Ecological risk assessment of dissolved heavy metals in the Yangtze River Estuary and Zhejiang coastal waters, China.

The study applied a tiered ecological risk assessment method to evaluate the long-term status and trend of the ecological risks of dissolved heavy metals from 2011 to 2019 in the Yangtze River Estuary and Zhejiang coastal waters, China. The results for spring, summer, and autumn of 2019 indicated that Pb, Cd, and Zn posed no adverse ecological risk, Cu posed a potential ecological risk, and As posed an ecological risk. The annual results from 2011 to 2019 suggested that Pb, Cd, and Zn posed no adverse ecological risks, and As and Cu posed an ecological risk. The trend analysis in the nine years showed that the ecological risk of Cu is gradually decreasing, while that of As is still a concern. The overall trend is attributed to the environmental protection policies that reduced these contaminants' terrestrial sources and atmospheric sources.

Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines.

Under the catalysis of Rh2(OAc)4 (10 mol%) and binapbisphosphine ligand (±)-L3 (20 mol%) in DCE at 80 °C, the cascade cyclization of diazoimides with alkylidenepyrazolones underwent stereoselectively (dr > 20:1), affording pyrazole-fused oxa-bridged oxazocines in reasonable chemical yields. The chemical structure and relative configuration of title products were firmly identified by X-ray diffraction analysis.

Visible-Light-Driven [2 + 2] Photocycloaddition for Constructing Dimers of N,N'-Diacyl-1,4-dihydropyrazines: Experimental and Theoretical Investigation.

In this study, the visible-light-driven [2 + 2] photocycloaddition of 1,4-dihydropyrazines in solution was reported. The N,N'-diacyl-1,4-dihydropyrazines with different substituents showed completely different reactivity under the irradiation of a 430 nm blue light-emitting diode (LED) lamp. N,N'-Diacetyl-1,4-dihydropyrazine and N,N'-dipropionyl-1,4-dihydropyrazine were the only compounds capable of undergoing a [2 + 2] photocycloaddition reaction, yielding syn-dimers and cage-dimers (known as 3,6,9,12-tetraazatetraasteranes) with overall yields of 76 and 83%, correspondingly. The substituent-reactivity effect on [2 + 2] photocycloaddition of N,N'-diacyl-1,4-dihydropyrazines was investigated by density functional theory calculations. The results show that the substituents have little influence on Gibbs free energy for the [2 + 2] photocycloaddition and mainly affect the excited energy, reaction sites, and the triplet excited-state structures of 1,4-dihydropyrazines, which are closely related to whether the reaction occurs. The results offer insights into the photochemical reactivity of 1,4-dihydropyrazines and an approach for constructing dimers of N,N'-diacyl-1,4-dihydropyrazines through a solution-based visible-light-driven [2 + 2] photocycloaddition, especially for the construction of 3,6,9,12-tetraazatetraasteranes. Compared with the solid-state [2 + 2] photocycloaddition of 1,4-dihydropyrazine, this photocycloaddition will be an efficient and environmentally friendly method for synthesizing tetraazatetraasteranes with the advantages of milder reaction conditions, simple operation, adjustable reaction amounts by omitting the cocrystal growth step, etc.

Visible-Light Photocatalytic Highly Selective Oxidation of Alcohols into Carbonyl Compounds by CsPbBr3 Perovskite.

Conversion of alcohols into corresponding carbonyl compounds through an oxidation reaction with high conversion and selectivity simultaneously under mild conditions still remains a great challenge. Herein, a cost-effective and highly efficient photocatalytic protocol for selective oxidation of alcohols was developed using CsPbBr3 perovskite as a heterogeneous photocatalyst, which afforded aldehydes/ketones exclusively with a yield of 99% at ambient temperature under an air atmosphere. Moreover, the photocatalyst can be recycled at least 5 times without a significant decrease in catalytic activity. The detailed reaction mechanism was investigated by a series of quenching experiments, including Stern-Volmer experiments and electron paramagnetic resonance spectroscopy analysis as well as DFT calculations.

Pd-catalyzed decarboxylative 1,4-addition reactions of benzofuran-based azadienes with allyl phenyl carbonates.

Under the catalysis of Pd(OAc)2/dppf/Na2CO3, the decarboxylative 1,4-addition reaction of benzofuran-based azadienes with allyl phenyl carbonates took place easily and delivered the desired products in reasonable chemical yields. The chemical structure of the target compounds was clearly identified by single crystal X-ray structural analysis.

New di-spirocyclic labdane diterpenoids from the aerial parts of Leonurus japonicus.

Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.

Pregnane steroid glycosides with multidrug resistance reversal activity from the stems of Marsdenia tenacissima.

Eighteen previously unreported pregnane glycosides, namely marsdenosides S1-S18, along with 15 known analogues, have been isolated from the stems of Marsdenia tenacissima. The structures of the undescribed compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation, X-ray crystallography and acid hydrolysis. All the isolates were evaluated for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and nine ones displayed moderate MDR reversal activity with reversal folds in the range of 2.45-9.01. The most active 12-O-acetyl-20-O-benzoyl-(14,17,18-orthoacetate)-dihydrosarcostin-3-O-ß-d-thevetopyranosyl-(1 â†’ 4)-O-ß-d-oleandropyranosyl-(1 â†’ 4)-O-ß-d-cymaropyranoside increased the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil (RF = 8.93).

Chemoselective [2 + 2]/[3 + 2] Photocycloaddition of 1,4-Dihydropyridines: Experimental and Theoretical Investigation.

The photocycloaddition of 1,4-dihydropyridines (1,4-DHPs) is a main approach to synthesize structurally complex compounds, which are important intermediates for the preparation of cage compounds, such as 3,9-diazatetraasterane, 3,6-diazatetraasterane, 3,9-diazatetracyclododecane, and 6,12-diazaterakishomocubanes. The acquisition of different cage compounds depended on the chemoselectivity, which is mainly caused by the reaction conditions and structural characteristics of 1,4-DHPs. This study aimed to investigate the effect of the structural characteristics on chemoselectivity in [2 + 2]/[3 + 2] photocycloaddition of 1,4-DHPs. The photocycloadditions were conducted on the 1,4-diaryl-1,4-dihydropyridine-3-carboxylic ester with steric hindrance groups at the C3 position or chirality at the C4 position irradiated by a 430 nm blue LED lamp. When the 1,4-DHPs contained high steric hindrance groups at the C3 position, [2 + 2] photocycloaddition was the main reaction, resulting in 3,9-diazatetraasteranes with a yield of 57%. Conversely, when the 1,4-DHPs were resolved to a chiral isomer, the main reaction was [3 + 2] photocycloaddition, producing 6,12-diazaterakishomocubanes with a yield of 87%. To investigate the chemoselectivity and understand the photocycloaddition of 1,4-DHPs, density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed at the B3LYP-D3/def-SVP//M06-2X-D3/def2-TZVP level. The steric hindrance and excitation energy modulated by substituents at the C3 position and chiral carbon at the C4 position were crucial for the chemoselectivity in [2 + 2]/[3 + 2] photocycloaddition of 1,4-DHPs.

Pregnane steroids and steroid glycosides with multidrug resistance reversal activity from Marsdenia tenacissima.

Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima. Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones (1-17) being reported for the first time, including the rare cases (2 & 3) of free C21 steroids with 17α-acetyl substitution, compounds 4-7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution (7) and glycosylation at C-12 position (10 & 11). An empirical rule for the identification of C-17 configuration, in C21 steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.

Distributed fiber mountain seismic monitoring and steady-state analysis under natural earthquakes.

Mountain dynamic response monitoring plays important roles in geological disaster evolution monitoring and warning. A distributed mountain seismic monitoring and steady-state analysis method is demonstrated with distributed acoustic sensing (DAS) and a natural earthquake stimulus. In the field test, the seismic detection capability is first verified by comparing the recorded seismic waveforms from DAS and existing seismic stations. The vibration signal difference between steady-state and unsteady-state mountain parts is apparent; the operational modal analysis method is utilized to extract the response difference and to monitor the disaster evolution process. The proposed method has many advantages, including being easy to deploy, all-weather online monitoring, etc. It is believed that the proposed method will broaden the DAS application scope and promote the development of geological disaster early warning such as landslides and collapses.

Steroid glycosides from the roots of Marsdenia tenacissima.

Eleven undescribed glycosylated C21 steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.

Development of pyrazolo[3,4-d]pyrimidin-4-one scaffold as novel CDK2 inhibitors: Design, synthesis, and biological evaluation.

A series of pyrazolo[3,4-d]pyrimidin-4-one scaffold were designed and synthesized as novel CDK2 inhibitors. By analyzing the common motifs of various known inhibitors, the designed compounds 1 were virtually screen for their inhibitory activity by docking into the active pocket of CDK2. The influence of different substitutes on the docking results was investigated. A total of 15 pyrazolo[3,4-d]pyrimidin-4-ones 1 were synthesized by Paal-Knorr reaction, pyrimidine ring closure, bromination, Suzuki coupling reaction, amide formation and Knoevenagel condensation. The Cell Counting Kit-8 (CCK-8) was used to evaluate the inhibitory activity of pyrazolo[3,4-d]pyrimidin-4-ones 1 in the breast cancer cell line MCF-7 in vitro using Etoposide as a reference control substance. The screening results demonstrated that the designed compounds have significant antiproliferative activity, and compounds 1e and 1j were the most active compounds with IC50 values of 10.79 µM and 10.88 µM, respectively, being better than that of Etoposide (IC50 = 18.75 µM). The enzyme inhibition assay was carried out against CDK2, the results indicated that the compounds 1e and 1j significantly inhibited CDK2 with IC50 values of 1.71 µM and 1.60 µM.

Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study.

In the experimental process of preparing diethyl 3,5-dicarboxylate-1,4-dihydropyridine (1,4-DHP) by a Hantzsch-like reaction, it was found that a by-product named diethyl 3,5-dicarboxylate-1,2-dihydropyridine (1,2-DHP) was produced in the reaction. To discuss this phenomenon, the effects of the reaction conditions on the yield ratio of 1,4-DHP and 1,2-DHP were studied by using aromatic amines, aromatic aldehydes and ethyl propiolate as raw materials. The mechanisms for the formation of 1,4-DHP and 1,2-DHP were proposed based on the isolated intermediate named diethyl 4-((phenylamino)methylene)pent-2-enedioate generated by the Michael addition of aniline and ethyl propiolate. The transition state structures were optimized and the reaction energy barriers of intermediates in the speculated mechanisms were calculated by DFT calculations at the M062X/def2TZVP//B3LYP-D3/def-SVP level. It was found that the reaction energy barriers and dominant configurations of intermediates IM2 and IM3' are the determinants for the chemoselectivity. Together, these results demonstrate a high chemoselectivity in the synthesis of 1,4-DHPs and 1,2-DHPs by a Hantzsch-like reaction and that 1,4-DHPs and 1,2-DHPs can be easily obtained under different conditions.

Relationship between infertility-related stress and resilience with posttraumatic growth in infertile couples: gender differences and dyadic interaction.

STUDY QUESTION: Are there any gender differences and dyadic interactions in the associations between infertility-related stress and resilience and posttraumatic growth in infertile couples? SUMMARY ANSWER: Husbands' posttraumatic growth was only impacted by their own infertility-related stress and resilience, whereas wives' posttraumatic growth was influenced by their own resilience and their spouses' resilience. WHAT IS KNOWN ALREADY: Posttraumatic growth may play a significant role in protecting the infertile couples' psychological well-being and contribute to positive pregnancy outcomes. The reciprocal influence on each other within the infertile couple in terms of relationships between infertility-related stress and resilience and posttraumatic growth has been largely overlooked. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 170 couples who were recruited from the First Affiliated Hospital of Soochow University between September 2019 and January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Fertility Problem Inventory, Connor-Davidson Resilience Scale-10, and Post-traumatic Growth Inventory were used to measure infertility-related stress, resilience, and posttraumatic growth. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and resilience on the couple's own posttraumatic growth (actor effect) as well as on their partner's posttraumatic growth (partner effect). MAIN RESULTS AND THE ROLE OF CHANCE: Husbands had higher levels of resilience than wives, while no significant gender differences were found in the levels of infertility-related stress and posttraumatic growth. Posttraumatic growth correlated with each other among infertile couples. Husbands' infertility-related stress had actor effects on their own posttraumatic growth, while wives' infertility-related stress had no effect on their own or their spouses' posttraumatic growth. Husbands' resilience had actor and partner effects on their own and their wives' posttraumatic growth, while wives' resilience only had an actor effect on their own posttraumatic growth. LIMITATIONS, REASONS FOR CAUTION: First, our sample was limited to infertile Chinese couples seeking clinical treatment. Second, sociodemographic and psychological measures were self-reported. Third, as the current study is a cross-sectional study, the dynamic process of posttraumatic growth is unknown. WIDER IMPLICATIONS OF THE FINDINGS: Infertile couples should be considered as a whole in studies on infertility. Couple-based psychological interventions are critical and more effective in improving mental health among individuals with infertility. Elevating the level of resilience may contribute to improving posttraumatic growth for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives' posttraumatic growth. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Natural Science Foundation of China (Grant No. 31900783) and the College Natural Science Research Project of Jiangsu Province (Grant No.19KJD320004). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Bioactive sesquiterpenoids from the flower buds of Tussilago farfara.

Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of 13C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.

Prenylated indole alkaloids and lignans from the flower buds of Tussilago farfara.

Six new compounds including four prenylated indole alkaloids (1-4) and two lignans (5-6), along with eight known cometabolites (7-14), were isolated from the flower buds of Tussilago farfara. Structures of the new compounds were elucidated by comparison with structurally related known analogues and also by comprehensive spectroscopic analyses. Their absolute configurations were determined by a variety of means including Mosher's method, Marfey's analysis, electronic circular dichroism (ECD) exciton chirality method and ECD calculations. Our bioassays have established that compounds 1 and 2 showed potent α-glucosidase inhibitory activity with IC50 values of 105 ± 4.7 and 35.2 ± 3.2 µM, respectively, while the known 13 and 14 exerted moderate DPPH radical scavenging activity with IC50 values of 45.2 ± 2.9 and 29.2 ± 2.0 µM, respectively.

Design, Synthesis and Biological Evaluation of 4-Aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one Derivatives as a PI3Kα Inhibitor.

A novel series of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives were designed as a phosphoinositide 3-kinase α (PI3Kα) inhibitor by scaffold hopping. The target compounds, characterized by 1H-NMR, 13C-NMR and high resolution (HR)-MS, were synthesized from diethyl malonate and ethyl chloroacetate by nucleophilic substitution, ring-closure, chlorination and Suzuki reaction, etc. The biological activities were evaluated with cytotoxic activity in vitro on Uppsala 87 Malignant Glioma (U87MG) and prostate cancer-3 (PC-3) by Cell Counting Kit-8 (CCK-8). The results showed that compound 9c displayed the higher inhibition than the positive control PI-103, and high PI3Kα inhibitory activity with IC50 of 113 ± 9 nM in the same order of magnitude as BEZ235. In addition, the Log Kow values and molecular docking studies were performed to further investigate the drug-like properties of target compounds and interactions between 9c and PI3Kα.

New octadecanoid derivatives from the seeds of Ipomoea nil.

Four new octadecanoid derivatives (1-4) including a pair of enantiomers (1/2), along with 12 known analogues (5-16), were isolatedfrom the seeds of Ipomoea nil. Their structures were determined by detailed spectroscopic analyses and comparison with reported data of structurally related compounds, with the absolute configurations of 1 and 2 being assigned by an in situ dimolybdenum ECD method. Our bioassays revealed that these isolates did not show ABTS radical scavenging activity while 10 and 13 displayed better α-glucosidase inhibitory activity than the positive control acarbose (IC50 167.7 ± 1.55 µmol·L-1), with IC50 of 92.73 ± 3.12 and 11.39 ± 2.18µmol·L-1, respectively.

Chromane Enantiomers from the Flower Buds of Tussilago farfara L. and Assignments of Their Absolute Configurations.

Fourteen chromane derivatives of seven pairs of enantiomers (1-14) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α-glucosidase inhibitory activities.