Radiopharmaceuticals Targeting Gastrin-Releasing Peptide Receptor for Diagnosis and Therapy of Prostate Cancer.

The high incidence and heavy disease burden of prostate cancer (PC) require accurate and comprehensive assessment for appropriate disease management. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cannot detect PSMA-negative lesions, despite its key role in PC disease management. The overexpression of gastrin-releasing peptide receptor (GRPR) in PC lesions reportedly performs as a complementary target for the diagnosis and therapy of PC. Radiopharmaceuticals derived from the natural ligands of GRPR have been developed. These radiopharmaceuticals enable the visualization and quantification of GRPR within the body, which can be used for disease assessment and therapeutic guidance. Recently developed radiopharmaceuticals exhibit improved pharmacokinetic parameters without deterioration in affinity. Several heterodimers targeting GRPR have been constructed as alternatives because of their potential to detect tumor lesions with a low diagnostic efficiency of single target detection. Moreover, some GRPR-targeted radiopharmaceuticals have entered clinical trials for the initial staging or biochemical recurrence detection of PC to guide disease stratification and therapy, indicating considerable potential in PC disease management. Herein, we comprehensively summarize the progress of radiopharmaceuticals targeting GRPR. In particular, we discuss the impact of ligands, chelators, and linkers on the distribution of radiopharmaceuticals. Furthermore, we summarize a potential design scheme to facilitate the advancement of radiopharmaceuticals and, thus, prompt clinical translation.

[The Extract from Punica Granatum (Pomegranate) Leaves Promotes Apoptosis and Impairs Metastasis in Prostate Cancer Cells].

OBJECTIVE: To investigate the effects of pomegranate leaves extract(PLE)on proliferation,apoptosis and metastasis of prostate cancer cells. METHODS: The proliferation of TRAMP-C1,DU145,PC3 prostate cancer cells treated with different concentrations of PLE (final mass concentrations were 12.5,25,50,100, 200 µg/mL,respectively) for different time (24,48,72 h) was detected by MTT assay. Colony formation assay was performed to verify the long-term effects of PLE on the proliferation of DU145 and PC3 cells.After being treated with PLE for 48 h,Hoechst-33258 staining was used to observe the changes in the nucleus,the cell apoptotic rate was detected by flow cytometry,and wound-healing migration assay was perform to test the change of migration. RESULTS: In comparison with the control group,PLE in the range of 12.5-200 µg/mL had a certain inhibitory effect on the proliferation of TRAMP-C1,DU145 and PC3 cells ( P<0.05).In the range of 6.25-100 µg/mL,the number of colony formation of DU145 and PC3 was significantly reduced( P<0.01).After PLE treated for 48 h, the apoptotic features of nuclear fragmentation and the formation apoptotic body was observed in PC3. With the increase of concentration,the apoptotic rate increased gradually ( P<0.05),and the ability of cells to migrate to the scratch area was significantly weaker than the control group ( P<0.01). CONCLUSION: PLE has effect on proliferation,apoptosis and metastasis of prostate cancer cells.

Expressions of miR-22 and miR-135a in acute pancreatitis.

This study examined the expressions of miR-22 and miR-135a in rats with acute edematous pancreatitis (AEP) and their target genes in order to shed light on the involvement of miR-22 and miR-135a in the pathogenesis of acute pancreatitis (AP). The in vivo model of AEP was established by introperitoneal injection of L-arginine (150 mg/kg) in rats. The miRNA microarray analysis was used to detect the differential expression of miRNAs in pancreatic tissue in AEP and normal rats. The in vitro AEP model was established by inducing the rat pancreatic acinar cell line (AR42J) with 50 ng/mL recombinant rat TNF-α. Real-time quantitative RT-PCR was employed to detect the expression of miR-22 and miR-135a in AR42J cells. Lentiviruses carrying the miRNA mimic and anti-miRNA oligonucleotide (AMO) of miR-22 and miR-135a were transfected into the AR42J cells. The AR42J cells transfected with vehicle served as control. Western blotting was used to measure the expression of activated caspase3 and flow cytometry analysis to detect the apoptosis of AR42J cells. Targets of miR-22 and miR-135a were predicted by using TargetScan, miRanda, and TarBase. Luciferase reporter assay and quantitative real-time RT-PCR were performed to confirm whether ErbB3 and Ptk2 were the target gene of miR-22 and miR-135a, respectively. The results showed that the expression levels of miR-22 and miR-135a were obviously increased in AEP group compared with the control group in in-vivo and in-vitro models. The expression levels of miR-22 and miR-135a were elevated conspicuously and the expression levels of their target genes were reduced significantly in AR42J cells transfected with lentiviruses carrying the miRNA mimic. The apoptosis rate was much higher in the TNF-α-induced cells than in non-treated cells. The AR42J cells transfected with miRNA AMOs expressed lower level of miR-22 and miR-135a and had lower apoptosis rate, but the expression levels of ErbB3 and Ptk2 were increased obviously. It was concluded that the expression levels of miR-22 and miR-135a were elevated in AEP. Up-regulating the expression of miR-22 and miR-135a may promote the apoptosis of pancreatic acinar cells by repressing ErbB3 and Ptk2 expression in AEP.

A Novel HPLC Method for Quality Inspection of NRK Biosynthesized ß-Nicotinamide Mononucleotide.

ß-nicotinamide mononucleotide (NMN) has a good effect on delaying aging, repairing DNA and ameliorating metabolic disease. Biosynthesis with nicotinamide riboside kinase (NRK) takes a large part in NMN manufacture, but there is no available NMN quality standard and analytical method at present. In this study, we developed a specific high-performance liquid chromatography method for the assessment of NMN-related substances, including NMN and its potential impurities from NRK biological production and storage. Forced degradation study was performed under acid, base, oxidative, photolytic and thermal conditions. The separation of related substances was achieved on an Elite Hypersil ODS column using phosphate buffer-methanol gradient at a flow rate of 1.0 mL/min. The detection wavelength was maintained at 260 nm. The resolutions among all related substances were better than 1.5. Significant degradation was observed in basic and thermal conditions. All related substances showed good linearity with a coefficient of determination (R2) higher than 0.999. The accuracy values of all related substances were between 91.2% and 108.6%. Therefore, the validated analytical method is appropriate for inspecting the quality of NMN in its NRK biosynthetic manufacture and storage, thus further helping to unify NMN quality standards and facilitate related studies on NMN.

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment.

Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo. Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice. Results: In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3 mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin. Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.

Selective degradation of hyperphosphorylated tau by proteolysis-targeting chimeras ameliorates cognitive function in Alzheimer's disease model mice.

Alzheimer's disease (AD) is one of the most common chronic neurodegenerative diseases. Hyperphosphorylated tau plays an indispensable role in neuronal dysfunction and synaptic damage in AD. Proteolysis-targeting chimeras (PROTACs) are a novel type of chimeric molecule that can degrade target proteins by inducing their polyubiquitination. This approach has shown promise for reducing tau protein levels, which is a potential therapeutic target for AD. Compared with traditional drug therapies, the use of PROTACs to reduce tau levels may offer a more specific and efficient strategy for treating AD, with fewer side effects. In the present study, we designed and synthesized a series of small-molecule PROTACs to knock down tau protein. Of these, compound C8 was able to lower both total and phosphorylated tau levels in HEK293 cells with stable expression of wild-type full-length human tau (termed HEK293-htau) and htau-overexpressed mice. Western blot findings indicated that C8 degraded tau protein through the ubiquitin-proteasome system in a time-dependent manner. In htau-overexpressed mice, the results of both the novel object recognition and Morris water maze tests revealed that C8 markedly improved cognitive function. Together, our findings suggest that the use of the small-molecule PROTAC C8 to degrade phosphorylated tau may be a promising therapeutic strategy for AD.

Discovery of orally bioavailable ALK PROTACs based ceritinib against ALK positive cancers.

Anaplastic lymphoma kinase (ALK) fusion genes promote a variety of human malignancies. Although several ALK inhibitors have significantly improved disease prognosis in patients with ALK positive cancers, the persistent emergence of acquired drug-resistant mutations remain the major problem in clinic treatment. Adoption of new therapeutic strategies such as proteolysis targeting chimera (PROTAC) to overcome drug resistance in BTK/AR-related cancers have shown promising prospect. Herein, we reported the integrate ALK PROTACs through overall optimization of linker, revealed that subtle structural differences can lead to significant activity difference, indicating the key role of conformation of PROTACs in inducing the formation of E3-PROTAC-target protein ternary complexes. A series of rigid ALK PROTACs were developed through conjugation of Ceritinib and thalidomide, orally bioavailable PROTAC 4B (F = 14.22 %) was obtained by overall optimization of molecular properties. 4B effectively induced long lasting degradation of ALK fusion proteins and strong repression of downstream pathway in Karpas 299 cells (DC50 = 119.33 nM, Dmax = 97.1 %) and showed comparable anti-proliferative activity to Ceritinib (IC50 = 3.11 ± 0.08 nM vs IC50 = 1.31 ± 0.43 nM). Furthermore, 4B significantly inhibited the growth of Karpas 299 xenografts in vivo with TGI of 49.5 % and showed superior anti-proliferative activity against G1202R mutation to Ceritinib (IC50 = 52.82 nM vs IC50 = 109.5 nM). Overall, 4B is expected to be a potential treatment for ALK-driven malignancies.

CT colonography: external clinical validation of an algorithm for computer-assisted prone and supine registration.

PURPOSE: To perform external validation of a computer-assisted registration algorithm for prone and supine computed tomographic (CT) colonography and to compare the results with those of an existing centerline method. MATERIALS AND METHODS: All contributing centers had institutional review board approval; participants provided informed consent. A validation sample of CT colonographic examinations of 51 patients with 68 polyps (6-55 mm) was selected from a publicly available, HIPAA compliant, anonymized archive. No patients were excluded because of poor preparation or inadequate distension. Corresponding prone and supine polyp coordinates were recorded, and endoluminal surfaces were registered automatically by using a computer algorithm. Two observers independently scored three-dimensional endoluminal polyp registration success. Results were compared with those obtained by using the normalized distance along the colonic centerline (NDACC) method. Pairwise Wilcoxon signed rank tests were used to compare gross registration error and McNemar tests were used to compare polyp conspicuity. RESULTS: Registration was possible in all 51 patients, and 136 paired polyp coordinates were generated (68 polyps) to test the algorithm. Overall mean three-dimensional polyp registration error (mean ± standard deviation, 19.9 mm ± 20.4) was significantly less than that for the NDACC method (mean, 27.4 mm ± 15.1; P = .001). Accuracy was unaffected by colonic segment (P = .76) or luminal collapse (P = .066). During endoluminal review by two observers (272 matching tasks, 68 polyps, prone to supine and supine to prone coordinates), 223 (82%) polyp matches were visible (120° field of view) compared with just 129 (47%) when the NDACC method was used (P < .001). By using multiplanar visualization, 48 (70%) polyps were visible after scrolling ± 15 mm in any multiplanar axis compared with 16 (24%) for NDACC (P < .001). CONCLUSION: Computer-assisted registration is more accurate than the NDACC method for mapping the endoluminal surface and matching the location of polyps in corresponding prone and supine CT colonographic acquisitions.

Achieving nitrogen removal with low material and energy consumption through partial nitrification coupled with short-cut sulfur autotrophic denitrification in a single-stage SBR.

An innovative partial nitrification and short-cut sulfur autotrophic denitrification (PN-SSAD, NH4+-N â†’ NO2--N â†’ N2) coupled system in a single-stage SBR was proposed to treat low C/N wastewater with low material and energy consumption. Nearly 50 % alkalinity consumption and 40 % sulfate production were reduced in S0-SSAD compared with S0-SAD, whereas the autotrophic denitrification rate was increased by 65 %. In S0-PN-SSAD, the TN removal efficiency reached almost 99 % without additional organic carbon. Furthermore, pyrite (FeS2) rather than S0 served as the electron donor to optimize the PN-SSAD process. The practical sulfate production in S0-PN-SSAD and FeS2-PN-SSAD were about 38 % and 52 % lower than complete nitrification and sulfur autotrophic denitrification (CN-SAD), respectively. Thiobacillus was the major autotrophic denitrification bacteria in S0-PN-SSAD (34.47 %) and FeS2-PN-SSAD (14.88 %). Nitrosomonas and Thiobacillus played a synergistic effect in the coupled system. FeS2-PN-SSAD is expected as an alternative technology for nitrification and heterotrophic denitrification (HD) in treating low C/N wastewater.

Dysregulation of histone modifications in bone marrow mesenchymal stem cells during skeletal ageing: roles and therapeutic prospects.

Age-associated bone diseases such as osteoporosis (OP) are common in the elderly due to skeletal ageing. The process of skeletal ageing can be accelerated by reduced proliferation and osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs). Senescence of BM-MSCs is a main driver of age-associated bone diseases, and the fate of BM-MSCs is tightly regulated by histone modifications, such as methylation and acetylation. Dysregulation of histone modifications in BM-MSCs may activate the genes related to the pathogenesis of skeletal ageing and age-associated bone diseases. Here we summarize the histone methylation and acetylation marks and their regulatory enzymes that affect BM-MSC self-renewal, differentiation and senescence. This review not only describes the critical roles of histone marks in modulating BM-MSC functions, but also underlines the potential of epigenetic enzymes as targets for treating age-associated bone diseases. In the future, more effective therapeutic approaches based on these epigenetic targets will be developed and will benefit elderly individuals with bone diseases, such as OP.

A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Is air pollution detrimental to regional innovation? An empirical heterogeneity test based on Chinese cities.

Nowadays, innovation seems to be the inevitable choice to achieve stable economic growth. However, the negative impact of air pollution on health and economy makes air pollution an important factor in regional innovation, which deserves our discussion. The overall regional innovation level from 2014 to 2019 has an upward trend, while the overall air pollution has a downward trend during the period, which provides foundation for our research. Based on the data of 285 prefecture-level cities in China from 2014 to 2019, this paper uses the fixed effect and mediation model to verify the impact and mechanism of air pollution on regional innovation. The results show that the increase in air pollution, measured by the air quality index, significantly inhibits regional innovation. Air pollution has significant funds crowding-out effect and human capital loss effect, thereby decreasing the regional innovation level, which means innovation funds and researchers play a conductive role between air pollution and regional innovation. In heterogeneity analysis, it is found that the detrimental effect of air pollution on regional innovation is significant in eastern and central China, in large- and medium-sized cities, and in cities with poor or general air quality. It indicates that developed and large-scale regions should pay more attention to air pollution control. For polluted regions, more emphasis and endeavors are needed to address air pollution problems. Besides, the inhibitory effect is more severe on incremental innovation rather than on radical innovation, which deserves the attention of enterprises engaged in incremental innovation. Therefore, we propose that targeted environmental policies and effective measures should be developed to improve air quality in the long run. Moreover, policymakers could provide strong support for innovation grants, talent subsidies, and rewards and encourage clean technological innovation through short-term trade-offs between heavily polluting and low polluting enterprises.

An overview of PROTACs: a promising drug discovery paradigm.

Proteolysis targeting chimeras (PROTACs) technology has emerged as a novel therapeutic paradigm in recent years. PROTACs are heterobifunctional molecules that degrade target proteins by hijacking the ubiquitin-proteasome system. Currently, about 20-25% of all protein targets are being studied, and most works focus on their enzymatic functions. Unlike small molecules, PROTACs inhibit the whole biological function of the target protein by binding to the target protein and inducing subsequent proteasomal degradation. PROTACs compensate for limitations that transcription factors, nuclear proteins, and other scaffolding proteins are difficult to handle with traditional small-molecule inhibitors. Currently, PROTACs have successfully degraded diverse proteins, such as BTK, BRD4, AR, ER, STAT3, IRAK4, tau, etc. And ARV-110 and ARV-471 exhibited excellent efficacy in clinical II trials. However, what targets are appropriate for PROTAC technology to achieve better benefits than small-molecule inhibitors are not fully understood. And how to rationally design an efficient PROTACs and optimize it to be orally effective poses big challenges for researchers. In this review, we summarize the features of PROTAC technology, analyze the detail of general principles for designing efficient PROTACs, and discuss the typical application of PROTACs targeting different protein categories. In addition, we also introduce the progress of relevant clinical trial results of representative PROTACs and assess the challenges and limitations that PROTACs may face. Collectively, our studies provide references for further application of PROTACs.

Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents.

7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100-1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo. These results suggested that 5b could be a promising drug candidate for treating colorectal cancer.

A Metastatic Intrahepatic Cholangiocarcinoma With HPCs Features: Report of a Case.

Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary neoplasm, which originates from the bile ducts proximal to the second-order division. ICC can be anatomically divided into two subtypes: the large duct type (mucin-production ICC, muc-ICC) and the small duct type (mixed-ICC) origins from hepatic progenitor cells (HPCs). The immunoreactivity of S100P and neural cell adhesion molecule (NCAM) are useful biomarkers to distinguish the two subtypes. In this study, we report a difficult-to-diagnose case of metastatic retroperitoneal tumor of occult hepatolithiasis-associated ICC. Besides, this case was both positive for S100P and NCAM, considered as a rare muc-ICC with the HPCs features. Tumor whole exome sequencing detection results by Genetron (China) revealed that there were 41 gene mutations in this patient. The SMAD4-p.His530ThrfsTer47 and KRAS-p.Gly12Val mutation might promote the occurrence and distant metastasis of the tumor.

Discovery of potent and selective HER2 PROTAC degrader based Tucatinib with improved efficacy against HER2 positive cancers.

HER2 is a validated therapeutic target for HER2 positive breast cancer and gastric cancer. TKIs have significantly improved the prognosis of patients with HER2 positive cancer. However, the pan-HER TKIs always caused gastrointestinal and skin side effects, and acquired drug resistance inevitable compromised their therapeutic efficacy. Herein, we describe the discovery of the first potent and selective HER2 PROTAC degrader based Tucatinib with improved antitumor activity in vitro and in vivo. The preferred selective HER2 PROTAC, CH7C4, efficiently degraded HER2 with DC50 of 69 nM and Dmax of 96%, and inhibited the proliferation of BT-474 cells with IC50 of 0.047 ± 0.006 nM via long lasting HER2 degradation and strong repression of downstream pathway. Moreover, CH7C4 had acceptable pharmacokinetic profiles with a half-life of 5.31 h, and significantly inhibited the growth of BT-474 xenografts in vivo with TGI of 73%. As the first selective HER2 PROTAC degrader with better activity in vitro and in vivo than Tucatinib, CH7C4 provides new insights into the development of new therapeutic strategy for HER2 positive cancer.

Registration of the endoluminal surfaces of the colon derived from prone and supine CT colonography.

PURPOSE: Computed tomographic (CT) colonography is a relatively new technique for detecting bowel cancer or potentially precancerous polyps. CT scanning is combined with three-dimensional (3D) image reconstruction to produce a virtual endoluminal representation similar to optical colonoscopy. Because retained fluid and stool can mimic pathology, CT data are acquired with the bowel cleansed and insufflated with gas and patient in both prone and supine positions. Radiologists then match visually endoluminal locations between the two acquisitions in order to determine whether apparent pathology is real or not. This process is hindered by the fact that the colon, essentially a long tube, can undergo considerable deformation between acquisitions. The authors present a novel approach to automatically establish spatial correspondence between prone and supine endoluminal colonic surfaces after surface parameterization, even in the case of local colon collapse. METHODS: The complexity of the registration task was reduced from a 3D to a 2D problem by mapping the surfaces extracted from prone and supine CT colonography onto a cylindrical parameterization. A nonrigid cylindrical registration was then performed to align the full colonic surfaces. The curvature information from the original 3D surfaces was used to determine correspondence. The method can also be applied to cases with regions of local colonic collapse by ignoring the collapsed regions during the registration. RESULTS: Using a development set, suitable parameters were found to constrain the cylindrical registration method. Then, the same registration parameters were applied to a different set of 13 validation cases, consisting of 8 fully distended cases and 5 cases exhibiting multiple colonic collapses. All polyps present were well aligned, with a mean (+/- std. dev.) registration error of 5.7 (+/- 3.4) mm. An additional set of 1175 reference points on haustral folds spread over the full endoluminal colon surfaces resulted in an error of 7.7 (+/- 7.4) mm. Here, 82% of folds were aligned correctly after registration with a further 15% misregistered by just onefold. CONCLUSIONS: The proposed method reduces the 3D registration task to a cylindrical registration representing the endoluminal surface of the colon. Our algorithm uses surface curvature information as a similarity measure to drive registration to compensate for the large colorectal deformations that occur between prone and supine data acquisitions. The method has the potential to both enhance polyp detection and decrease the radiologist's interpretation time.

catena-Poly[[dichloridomercury(II)]-µ-1,4-bis-[(pyridin-2-yl)meth-oxy]benzene-κN:N'].

In the title compound, [HgCl(2)(C(18)H(16)N(2)O(2))](n), the Hg(II) atom is four-coordinated in a distorted tetra-hedral environment defined by two Cl atoms and two N atoms from two 1,4-bis-(pyridin-2-ylmeth-oxy)benzene ligands. The ligand shows a non-coplanar conformation, in which the dihedral angles between the two terminal pyridine rings and the linking benzene ring are 7.275 (17) and 74.020 (14)°. The flexible ligands link the Hg(II) atoms into a chain running along [010], with an Hg⋯Hg separation of 10.335 (5) Å, which is equal to the b axis. The chains are connected by C-H⋯O and C-H⋯Cl hydrogen bonds.

catena-Poly[[dichloridozinc(II)]-µ-1,4-bis-(pyridin-2-ylmeth-oxy)benzene-κN:N'].

In the title compound, [ZnCl(2)(C(18)H(16)N(2)O(2))](n), the Zn(II) ion is tetra-hedrally coordinated by two Cl atoms and by two N atoms from different 1,4-bis-(pyridin-2-ylmeth-oxy)benzene ligands. The ligand shows a non-planar configuration, in which the dihedral angles between the two terminal pyridine rings and the linking benzene ring are 7.86 (12) and 70.74 (11)°. The flexible ligand coordinates to the Zn(II) ions, generating an infinite chain propagating along [001].

Mitochondrial-targeted deep-red fluorescent probe for ATP and its application in living cells and zebrafish.

A novel mitochondrial-targeted deep-red fluorescence ATP probe, NIR-A, is reported. The probe showed a fast, selective, and reversible response for ATP with a significant turn-on fluorescence signal at 663 nm with a large Stokes shift of 81 nm. Additionally, the introduction of TPP enabled TPP-endowed NIR-A to be enriched predominantly in the mitochondria. NIR-A was successfully applied to monitor ATP fluctuation in Ramos cells and zebrafish in real-time with good biocompatibility.