Treatment for locally resectable stage IIIC1r cervical cancer: surgery or chemoradiotherapy?

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.

Transcriptomic and Proteomic Landscape of Sugarcane Response to Biotic and Abiotic Stressors.

Sugarcane, a C4 plant, provides most of the world's sugar, and a substantial amount of renewable bioenergy, due to its unique sugar-accumulating and feedstock properties. Brazil, India, China, and Thailand are the four largest sugarcane producers worldwide, and the crop has the potential to be grown in arid and semi-arid regions if its stress tolerance can be improved. Modern sugarcane cultivars which exhibit a greater extent of polyploidy and agronomically important traits, such as high sugar concentration, biomass production, and stress tolerance, are regulated by complex mechanisms. Molecular techniques have revolutionized our understanding of the interactions between genes, proteins, and metabolites, and have aided in the identification of the key regulators of diverse traits. This review discusses various molecular techniques for dissecting the mechanisms underlying the sugarcane response to biotic and abiotic stresses. The comprehensive characterization of sugarcane's response to various stresses will provide targets and resources for sugarcane crop improvement.

[Comprehensive nursing intervention for advanced prostate cancer patients undergoing chemoradiotherapy].

OBJECTIVE: To explore the effect of comprehensive nursing intervention in advanced PCa patients receiving chemoradiotherapy. METHODS: This study included 70 patients with advanced PCa undergoing chemoradiotherapy in our department from January 2020 to April 2022, who were randomly divided into a control (n = 35) and an intervention group (n = 35), the former receiving routine nursing care while the latter comprehensive nursing intervention, including such measures as health education, psychological care, radiotherapy care, chemotherapy care, and complication care. After intervention, comparisons were made between the two groups of patients in the Expanded Prostate Cancer Index Composite (EPIC) scores and incidence of adverse reactions to chemoradiotherapy. RESULTS: The scores on all the dimensions of EPIC were significantly higher in the intervention than in the control group (P < 0.05) and the incidence rate of radiation-induced proctitis and cystitis remarkably lower in the former than in the latter (36.11% vs 71.43%, P < 0.05). CONCLUSION: Comprehensive nursing intervention can improve the quality of life of the PCa patients undergoing chemoradiotherapy, increase their compliance with treatment and reduce their adverse reactions, and therefore deserves clinical promotion.

[Application of IMCHB based nursing model in self-efficacy and negative emotion of prostate cancer radiotherapy patients].

OBJECTIVE: To study the impact of the nursing model based on the interactive model of health behavior (IMCHB) on the self-efficacy and negative emotions of prostate cancer patients. METHODS: 70 cases clinically admitted to our hospital from January 1, 2021 to January 31, 2023 Patients who received radiotherapy for prostate cancer were taken as research subjects and divided into a control group (n=35) and an observation group (n=35) according to the random drawing method. The control group was given routine care, and the observation group was given a nursing model based on IMCHB on the basis of the control group. Compare the incidence of complications between the two groups, and use the Frankl Compliance Scale (FCS) to compare the compliance behaviors of the two groups, negative emotions on the day of admission and 1 day before discharge were statistically compared between the two groups Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and self-management efficacy General Self-Efficacy Scale (GSES)and quality of life World Health Organization Quality of Life Scale Short Form (WHOQOL-BREF). RESULTS: The incidence of radiation proctitis and radiation cystitis in observation group was lower than that in control group, the difference was statistically significant (P<0.05).The total compliance rate of medical compliance was 97.83%, which was higher than that of the control group, 84.78%, and the difference was statistically significant (P<0.05); 1 day before discharge, the HAMD and HAMA scores of the observation group were lower than those of the control group, GSES, and WHOQOL-BREF The score was higher than that of the control group, and the difference was statistically significant (P<0.05). CONCLUSION: The IMCHB nursing model can improve self-management efficiency and alleviate negative emotions when applied to patients undergoing radiotherapy for prostate cancer.

Proteomics data analysis using multiple statistical approaches identified proteins and metabolic networks associated with sucrose accumulation in sugarcane.

BACKGROUND: Sugarcane is the most important sugar crop, contributing > 80% of global sugar production. High sucrose content is a key target of sugarcane breeding, yet sucrose improvement in sugarcane remains extremely slow for decades. Molecular breeding has the potential to break through the genetic bottleneck of sucrose improvement. Dissecting the molecular mechanism(s) and identifying the key genetic elements controlling sucrose accumulation will accelerate sucrose improvement by molecular breeding. In our previous work, a proteomics dataset based on 12 independent samples from high- and low-sugar genotypes treated with ethephon or water was established. However, in that study, employing conventional analysis, only 25 proteins involved in sugar metabolism were identified . RESULTS: In this work, the proteomics dataset used in our previous study was reanalyzed by three different statistical approaches, which include a logistic marginal regression, a penalized multiple logistic regression named Elastic net, as well as a Bayesian multiple logistic regression method named Stochastic search variable selection (SSVS) to identify more sugar metabolism-associated proteins. A total of 507 differentially abundant proteins (DAPs) were identified from this dataset, with 5 of them were validated by western blot. Among the DAPs, 49 proteins were found to participate in sugar metabolism-related processes including photosynthesis, carbon fixation as well as carbon, amino sugar, nucleotide sugar, starch and sucrose metabolism. Based on our studies, a putative network of key proteins regulating sucrose accumulation in sugarcane is proposed, with glucose-6-phosphate isomerase, 2-phospho-D-glycerate hydrolyase, malate dehydrogenase and phospho-glycerate kinase, as hub proteins. CONCLUSIONS: The sugar metabolism-related proteins identified in this work are potential candidates for sucrose improvement by molecular breeding. Further, this work provides an alternative solution for omics data processing.

La@[La5&B30]0/-/2-: endohedral trihedral metallo-borospherenes with spherical aromaticity.

It is well-known that transition-metal-doping induces dramatic changes in the structures and bonding of small boron clusters, as demonstrated by the newly observed perfect inverse sandwich D8h [La(η8-B8)La] and D9h [La(η9-B9)La]-. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the possibility of perfect endohedral trihedral metallo-borospherene D3h La@[La5&B30] (1, 3A'1) and its monoanion Cs La@[La5&B30]- (2, 2A') and dianion D3h La@[La5&B30]2- (3, 1A'1). These La-doped boron clusters are composed of three inverse sandwich La(η8-B8)La on the waist and two inverse sandwich La(η9-B9)La on the top and bottom which share one apex La atom at the center and six periphery B2 units between neighboring η8-B8 and η9-B9 rings, with three octo-coordinate La atoms and two nona-coordinate La atoms as integrated parts of the cage surface. Detailed adaptive natural density partitioning (AdNDP) and iso-chemical shielding surface (ICSS) analyses indicate that La@[La5&B30]0/-/2- (1/2/3) are spherically aromatic in nature. The one-dimensional nanowire La4B21 (4, P31m) constructed from D3h La@[La5&B30] (1) along the C3 axis of the system appears to be metallic. The IR and Raman spectra of La@[La5&B30] (1) and photoelectron spectroscopy of the slightly distorted Cs La@[La5&B30]- (2) are theoretically simulated to facilitate their spectroscopic characterizations.

Stereotactic body radiotherapy for recurrent and oligometastatic soft tissue sarcoma.

BACKGROUND: Soft tissue sarcoma (STS) is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biological pattern and clinical transformation with localized invasive growth and is susceptible to hematogenous metastasis. Local therapeutic strategies may treat recurrent and oligometastatic STS, including surgery and radiation therapy. This study aimed to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for recurrent and oligometastatic STS. METHODS: We retrospectively analyzed 37 recurrent and oligometastatic STS patients with 58 lesions treated with SBRT from 2009 to 2019 at our institution. Oligometastatic is defined as metastatic lesions less than or equal to 3. The primary endpoint was local control (LC); secondary endpoints were survival and toxicity. RESULTS: The median follow-up was 21.0 months (3.0 to 125.0 months). Among 37 patients, 18 were recurrent patients, and 19 were oligometastatic patients. Median LC was 25.0 months (95% CI 20.0-45.0). The 1-, 2-, and 3-year LC rates were 80.2%, 58.3%, and 46.6%, respectively. Median overall survival (OS) was 24.0 months (95% CI 13.0-28.0), and the survival rates after SBRT were 71.5%, 40.0%, and 29.1% at 1, 2, and 3-year, respectively. Median progression-free survival (PFS) was 10.0 months (95% CI 8.0-15.0 months), PFS rate after SBRT was 43.6%, 26.8%, and 18.4% at 1, 2, and 3 years, respectively. Late grade 3 radiation dermatitis was observed in one patient (2.7%). Using univariate and multivariate COX analysis, better OS, PFS, and LC were obtained in the histologic grade 1(G1) group, and tumor size and a number of lesions influenced LC. CONCLUSIONS: SBRT is a safe and effective treatment for patients with recurrent and oligometastatic STS. Histological grade influences local control and survival. SBRT may be a promising treatment option for recurrent and oligometastatic STS.

Integrated Transcriptome and Metabolome Analysis to Identify Sugarcane Gene Defense against Fall Armyworm (Spodoptera frugiperda) Herbivory.

Sugarcane is the most important sugar crop, contributing ≥80% to total sugar production around the world. Spodoptera frugiperda is one of the main pests of sugarcane, potentially causing severe yield and sugar loss. The identification of key defense factors against S. frugiperda herbivory can provide targets for improving sugarcane resistance to insect pests by molecular breeding. In this work, we used one of the main sugarcane pests, S. frugiperda, as the tested insect to attack sugarcane. Integrated transcriptome and metabolomic analyses were performed to explore the changes in gene expression and metabolic processes that occurred in sugarcane leaf after continuous herbivory by S. frugiperda larvae for 72 h. The transcriptome analysis demonstrated that sugarcane pest herbivory enhanced several herbivory-induced responses, including carbohydrate metabolism, secondary metabolites and amino acid metabolism, plant hormone signaling transduction, pathogen responses, and transcription factors. Further metabolome analysis verified the inducement of specific metabolites of amino acids and secondary metabolites by insect herbivory. Finally, association analysis of the transcriptome and metabolome by the Pearson correlation coefficient method brought into focus the target defense genes against insect herbivory in sugarcane. These genes include amidase and lipoxygenase in amino acid metabolism, peroxidase in phenylpropanoid biosynthesis, and pathogenesis-related protein 1 in plant hormone signal transduction. A putative regulatory model was proposed to illustrate the sugarcane defense mechanism against insect attack. This work will accelerate the dissection of the mechanism underlying insect herbivory in sugarcane and provide targets for improving sugarcane variety resistance to insect herbivory by molecular breeding.

Cold-Induced Physiological and Biochemical Alternations and Proteomic Insight into the Response of Saccharum spontaneum to Low Temperature.

Sugarcane, a cash crop, is easily affected by low temperature, which results in a decrease in yield and sugar production. Breeding a new variety with cold tolerance is an essential strategy to reduce loss from cold stress. The identification of germplasms and genes/proteins with cold tolerance is a vital step in breeding sugarcane varieties with cold tolerance via a conventional program and molecular technology. In this study, the physiological and biochemical indices of 22 genotypes of S. spontaneum were measured, and the membership function analysis method was used to comprehensively evaluate the cold tolerance ability of these genotypes. The physiological and biochemical indices of these S. spontaneum genotypes showed a sophisticated response to low temperature. On the basis of the physiological and chemical indices, the genotypes were classified into different cold tolerance groups. Then, the high-tolerance genotype 1027 and the low-tolerance genotype 3217 were selected for DIA-based proteomic analysis by subjecting them to low temperature. From the four comparison groups, 1123, 1341, 751, and 1693 differentially abundant proteins (DAPs) were identified, respectively. The DAPs based on genotypes or treatments participated in distinct metabolic pathways. Through detailed analysis of the DAPs, some proteins related to protein homeostasis, carbohydrate and energy metabolism, amino acid transport and metabolism, signal transduction, and the cytoskeleton may be involved in sugarcane tolerance to cold stress. Furthermore, five important proteins related to cold tolerance were discovered for the first time in this study. This work not only provides the germplasms and candidate target proteins for breeding sugarcane varieties with cold tolerance via a conventional program and molecular breeding, but also helps to accelerate the determination of the molecular mechanism underlying cold tolerance in sugarcane.

[Cyberknife stereotactic body radiotherapy for liver metastases from prostate cancer].

OBJECTIVE: To investigate the effectiveness and adverse effects of Cyberknife stereotactic body radiotherapy (SBRT) on liver metastases from PCa. METHODS: From June 2009 to September 2016, we treated 20 cases of PCa liver metastases by Cyberknife SBRT, at a total dose of 36 (30－50) Gy, on 1－3 liver metastatic lesions, for 3－5 times, with a prescription isodose line of 70－92%. We assessed the therapeutic effect according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), calculated the survival and disease-control rates using the Kaplan-Meier method, and analyzed the adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events－Version 4.0 (CTCAE 4.0). RESULTS: Of all the cases treated, complete response (CR) was found in 8 (40.0%), partial response (PR) in 9 (45.0%), stable disease (SD) in 2 (10.0%), and progressive disease (PD) in 1 (5.0%), with a local control rate (CR+PR) of 85.0% and a disease-control rate (CR+PR+SD) of 95.0%. Among the 14 patients with elevated PSA, 10 (71.4%) showed a significant decrease after treatment. The median follow-up time was 17 months, the 1- and 2-year survival rates were 85.0% and 15.0%, respectively, and the median survival time of the 20 patients was 16.5 months (95% CI: 12.12－22.88). Cyberknife SBRT was well tolerated in all the patients, with only a few mild adverse events (mainly grades 1 and 2 but no 4 and 5) during the whole course of treatment. CONCLUSIONS: Cyberknife SBRT is safe and effective in the treatment of PCa liver metastases, with a high local control rate, and capable of reducing the PSA level and raising the long-term survival rate of the patients.

[Nursing care of prostate cancer patients against radiative proctitisinduced by CyberKnife treatment].

OBJECTIVE: To investigate the nursing care of prostate cancer (PCa) patients againstradioactive proctitisinduced byCyberKnifetreatment. METHODS: Sixty-eightPCapatients undergoingCyberKnife treatment in the observation group receivedspecialnursing care againstradioactive proctitis. The nursing measures includedthoserelevant toCyberKnife treatment, prevention ofradioactive proctitis, skin care, and discharge guidance. Meanwhile, another 54 prostate cancer patients received traditional nursing care as controls. We compared the incidence rate and severity of radioactive proctitis between the two groups of patients. RESULTS: The incidence rate of radioactive proctitiswas markedly lower in the observation group than in the control (2.9% vs 13.0%, P<0.05), but no statistically significant difference was observed in the severity of radioactive proctitis between the two groups of patients. CONCLUSIONS: The special nursing care againstCyberKnife-induced radioactiveproctitiscan significantlyreduce the incidence of radioactive proctitis andimprove the effect of CyberKnife treatment of prostate cancer, which therefore deserves wide clinical application.

Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl- secretion in human colonic T84 cells.

Bile acids are known to initiate intricate signaling events in a variety of tissues, primarily in the liver and gastrointestinal tract. Of the known bile acids, only the 7α-dihydroxy species, deoxycholic acid and chenodeoxycholic acid (CDCA), and their conjugates, activate processes that stimulate epithelial Cl- secretion. We have previously published that CDCA acts in a rapid manner to stimulate colonic ion secretion via protein kinase A (PKA)-mediated activation of the dominant Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) (Ao M, Sarathy J, Domingue J, Alrefai WA, and Rao MC. Am J Physiol Cell Physiol 305: C447-C456, 2013); however, PKA signaling did not account for the entire CDCA response. Here we show that in human colonic T84 cells, CDCA's induction of CFTR activity, measured as changes in short-circuit current (Isc), is dependent on epidermal growth factor receptor (EGFR) activation and does not involve the bile acid receptors TGR5 or farnesoid X receptor. CDCA activation of Cl- secretion does not require Src, mitogen-activated protein kinases, or phosphoinositide 3-kinase downstream of EGFR but does require an increase in cytosolic Ca2+ In addition to PKA signaling, we found that the CDCA response requires the novel involvement of the exchange protein directly activated by cAMP (EPAC). EPAC is a known hub for cAMP and Ca2+ cross talk. Downstream of EPAC, CDCA activates Rap2, and changes in free cytosolic Ca2+ were dependent on both EPAC and EGFR activation. This study establishes the complexity of CDCA signaling in the colonic epithelium and shows the contribution of EGFR, EPAC, and Ca2+ in CDCA-induced activation of CFTR-dependent Cl- secretion.

Lithocholic acid attenuates cAMP-dependent Cl- secretion in human colonic epithelial T84 cells.

Bile acids (BAs) play a complex role in colonic fluid secretion. We showed that dihydroxy BAs, but not the monohydroxy BA lithocholic acid (LCA), stimulate Cl(-) secretion in human colonic T84 cells (Ao M, Sarathy J, Domingue J, Alrefai WA, Rao MC. Am J Physiol Cell Physiol 305: C447-C456, 2013). In this study, we explored the effect of LCA on the action of other secretagogues in T84 cells. While LCA (50 µM, 15 min) drastically (>90%) inhibited FSK-stimulated short-circuit current (Isc), it did not alter carbachol-stimulated Isc LCA did not alter basal Isc, transepithelial resistance, cell viability, or cytotoxicity. LCA's inhibitory effect was dose dependent, acted faster from the apical membrane, rapid, and not immediately reversible. LCA also prevented the Isc stimulated by the cAMP-dependent secretagogues 8-bromo-cAMP, lubiprostone, or chenodeoxycholic acid (CDCA). The LCA inhibitory effect was BA specific, since CDCA, cholic acid, or taurodeoxycholic acid did not alter FSK or carbachol action. While LCA alone had no effect on intracellular cAMP concentration ([cAMP]i), it decreased FSK-stimulated [cAMP]i by 90%. Although LCA caused a small increase in intracellular Ca(2+) concentration ([Ca(2+)]i), chelation by BAPTA-AM did not reverse LCA's effect on Isc LCA action does not appear to involve known BA receptors, farnesoid X receptor, vitamin D receptor, muscarinic acetylcholine receptor M3, or bile acid-specific transmembrane G protein-coupled receptor 5. LCA significantly increased ERK1/2 phosphorylation, which was completely abolished by the MEK inhibitor PD-98059. Surprisingly PD-98059 did not reverse LCA's effect on Isc Finally, although LCA had no effect on basal Isc, nystatin permeabilization studies showed that LCA both stimulates an apical cystic fibrosis transmembrane conductance regulator Cl(-) current and inhibits a basolateral K(+) current. In summary, 50 µM LCA greatly inhibits cAMP-stimulated Cl(-) secretion, making low doses of LCA of potential therapeutic interest for diarrheal diseases.

Selenobacteria-mediated Se transformation and uptake involving the unique genetic code.

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.

PERK inhibitor (ISRIB) improves depression-like behavior by inhibitions of HPA-axis over-activation in mice exposed to chronic restraint stress.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells.

High levels of chenodeoxycholic acid (CDCA) and deoxycholic acid stimulate Cl(-) secretion in mammalian colonic epithelia. While different second messengers have been implicated in this action, the specific signaling pathway has not been fully delineated. Using human colon carcinoma T84 cells, we elucidated this cascade assessing Cl(-) transport by measuring I(-) efflux and short-circuit current (Isc). CDCA (500 µM) rapidly increases I(-) efflux, and we confirmed by Isc that it elicits a larger response when added to the basolateral vs. apical surface. However, preincubation with cytokines increases the monolayer responsiveness to apical addition by 55%. Nystatin permeabilization studies demonstrate that CDCA stimulates an eletrogenic apical Cl(-) but not a basolateral K(+) current. Furthermore, CDCA-induced Isc was inhibited (≥67%) by bumetanide, BaCl2, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. CDCA-stimulated Isc was decreased 43% by the adenylate cyclase inhibitor MDL12330A and CDCA increases intracellular cAMP concentration. The protein kinase A inhibitor H89 and the microtubule disrupting agent nocodazole, respectively, cause 94 and 47% reductions in CDCA-stimulated Isc. Immunoprecipitation with CFTR antibodies, followed by sequential immunoblotting with Pan-phospho and CFTR antibodies, shows that CDCA increases CFTR phosphorylation by approximately twofold. The rapidity and side specificity of the response to CDCA imply a membrane-mediated process. While CDCA effects are not blocked by the muscarinic receptor antagonist atropine, T84 cells possess transcript and protein for the bile acid G protein-coupled receptor TGR5. These results demonstrate for the first time that CDCA activates CFTR via a cAMP-PKA pathway involving microtubules and imply that this occurs via a basolateral membrane receptor.

Novel triazole-based fluorescent probes for Pd2+ in aqueous solutions: design, theoretical calculations and imaging.

The first triazole-containing fluorescent probe with excellent water-solubility for Pd(2+) was presented. The results indicated that an amide-triazole-amide binding sequence was responsible for the unique affinity of PS-1 toward Pd(2+). Among the tested metal ions, only Pd(2+) could selectively quench the fluorescence of PS-1 under physiological conditions, while other common interference ions like Pt(2+) and Ru(3+) caused little changes. The successful fluorescence imaging of Pd(2+) in HeLa cells implied the potential applications of PS-1 in biological Pd(2+)-analysis.

A BINOL-based ratiometric fluorescent sensor for Zn2+ and in situ generated ensemble for selective recognition of histidine in aqueous solution.

A novel BINOL-based ratiometric fluorescent sensor (R2) is presented, which can selectively respond to Zn(2+) over Cd(2+) and other metal ions with fluorescence enhancement in aqueous solution. The R2 was successfully applied in the imaging of Zn(2+) in living cells. Additionally, the in situ generated R2-Zn(II) ensemble could further serve as a probe to distinguish histidine from other amino acids via a displacement mode.

Perfect cubic metallo-borospherenes TM8B6 (TM = Ni, Pd, Pt) as superatoms following the 18-electron rule.

Transition-metal (TM)-doped metallo-borospherenes exhibit unique structures and bonding in chemistry which have received considerable attention in recent years. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the first and smallest perfect cubic metallo-borospherenes Oh TM8B6 (TM = Ni (1), Pd (2), Pt (3)) and Oh Ni8B6- (1-) which contain eight equivalent TM atoms at the vertexes of a cube and six quasi-planar tetra-coordinate face-capping boron atoms on the surface. Detailed canonical molecular orbital and adaptive natural density partitioning bonding analyses indicate that Oh TM8B6 (1/2/3) as superatoms possess nine completely delocalized 14c-2e bonds following the 18-electron principle (1S21P61D10), rendering spherical aromaticity and extra stability to the complex systems. Furthermore, Ni8B6 (1) can be used as building blocks to form the three-dimensional metallic binary crystal NiB (4) (Pm3̄m) in a bottom-up approach which possesses a typical CsCl-type structure with an octa-coordinate B atom located exactly at the center of the cubic unit cell. The IR, Raman, UV-vis and photoelectron spectra of the concerned clusters are computationally simulated to facilitate their experimental characterization.

Heptacoordinate transition-metal-decorated metallo-borospherenes and multiple-helix metallo-boronanotubes.

The recent discovery of lanthanide-metal-decorated metallo-borospherenes LM3B18- (LM = La, Tb) marks the onset of a new class of boron-metal binary nanomaterials. Using the experimentally observed or theoretically predicted borospherenes as ligands and based on extensive first-principles theory calculations, we predict herein a series of novel chiral metallo-borospherenes C2 Ni6 ∈ B39- (1), C1 Ni6 ∈ B41+ (3), C2 Ni6 ∈ B422+ (4), C2 Ni6 ∈ B42 (5), and C2 Ni8 ∈ B56 (6) as the global minima of the systems decorated with quasi-planar heptacoordinate Ni (phNi) centers in η7-B7 heptagons on the cage surfaces, which are found to be obviously better favoured in coordination energies than hexacoordinate Ni centers in previously reported D2d Ni6 ∈ B40 (2). Detailed bonding analyses indicate that these phNi-decorated metallo-borospherenes follow the σ + π double delocalization bonding pattern, with two effective (d-p)σ coordination bonds formed between each phNi and its η7-B7 ligand, rendering spherical aromaticity and extra stability to the systems. The structural motif in elongated axially chiral Ni6 ∈ B422+ (4), Ni6 ∈ B42 (5), and Ni8 ∈ B56 (6) can be extended to form the metallic phNi-decorated boron double chain (BDC) double-helix Ni4 ∈ B28 (2, 0) (P4̄m2) (8), triple-helix Ni6 ∈ B42 (3, 0) (P3̄m1) (9), and quadruple-helix Ni8 ∈ B56 (4, 0) (P4mm) (10) metallo-boronanotubes, which can be viewed as quasi-multiple-helix DNAs composed of interconnected BDCs decorated with phNi centers in η7-B7 heptagons on the tube surfaces in the atomic ratio of Ni : B = 1 : 7.