a photochromic spironaphthothiopyran unit, which serves as a photoswitchable quencher, is reported. This system can be switched reversibly between the fluorescent and nonfluorescent states using visible light at wavelengths of 405 and 630 nm, respectively, and it works effectively in aqueous solution. Live-cell imaging demonstrates that this dyad has several desirable features, including excellent membrane permeability, fast and reversible modulation of fluorescence by visible light, and good contrast between the bright and dark states.