Divergent Synthesis of α-(1,3,5-Triazinylthio)-ketones and Thiazolo[3,2-a][1,3,5]triazines from 1,3-Dicarbonyl compounds or Chalcones with 1,3,5-Triazine-2-thiols.

An efficient synthesis of α-(1,3,5-triazinylthio)-ketones from 1,3-dicarbonyl compounds with 1,3,5-triazine-2-thiols has been developed. The reaction proceeds through the C-C bond cleavage and C-S bond reconstruction of 1,3-dicarbonyl compounds, and ß-keto esters, ß-keto amides, and 1,3-diones were tolerated. In addition, the annulation of 1,3,5-triazine-2-thiols with chalcones has been achieved for the synthesis of thiazolo[3,2-a][1,3,5]triazines. The method occurred in moderate to good yields and tolerated chalcone with a broad functional group.

Role of 7-methylxanthine in myopia prevention and control: a mini-review.

Myopia is becoming increasingly common. By 2050 around 10% of the world's population is expected to be highly myopic (<-5 diopters) and therefore particularly at risk of suffering from sight-threatening complications. Currently used myopia control treatments, such as multifocal soft contact lenses or spectacle lenses, orthokeratology, and atropine eyedrops, either do not completely arrest myopia progression or are associated with significant ocular and possibly systemic side effects. A new candidate for pharmaceutical control of myopia progression and excessive eye elongation, the non-selective adenosine antagonist 7-methylxanthine (7-MX), appears to be non-toxic and effective in reducing myopia progression and axial eye growth in experimental and clinical studies. The latest findings regarding 7-MX for myopia control and evaluate its potential as a supplement to existing treatment options were reviewed.

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Direct arterial puncture for hemodialysis, a neglected but simple and valuable vascular access.

INTRODUCTION: The purpose of this study is to present the prevalence and effects of direct arterial puncture (DAP) for hemodialysis patients, and to introduce optimal option for the vascular access (VA) in certain hemodialysis patients with poor condition of vascular or cardiac function in a compelling situation. METHODS: This was a cross-sectional study. Demographic characteristics and laboratory data were extracted from the health care system. Relevant DAP information was collected by a questionnaire. Case-control matching was performed to compare the hemodialysis adequacy between DAP and other VAs. RESULTS: A total of 526 patients were selected for analysis by convenience sampling, of which 38 patients relied https://www.baidu.com/link?url=eaDh8Hn-yZGJyDB0_h4zBenKd7qY1yX-KNxO-qU49gktQOGTJJg3slTjIbG095st4hRfprQIHRjfhfeGOZyH73y8tvSUCwMmvWbUhyix2ZK on DAP for hemodialysis. The main reasons using DAP for hemodialysis included the cost of arteriovenous access creation or maintenance in 19(50%) patients and the poor condition of vascular or cardiac function in 14 (39.5%) patients. Some complications of DAP occurred, such as aneurysm or pseudoaneurysm in 16(42.1%) patients, infiltration in 12 (31.6%) patients. Differences in hemodialysis adequacy were not statistically significant between DAP and other types of VA. CONCLUSION: In conclusion, DAP can meet the need of prescription hemodialysis, yet it has several limitations. Although the patients in our study were long-term dependent on DAP for hemodialysis with various reasons, we do not recommend DAP as a long-term vascular access if better options are available. However, DAP should not be overlooked to be a supplemental VA for hemodialysis with adequate blood flow and availability for individuals with poor condition of vascular or cardiac function in a compelling situation.

Diversity-oriented synthesis of imidazo[1,2-a][1,3,5]triazine derivatives from 2-amine-[1,3,5]triazines with ketones.

An I2-mediated annulation of 2-amino[1,3,5]triazines and ketones for the synthesis of imidazo[1,2-a][1,3,5]triazines is presented. Electron rich, or electron poor acetophenone and heterocycle ketones, as well as propiophenone, are functionalized with 2-amino-[1,3,5]triazines. Another class of imidazo[1,2-a][1,3,5]triazines tethered with an additional 1,2-dicarbonyl motif through the combination of annulation and C-H functionalization were obtained instead by changing the reaction conditions. The new methods are practically straightforward and applicable on a gram scale.

All-trans retinoic acid increases ARPE-19 cell apoptosis via activation of reactive oxygen species and endoplasmic reticulum stress pathways.

AIM: To explore the apoptosis of ARPE-19 cells after the treatment with different doses of all-trans-retinoic acid (ATRA). METHODS: ARPE-19 cells were used in the in-vitro experiment. Flow cytometry assay was employed to evaluate the level of reactive oxygen species (ROS) and apoptosis. The effects of ATRA (concentrations from 2.5 to 20 µmol/L) on the expression of endoplasmic reticulum stress (ERS) markers in vitro were evaluated by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR) assays. The contribution of ROS and ERS-induced apoptosis in vitro was determined by using N-acetyl-L-cysteine (NAC) and Salubrinal, an antagonist of NAC and ERS, respectively. RESULTS: Flow cytometry showed that ATRA significantly increased ARPE-19 cell apoptosis and ROS levels in each group (F=86.39, P<0.001; F=116.839, P<0.001). Western blot and qRT-PCR revealed that levels of CHOP and BIP were elevated in a concentration-dependent pattern after the cells were incubated with ATRA (2.5-20 µmol/L). The upregulation of VEGF-A and CHOP induced by ATRA could be inhibited by NAC (antioxidant) and Salubrinal (ERS inhibitor) in vitro. CONCLUSION: ATRA induces the apoptosis of ARPE-19 cells via activated ROS and ERS signaling pathways.

Rescue of cognitive deficits in APP/PS1 mice by accelerating the aggregation of ß-amyloid peptide.

BACKGROUND: Brain amyloid deposition is one of the main pathological characteristics of Alzheimer's disease (AD). Soluble oligomers formed during the process that causes ß-amyloid (Aß) to aggregate into plaques are considered to have major neurotoxicity. Currently, drug development for the treatment of Alzheimer's disease has encountered serious difficulties. Our newly proposed solution is to accelerate the aggregation of Aß to reduce the amount of cytotoxic Aß oligomers in brain tissue. This strategy differs from the existing strategy of reducing the total Aß content and the number of amyloid plaques. METHOD: In this study, we screened a small library and found that a flavonoid compound (ZGM1) promoted the aggregation of ß-amyloid (Aß). We further verified the binding of ZGM1 to Aß42 using a microscale thermophoresis (MST) assay. Subsequently, we used dot blotting (DB), transmission electron microscopy (TEM), and thioflavin T fluorescence (ThT) measurements to study the aggregation of Aß under the influence of ZGM1. By using cell experiments, we determined whether ZGM1 can inhibit the cytotoxicity of Aß. Finally, we studied the protective effects of ZGM1 on cognitive function in APPswe/PS1 mice via behavioral experiments and measured the number of plaques in the mouse brain by thioflavin staining. RESULTS: ZGM1 can bind with Aß directly and mediate a new Aß assembly process to form reticular aggregates and reduce the amount of Aß oligomers. Animal experiments showed that ZGM1 can significantly improve cognitive dysfunction and that Aß plaque deposition in the brain tissue of mice in the drug-administered group was significantly increased. CONCLUSION: Our research suggests that promoting Aß aggregation is a promising treatment method for AD and deserves further investigation.

Copper-Catalyzed Tandem Reactions of 2-Amine-[1,3,5]triazines with Nitriles.

Copper-catalyzed intermolecular annulation of 2-amine-[1,3,5]triazines and aryl nitriles for the synthesis of [1,2,4]triazolo[1,5- a][1,3,5]triazines via N-C bond formation and oxidative N-N coupling [oxidative 3 + 2 cyclization] is presented. A wide range of aryl nitriles, including electron-rich benzonitriles, electron-poor benzonitriles, 2-cyanothiophene, and 4-cyanopyridine, were all functionalized with 2-amine-[1,3,5]triazines. Furthermore, amidation of 2-amine-[1,3,5]triazines via Cu-catalyzed C-CN bond cleavage of phenylacetonitriles is also demonstrated. The reaction occurred in moderate to satisfactory yields and tolerated alkyl- or aryl-substituted 2-amine-[1,3,5]triazines. Aniline, aminopyridine, and aminopyrimidine also afforded the desired products.

Ruthenium-catalyzed synthesis of arylethyl 1,3,5-triazines from arylallyl alcohols and biguanides.

An efficient ruthenium-catalyzed synthesis of alkyl-1,3,5-triazies from arylallyl alcohols and biguanides has been developed. The reaction occurred in moderate to good yields and tolerated heterocyclic or aryl allyl alcohols containing functionalities such as alkanes, ethers, and halogens. The reaction proceeds through a one-pot sequence of transfer hydrogenation and condensation steps.

Formal total synthesis of salvianolic acid N.

An efficient synthetic pathway for the total synthesis of salvianolic acid N has been reported. The key reaction steps, the Wittig reaction for Z-stereoselectivity and an intramolecular cyclization for a seven membered ring skeleton, have been optimized to improve the synthetic feasibility and provide the best conditions in terms of yield. Moreover, a notable reaction is the reaction of the deprotected allylic group with Pd catalyst. An improved overall yield of 11% has been achieved for salvianolic acid N starting from 3,4-dimethoxybenzaldehyde in 11 steps.

Effect of dopamine on bone morphogenesis protein-2 expression in human retinal pigment epithelium.

AIM: To investigate the effect of dopamine on bone morphogenesis protein-2 (BMP-2) expression in retinal pigment epithelium (RPE) cells in vitro. METHODS: ARPE-19 cells as a human RPE cell line were cultured with dopamine for different times (2, 4, 6, 8, 12, 16 and 24h) or with different concentrations (0.1, 1, 2, 5, 10, 20, and 100 µg/mL) in vitro. BMP-2 mRNA expression level in ARPE-19 cells was analyzed with real-time polymerase chain reaction (PCR) analysis and BMP-2 protein level was measured with Western blot analysis. The active form of BMP-2 in the culture medium was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression level of BMP-2 increased significantly cultured with 20 µg/mL dopamine, at different time points (P<0.05). BMP-2 mRNA level peaked 2h and the protein level peaked at 6 and 8h after treatment. The concentrations of secreted BMP-2 elevated at 12h and peaked at 24h (P<0.05) in a time-dependent manner. Treated with 100 µg/mL dopamine for 6h, the expression levels of BMP-2 mRNA and protein in ARPE-19 cells were enhanced significantly compared to that in the untreated cells (P<0.05). And secreted BMP-2 protein in the cell culture supernatant was also increased (P<0.05). CONCLUSION: Dopamine up-regulate BMP-2 expression in RPE cells, and this may be associated with its inhibitive effect on myopia development.

2,4-Diamino-1,3,5-triazine-enabled Cu-catalyzed direct sulfonamidation of aromatic C-H bonds.

An efficient copper acetate catalyzed sulfonamidation of arenes via C-H bond activation directed by a 2,4-diamino-1,3,5-triazine chelating group under oxygen as a terminal oxidant has been developed. The reaction shows good regioselectivity and functional group tolerance, as well as providing a straightforward methodology for the preparation of ortho-monosulfonamidated arene derivatives in moderate to high yields. The sulfonamidation at the gram scale can be performed with a good yield.

Copper-Catalyzed Synthesis of Substituted 2,4-Diamino-1,3,5-triazines from 1,1-Dibromoalkenes and Biguanides.

An efficient copper-catalyzed synthesis of substituted 2,4-diamino-1,3,5-triazines from 1,1-dibromoalkenes and biguanides under mild conditions has been developed. The reaction occurred in moderate to good yields and tolerated alkyl-, heterocyclic-, or aryl-substituted 1,1-dibromoalkenes containing functionalities such as nitriles, ethers, and halogens. Monosubstituted to tetrasubstituted biguanidines also afforded the desired products.

Copper(ii) catalyzed iodine-promoted oxidative cyclization of 2-amino-1,3,5-triazines and chalcones: synthesis of aroylimidazo[1,2-a][1,3,5]triazines.

An efficient copper(ii) catalyzed iodine-promoted synthesis of aroylimidazo[1,2-a][1,3,5]triazines from 2-amino-1,3,5-triazines and chalcones under mild conditions has been developed. The reaction occurred with good yields and excellent regioselectivities, and tolerated chalcone containing functionalities such as ethers, halogens, and nitro groups. The successful application of this methodology for a gram-scale reaction indicates its potential for bulk synthesis.

Copper-catalyzed arylation of biguanide derivatives via C-N cross-coupling reactions.

An efficient copper-catalyzed cross-coupling reaction of biguanide hydrochloride derivatives with both aryl iodides and bromides under mild conditions has been developed. The reaction occurred in good yields and tolerated aryl halides containing functionalities such as nitriles, sulfonamides, ethers, and halogens. Alkyl and cyclic substituted biguanidines were also well tolerated.

Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides.

A co-catalyst of (PPh3)AuCl/AgOTf for the intermolecular hydroamination of allenes with sulfonamides is shown. The reaction proceeded smoothly under mild conditions for differently substituted allenes giving N-allylic sulfonamides in good yields with high regioselectivity and E-selectivity.

Effects of 7-methylxanthine on form-deprivation myopia in pigmented rabbits.

AIM: To determine the effect of 7-methylxanthine (7-MX) on the posterior sclera of form-deprivation myopia (FDM) in pigmented rabbits. METHODS: Sixteen pigmented rabbits were monocularly deprived (MD) by suturing the right eyelids after natural eye opening (ten-day old) for a period of 30 days. Two groups of pigmented rabbits were fed either 7-MX (30 mg per kg body weight; n=8) or vehicle control (saline equal volume with 7-MX; n=8). Ocular refractions, axial lengths and body weights were measured at the start and the end of the experiment 30 days later. Electron microscopy was used to measure and determine the collagen fibril diameters in the posterior pole of sclera. RESULTS: In vehicle control MD pigmented rabbits, 30 days of MD produced -1.10D±0.78D of myopia and the axial length increased 0.51mm±0.09mm. In MD pigmented rabbits fed with 7-MX, 30 days of MD induced only -0.21D±0.11D of myopia and the axial length increased 0.07mm±0.10mm. There was significant change in axial length of vehicle control MD pigmented rabbits (13.11mm±0.19mm versus 12.60mm±0.06mm; P=0.03). The changes in refraction and axial length of two MD groups' contralateral eyes during the 30 days were not significantly different (2.75D±0.27D versus 2.75D±0.35D, P>0.05; 12.60mm±0.06mm versus 12.45mm±0.14mm, P>0.05). The weights of the two groups pigmented rabbits had no significant changes (187g±22.1g versus 189g±19.3g, P>0.05). The diameter of scleral collagen fibers increased in both eyes of 7-MX treated pigmented rabbits. There was significant difference in collagen fibril diameters of inner layer (111.34nm±28.30nm versus 94.80nm±27.52nm, P=0.002) and outer layer (167.92nm±55.82 nm versus 144.04 nm±47.02nm, P=0.016) in the posterior sclera between the myopic eyes of vehicle control MD group and contralateral eyes of 7-MX treated MD group. CONCLUSION: 7-MX appears to prevent FDM in pigmented rabbits by remodeling the posterior sclera.

Characteristics of the macula in amblyopic eyes by optical coherence tomography.

AIM: To test the hypothesis that amblyopic neuroretina may have an altered thickness when compared to the normal. METHODS: Twenty-five amblyopic, young patients between the ages of 7 and 11 years old were studied. The interested neuroretina areas are defined into 10 sub-regions according to superior-inferior, nasal-temoral, and peri-para axis, which cross the fovela structure. The thicknesses of ten, defined macular regions were separately measured by optical coherence tomography (OCT) and analyzed by t-test. RESULTS: The average thickness of neuroretina in the exact foveola of the amblyopic eyes is larger than that of normal eyes (P<0.05), but the other nine regions have no significant difference. Interestingly, in both the normal and amblyopic eyes, the temporal area looks thinner than other quadrants (P<0.05). CONCLUSION: Thickness alteration may be associated with amblyopic disorders in young patients. Studying a larger volume of subjects of similar age is required to confirm this observation.

Distribution of bone morphogenetic protein receptors in human scleral fibroblasts cultured in vitro and human sclera.

AIM: To investigate the distribution of bone morphogenetic protein receptors (BMPRs) in human scleral fibroblsasts (HSFs) and in human sclera. METHODS: Primary HSFs were cultured in vitro. The mRNA levels of BMP-2 and BMPRs in HSFs were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein distributions of BMP-2 and BMPRs in HSFs were further detected by immunocytofluorescence and western blot. Their protein expression was also detected in frozen human posterior scleral sections by immunohistofluorescence. RESULTS: BMP-2 and BMPRs were expressed in both HSFs and human sclera not only at mRNA level but also at protein level. The expressions of BMPRIA and BMPRII were higher than that of BMPRIB in the cytoplasm and cell membrane of HSFs in vitro. Western blot further verified the results of immunocytofluorescence. In human sclera, BMP2, BMPR IB and BMPR II were found to be expressed in the cytomatrix of HSF, and weak signal was detected about BMPRIA. CONCLUSION: BMP-2 and all three subtypes of BMPRs were found in HSFs and may play a role in scleral remodeling.

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles.

A gold-catalyzed oxidation of arylallenes to form α-diketones and aldehydes in good yields is presented. Further directed synthesis of quinoxalines and benzimidazoles, via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine, was achieved in high yields.