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We evaluated the relative attribution and interactions of treatment and patient-related risk factors for second primary malignancies (SPMs) in cervical and endometrial cancer survivors.Stage I-III cervical and endometrial cancer survivors' data from the Surveillance, Epidemiology, and End Results (SEER) registry between January 1988 and December 2015 were analyzed. The standardized incidence ratio (SIR), excess absolute risk (EAR), and corresponding 95% confidence interval (95% CI) values were calculated. Analyses were classified based on proxies of human papillomavirus (HPV), smoking, hormone, and radiotherapy (RT) status. Additive and multiplicative interactions were assessed.Cervical cancer survivors had a higher risk for developing potentially HPV and smoking-related SPMs, especially in the RT group (SIRRT, HPV, and smoking promote SPMs in cervical cancer to different extents. The SPM burden in cervical cancer survivors could be mostly attributed to smoking and RT and their interactions.

The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination.Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence-based mortality (IBM), and 1-year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute's Joinpoint Regression Program. Age-period-cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990-2019) as a likely validation set. Joinpoint and age-period-cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992-2011 and sharply decreased thereafter by -2.3% annually (95% CI: -3.5% to -1.1%). IBM peaked in 2013 (age-standardized mortality rate: 6.98 per 100,000 person-years) in the US population. IBM started to decrease significantly in 2013 by -3.2%/year (95% CI: -5.4% to -1.1% per year) after a continuous increase of 3.5% annually during 1993-2013. Overall, the 1-year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60-69 and born between 1952-1957 were found.We found significantly decreased overall HCC-specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.

We reported an electrochemical intramolecular C–H amination approach to construct benzimidazole-fused phenanthridines. This electrochemical approach was compatible with a variety of functional groups, including ester, silyl, thioether, pyridyl and amine groups. With the triarylamine-mediated and direct oxidation strategies, the intramolecular C–H amination proceeds with high regioselectivities under oxidant- and metal-free conditions. Moreover, this protocol provided an alternative approach to access organic luminophores.

A series of Schiff’s base derivatives was rationally designed, synthesized, and evaluated as multi-function agents for the treatment of Alzheimer’s disease (AD). The results revealed that compound 3b was a novel multifunctional agent. It acted as a highly selective monoamine oxidase-B inhibitor (IC50 = 8.4 nM), which was explained by the docking study. Compound 3b also was an antioxidant agent (2.3 eq) and could significantly inhibit self-induced Aβ1-42 aggregation (31.8%). Meanwhile, compound 3b was a selective metal chelator and could inhibit Cu2+-induced Aβ1-42 aggregation (62.3%). Furthermore, compound 3b presented good neuroprotective effects on H2O2-induced PC12 cell injury. More importantly, compound demonstrated good blood brain barrier permeability and druglike properties. Therefore, compound 3b, a promising multi-targeted active molecule, offers an attractive starting point for further study in the drug-discovery process against AD.

In this study, a series of naringenin

We developed an oxidant- and transition-metal-free approach to construct six-membered cyclic phosphinamides via an intramolecular electrochemical C-H phosphinamidation process. With

In this work, a series of naringenin-O-carbamate derivatives was designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD) through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c showed good antioxidant potency (ORAC = 1.0 eq), and it was a reversible huAChE (IC

BACKGROUND: Since the end of 2019, the coronavirus disease (COVID-19) outbreak rapidly became a pandemic. The psychological state of people during the COVID-19 pandemic has gained interest. Our aim was to study the prevalence of anxiety, depression, and stress in college students during the COVID-19 pandemic. Methods: A systematic search of Medline, Embase, Web of Science, and the Cochrane Library was conducted up to September 20, 2020. Reviewers independently assessed full-text articles according to predefined criteria. Stata14/SE was used to calculate the prevalence and 95% confidence intervals (CIs) of anxiety, depression, and stress among college students from different countries. A random effects model was adopted. The Egger test was used to determine publication bias. Results: A total of 280 references were retrieved, and 28 papers met our inclusion criteria, for a total of 436,799 college students. Thirteen studies involved non-Chinese college students, and 15 studies involved Chinese college students. The prevalence of anxiety, depression, and stress was 29% (95% CI, 19-25%), 37% (95% CI, 32-42%), and 23% (95% CI, 8-39%), respectively. Conclusion: The COVID-19 pandemic has had a negative psychological effect on college students, and the prevalence of anxiety, depression, and stress among Chinese college students is lower than among non-Chinese college students.

Most hepatocellular carcinoma (HCC) patients have dismal prognoses because they are already in the advanced stage at the time of initial diagnosis and are unable to undergo upfront surgery. Recent studies of immune checkpoint inhibitors (ICIs) and antiangiogenic agents (AAAs) have shown encouraging results for unresectable HCC (uHCC). Here, we report a patient with uHCC who was treated with a combination of anlotinib and sintilimab (sintilimab 200 mg, intravenous glucose tolerance test, q21d and anlotinib 12 mg, orally, d1-14, q21d), an analog of the combination of lenvatinib and pembrolizumab with much lower cost. The patient with recurrent uHCC was downstaged to resectable disease by the combination therapy. After eight cycles of treatment with anlotinib and sintilimab, the patient underwent a second operation. The histology of the resected mass revealed a major and almost complete pathological response. However, this patient was diagnosed with type I diabetes mellitus with ketoacidosis after nearly 10 cycles of combination treatment with anlotinib and sintilimab. Active follow-ups revealed no signs of local recurrence or distant failure. In conclusion, this case report demonstrated that the combination of anlotinib and sintilimab, one of the strategies combining ICIs with AAAs, showed promising efficacy in the treatment of uHCC patients.

To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of chalcone-O-carbamate derivatives was designed and synthesized based on the multitarget-directed ligands strategy. The in vitro biological activities were evaluated including AChE/BChE inhibition, MAO-A/MAO-B inhibition, antioxidant activities, Aβ1-42 aggregation inhibition, metal-chelating properties and neuroprotective effects against H2O2-induced PC12 cell injury. The results showed compounds 5b and 5h indicated highly selective BChE inhibitory activity with IC50 values of 3.1 μM and 1.2 μM, respectively and showed highly selective MAO-B inhibitory potency with IC50 values of 1.3 μM and 3.7 μM, respectively. In addition, compounds 5b and 5h could inhibit self-induced Aβ1-42 aggregation with 63.9% and 53.1% inhibition percent rate, respectively. Particularly, compound 5b was a potent antioxidant agent and neuroprotectant, as well as a selective metal chelator by chelating Cu2+ and Al3+. Moreover, compound 5b could inhibit and disaggregate Cu2+-induced Aβ1-42 aggregation, which was further supported by the TEM images. Furthermore, compounds 5b and 5h could cross the blood-brain barrier (BBB) in vitro and conformed to the Lipinski's rule of five. Finally, the in vivo assay exhibited that compound 5b could improve scopolamine-induced cognitive impairment. Taken together, these results revealed that compound 5b might be a potential multifunctional agent for the treatment of AD, and deserved to do further structure optimization.

To discover multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of indanone–chalcone hybrid compounds were designed and synthesized based on the multitarget-directed ligand strategy. Their monoamino oxidases (MAO-A and MAO-B) and Aβ1–42 aggregation inhibitory activities were evaluated. The results were shown that all synthetic compounds exhibited mostly good multifunctional activities. Among all, compound TM-11 represented the best Aβ1–42 aggregation inhibitory potency (IC50 ~1.8 μM) and good disaggregation activity (IC50 ~7.9 μM). Both TEM images and docking studies provided good reasonable explanation to the hypothesis. Meanwhile, compound TM-11 was a selective MAO-B inhibitor, as well as a neuroprotective agent against Aβ1–42-induced toxicity. Based on the structural considerations, the lipophilicity of the compound TM-11 could render to pass through blood−brain barrier (BBB) in vitro in accordance with the Lipinski’s rule of five. In conclusion, these results were suggested that compound TM-11 might be a potential multifunctional agent for the treatment of AD.

Background: Cutaneous squamous cell carcinoma (CSCC) is the most deadly disease among nonmelanoma skin cancers. LINC00641 plays a role in various cancers, but its role in CSCC has not been reported...

Herein, combining 1,2,3,4-tetrahydroisoquinoline and benzylpiperidine groups into cinnamic acid derivatives, a series of novel cinnamic acid hybrids was rationally designed, synthesized and evaluated by the multi-target-directed ligands (MTDLs) strategy. Hybrid 4e was the most promising one among these hybrids with a reversible huBuChE inhibitor (IC50 = 2.5 μM) and good MAO-B inhibition activity (IC50 = 1.3 μM) and antioxidant potency (ORAC = 0.4 eq). Moreover, compound 4e significantly inhibited self-mediated Aβ1-42 aggregation (65.2% inhibition rate). Compound 4e exhibited remarkable anti-inflammatory propery and neuroprotective effect. Furthermore, compound 4e displayed favourable blood–brain barrier penetration via parallel artificial membrane permeation assay (PAMPA). The obtained results also revealed that compound 4e significantly improved dyskinesia recovery rate and response efficiency on AD model zebrafish. Further, 4e did not show obvious acute toxicity at dose up to 1500 mg/kg in vivo and improved scopolamine-induced memory impairment. Importantly, compound 4e showed good stability in both artificial gastric fluid and artificial intestinal fluid. Therefore, compound 4e presented a promising multi-targeted active molecule for treating AD.

A novel series of ferulic acid derivatives was designed and synthesized on the basis of the multi-target-directed ligands strategy for the treatment of Alzheimer's disease (AD). In vitro results revealed that all the target compounds were highly effective and selective butyrylcholinesterase (BuChE) inhibitors. In particular, compound TM-10 showed the best BuChE inhibitory activity, with IC50 = 8.9 nM, and remarkable monoamine oxidase A and B inhibitory potency, with IC50 = 6.3 and 8.6 μM, respectively. TM-10 could inhibit (53.9%) and disaggregate (43.8%) self-induced amyloid-β peptide (Aβ) aggregation. In addition, TM-10 exhibited potent antioxidant activity (ORAC = 0.52 equiv) and neuroprotective effect against Aβ1-42-mediated SH-SY5Y neurotoxicity, and it acted as an autophagic activator. TM-10 also showed good blood-brain barrier penetration. Furthermore, TM-10 exhibited a favorable dyskinesia recovery rate and response efficiency on an AlCl3-induced zebrafish AD model and a potent neuroprotective effect on Aβ1-40-induced zebrafish vascular injury. Further, in vivo assays demonstrated that TM-10 showed low acute toxicity, and the step-down passive avoidance test indicated that this compound could improve scopolamine-induced memory deficit in mice. Therefore, the present study displays evidence that TM-10 is a potent, multi-functional agent against AD and could be a promising lead candidate for anti-Alzheimer's disease drug development.

Maternal thyroid hormones (THs) play an essential role in the embryonic and larval development of fish. Previous studies in fish have reported that parental exposure to thyroid disrupting chemicals (TDCs) changed maternal TH levels in the offspring; however, whether this transgenerational thyroid endocrine disruption can further disturb the early development of the offspring still remains largely unknown. Bisphenol S (BPS), a substitute of bisphenol A, has been reported to be a potential TDC. In this study, zebrafish (F0) were exposed to environmentally relevant concentrations (1, 10, and 100 μg/L) of BPS from 2 h post-fertilization to 120 days post-fertilization and then paired to spawn. Plasma levels of thyroxine (T4) were significantly decreased in F0 females while 3,5,3′-triiodothyronine (T3) plasma levels were significantly increased in F0 females and males; moreover, TH content in eggs (F1) spawned by exposed F0 generation exhibited similar changes as the F0 females, with significant decreases in T4 and increases in T3, demonstrating BPS-induced maternal transfer of thyroid endocrine disruption. Further, excessive levels of maternal T3 in the offspring resulted in delayed embryonic development and hatching, swim bladder inflation defect, reduction in motility, developmental neurotoxicity, and lateral stripe hypopigmentation in non-exposed F1 embryos and larvae. These results highlight the adverse effects on the early development of offspring induced by transgenerational thyroid endocrine disruption, which have been ignored by previous studies. Therefore, these results can further improve our understanding of the ecological risks of TDCs.

A practical, electrochemical method is developed for the direct dehydrogenative lactonization of C(sp2/sp3)–H bonds under external oxidant- and metal-free conditions, delivering diverse lactones, including coumarin derivatives with excellent regioselectivity. The scalable nature of this newly developed electrochemical process was demonstrated on a 40 g scale following an operationally simple protocol. The remote lactonization of C(sp3)–H bonds would constitute an important synthetic advance toward electrochemical C–O bond formation.

A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer’s disease (AD). The results showed that compound TM - 9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B ( hu AChE, hu BuChE, and hu MAO-B with IC 50 values of 1.2 μM, 3.8 μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM - 9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM - 9 abided by Lipinski’s rule of five. Furthermore, our investigation proved that TM - 9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro . The results suggest that compound TM - 9 , an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer’s disease.

Ulcerative colitis (UC) is a serious digestive system disease. Furthermore, the activation of C3a/C3aR axis promoted the expression of caspase-11. And higher levels of caspase-11 could induce the pyroptosis and inflammation of cells. However, some studies suggested that caspase-11 could promote and suppress the inflammation during the development of UC. In addition, whether C3a/C3aR axis could affect the development of UC by modulating the expression of caspase-11 is unclear. We established the UC rat model in this study. Next, the C3aR inhibitor was used to treat these rats at diverse stages of UC. Next, the HE staining was performed to detect the intestinal damage. ELISA was performed to reveal the expression of IL-6 and TNF-α in different stages of UC. Western blotting was used to detect the expression of caspase-11 and C3aR in different stages of UC. Stimulation of C3aR inhibitor in early stage of UC promoted the expression of C3aR and caspase-11 in later stage of UC. Treatment of C3aR inhibitor in later stage of UC inhibited the expression of C3aR and caspase-11 in later stage of UC. Furthermore, application of C3aR inhibitor in early stage of UC aggravates the damage of colon tissue and enhanced the secretion of TNF-α and IL-6 in the later stage of UC. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and suppressed the production of TNF-α and IL-6 in the later stage of UC. Application of C3aR inhibitor in early stage of UC induced the poor prognosis of UC by upregulating the expression of caspase-11. Treatment of C3aR inhibitor in later stage of UC relieved the symptoms of UC and lead to the favorable prognosis of UC by inhibiting the expression of caspase-11.

In this work, we have developed a novel series of multi-target-directed ligands to address low levels of acetylcholine (ACh), oxidative stress, metal ion dysregulation, and the misfolded proteins. Novel apigenin-donepezil derivatives, naringenin-donepezil derivatives, genistein-donepezil derivatives and chalcone-donepezil derivatives have been synthesized, in vitro results showed that TM-4 was a reversible and potent huAChE (IC50 = 0.36 μM) and huBChE (IC50 = 15.3 μM) inhibitor, and showed potent antioxidant activity (ORAC = 1.2 eq). TM-4 could significantly inhibit self-induced Aβ1-42 aggregation (IC50 = 3.7 μM). TM-4 was also an ideal neuroprotectant, potential metal chelation agent, and it could inhibit and disaggregate huAChE-induced and Cu2+-induced Aβ aggregation. Moreover, TM-4 could activate UPS degradation pathway in HT22 cells and induce autophagy on U87 cells to clear abnormal proteins associated with AD. More importantly, TM-4 could cross BBB in vitro assay. In addition, in vivo assay revealed that TM-4 exhibited remarkable dyskinesia recovery rate and response efficiency on AlCl3-induced zebrafish AD model, and TM-4 indicated surprising protective effect on Aβ1-40-induced vascular injury. TM-4 presented precognitive effect on scopolamine-induced memory impairment. And the regulation of multi-targets for TM-4 were further conformed through transcriptome sequencing. More interesting, the blood, urine and feces metabolism in rat and rat/human liver microsome metabolism towards TM-4 were also investigated. Overall, TM-4 is a promising multi-function candidate for the development of drugs to Alzheimer’s disease.

Phytochemical study of the EtOAc fraction (active extract) of the fruits of Ulmus pumila L. resulted in the isolation of thirteen flavane derivatives, and they were identified by their precise spectral data and literature. All the compounds (1-13) were obtained from the fruits of U. pumila L. for the first time. Meanwhile, the compounds (1-13) were assayed for their hepatoprotective and neuroprotective activities, respectively. Compounds 1, 2, 5, 7 and 8 (10μM) exhibited remarkable hepatoprotective activities, and compounds 9, 10, and 13 showed significant neuroprotective activities with IC50 values of 4.08, 5.34, and 2.02μM, respectively.

Here we reported novel apigenin-rivastigmine hybrids were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, their activity in vitro results revealed that compound 3d showed significant antioxidant potency (ORAC = 1.3 eq), and it was a reversible huAChE (IC50 = 6.8 μM) and huBChE (IC50 = 16.1 μM) inhibitor. 3d also served as a selective metal chelator, and it significantly inhibited and disaggregated self-mediated and Cu2+-mediated Aβ1-42 aggregation, and also inhibited hAChE-mediated induced Aβ1-40 aggregation. Compound 3d exhibited remarkable neuroprotective effect and hepatoprotective activity. In addition, compound 3d presented favourable blood-brain barrier penetration in vitro and drug-like property. Further, the in vivo assay displayed that 3d indicated remarkable dyskinesia recovery rate and response efficiency on AD zebrafish, and exhibited surprising protective effect on Aβ1-40-mediated zebrafish vascular injury. More importantly, 3d did not indicate obvious acute toxicity at dose up to 2000 mg/kg, and could improve scopolamine-induced memory impairment. Subsequently, the regulation of multi-targets for 3d were further confirmed through transcriptome sequencing of brain hippocampi, which also offered novel potential targets and opened a new way to treat Alzheimer’s disease. More interestingly, the metabolism of 3d in vitro indicated that 4 metabolites in rat liver microsome metabolism, 2 metabolites in human liver microsome metabolism, and 4 metabolites in intestinal flora metabolism, which offered supports for the preclinical study of 3d. Overall, this study exhibited that compound 3d was a promising advanced compound targeted multiple factors associated with AD.

Childhood hypertension has become an important public health issue. This study explored a novel indicator, namely, childhood lipid accumulation product (CLAP), which is associated with hypertension among children and adolescents. A total of 683 children and adolescents aged 8-15 years were measured for body weight, height, waist circumference (WC), abdominal skinfold thickness (AST), triacylglycerol (TG), blood pressure, dietary behaviors, and physical activity time. The novel childhood lipid accumulation product (CLAP) was the product of WC, AST, and TG (CLAP = WC (cm) × AST (mm) × TG (mmol/L)). The logarithmic CLAP (LnCLAP), height, weight, WC, WHtR, BMI, AST, and TG were standardized for sex and age using the z-score method (standardized variables: SLnCLAP, Sheight, Sweight, SWC, SWHtR, SBMI, SAST, and STG). The results showed that the overall prevalence of hypertension was 11.6% (13.1% in boys and 9.7% in girls). SLnCLAP ≥ 1, Sweight ≥ 1, SWC ≥ 1, SWHtR ≥ 1, SBMI ≥ 1, SAST ≥ 1, and STG ≥ 1 increased the statistical risk of childhood hypertension (odds ratio values (95% CI) were 3.70 (2.22-6.16), 2.58 (1.50-4.43), 3.08 (1.84-5.15), 2.33 (1.38-3.93), 2.96 (1.72-5.29), 2.38 (1.41-4.70), and 2.40 (1.38-4.19), respectively). The area under the ROC curve (AUC) for CLAP was higher than that for weight, WC, WHtR, BMI, AST, and TG in the prediction of hypertension. In conclusion, this study showed that CLAP is a novel indicator associated with hypertension in children and adolescents and can more effectively predict childhood hypertension than weight, WC, WHtR, BMI, AST, and TG can.

To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of chalcone-O-carbamate derivatives was designed and synthesized based on the multitarget-directed ligands strategy. The in vitro biological activities were evaluated including AChE/BChE inhibition, MAO-A/MAO-B inhibition, antioxidant activities, Aβ

Alternanthera philoxeroides recently expanded its range northwards in China. It is unknown if the range expansion has a genetic and/or epigenetic basis, or merely an environmental basis due to a warming climate. To test these possibilities, we used an RNAseq approach with a common greenhouse design to examine gene expression in individuals from the northern edge and central portion of alligator weed range from China to determine if there were differences in their responses to cold temperatures. We hypothesized that if the recent range expansion was primarily environmental, we would observe few differences or only differences unrelated to low-temperature adaptations. We assembled over 75,000 genes of which over 65,000 had long open reading frames with similarity to sequences from arabidopsis. Differences in expression between northern and southern populations that were both exposed to low temperatures showed similar expression among genes in the C-REPEAT/DRE BINDING FACTOR (CBF) regulon. However, gene set and sub-network enrichment analysis indicated differences in the response of photosynthetic processes and oxidative stress responses were different between the two populations and we relate these differences to cold adaptation. The transcriptome differences in response to cold between the individuals from the two populations is consistent with adaptations potentiating or resulting from selection after expansion into colder environments and may indicate that genetic changes have accompanied the recent northward expansion of A. philoxeroides in China. However, we cannot rule out the possibility of epigenetic changes may have a role in this expansion.

The multi-target-directed ligands have been regarded as the promising multifunctional agents for the treatment of Alzheimer’s disease (AD). Based on our previous work, a series of genistein-O-alkylamines derivatives was developed to further explore the structure-activity-relationship. The results showed that compound 7d indicated reversible and highly selective hAChE inhibitory activity with IC50 value of 0.53 μM. Compound 7d also displayed good antioxidant activity (ORAC = 1.1 eq.), promising neuroprotective effect and selective metal chelation property. Moreover, compound 7d significantly inhibited self-induced, hAChE-induced and Cu2+-induced Aβ aggregation with 39.8%, 42.1% and 74.1%, respectively, and disaggregated Cu2+-induced Aβ1-42 aggregation (67.3%). In addition, compound 7d was a potential autophagy inducer and improved the levels of GPX4 protein. Furthermore, compound 7d presented good blood-brain-barrier permeability in vitro. More importantly, compound 7d did not show any acute toxicity at doses of up to 1000 mg/kg and presented good precognitive effect on scopolamine-induced memory impairment. Therefore, compound 7d was a promising multifunctional agent for the development of anti-AD drugs.

Two new flavonoids (1 and 2), named 4′,7-dihydroxy-5-hydroxymethyl-8-prenylflavonoid and 4′,7-dihydroxy-5-hydroxymethyl-6,8-diprenylflavonoid, together with seven known flavonoids (3–9) were isolated from the aerial parts of Capsella bursa-pastoris (L.) Medik., Brassicaceae, for the first time. The chemical structures of the purified compounds (1–9) were identified by their spectroscopic data and references. Moreover, compounds (1–9) were evaluated for their hepatoprotective activities against d-galactosamine induced toxicity in WB-F344 cells by using a MTT colorimetric method. As a result, compounds 2, 3, 6, and 9 (10 μM) exhibited moderate hepatoprotective activities. Keywords: 5-Hydroxymethyl flavonoid, NMR, HR-ESI-MS, Spectral data, In vitro, Hepatoprotective activity

A Cp*CoIII-catalyzed C2-selective C–H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2′,1′:2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-ium by NaBH4.

A copper/iodine cocatalyzed decarboxylative cyclization of α-amino acids is described. Starting from the readily available amino acids and either 2-benzoylpyridines or 2-benzoylquinolines, 1,3-disubstituted imidazo[1,5-a]pyridines and 1,3-disubstituted imidazo[1,5-a]quinolines were prepared in excellent yields.

A silver-catalyzed sequential formation of two C–C bonds for the construction of a series of polysubstituted quinolines from anilines, aldehydes, and alcohols under mild conditions has been developed. The transformation is effective for a broad range of substrates, including aliphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol, thereby permitting the expansion of the constituent architectures of the heterocyclic framework.

A rhodium-catalyzed/copper-mediated tandem C(sp(2))-H alkynylation and intramolecular annulation of 2H-[1,2'-bipyridin]-2-ones with propargyl alcohols for the synthesis of 11-acylated imidazo[1,2-a:3,4-a']dipyridin-5-ium-4-olates is described.

Four β-cyclodextrin/4,4′-diphenylmethane diisocyanate/polyethylene glycol (β-CD/MDI/PEG) crosslinking copolymers with different crosslinking density were prepared and characterized as novel polymeric solid–solid phase change materials (SSPCMs) for thermal energy storage. In the SSPCMs, PEG acts as the phase change functional chain and β-cyclodextrin (β-CD) acts as the molecular framework. The results from wide-angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM) show that the synthesized SSPCMs have good crystallization properties and spherocrystal morphology with smaller size than that of PEG. According to the results of differential scanning calorimetry (DSC) and thermogravimetry (TG) curves, the SSPCMs possess high phase change enthalpies, good reusability, thermal reliability and stability. It is concluded that the crosslinking density of SSPCMs is a crucial factor significantly influenced the free movement and crystallization of PEG segments, and then affects phase transition properties of SSPCMs.

A series of novel polymeric solid–solid phase change materials (SSPCMs) with polyurethaneurea (PUU) copolymer structure were synthesized by the crosslinking copolymerization of polyethylene glycol (PEG) and multiamino compounds (diethylenetriamine, triethylenetetramine, tetraethylenepentamine) with different molar ratios. The results from the polarization optical microscopy (POM) and WAXD patterns indicate that the SSPCMs have typical spherocrystal morphology and characteristic diffraction peaks like neat PEG, but their spherulite size and diffraction peak intensity are smaller than those of PEG. According to the thermal analyses, the SSPCMs possess high phase transition enthalpies, good reusability and high thermal stability for their potential applications in thermal energy storage. With the decrease of crosslinking density of SSPCMs, the crystalline properties and thermal properties of SSPCMs have improved apparently, which is closely related to the free movement of PEG segments in the SSPCMs.

A silver-catalyzed formation of C–C bond for the construction of a series of polysubstituted quinolines from arylamines, aldehydes, and ketones or arylamines and 1,3-diketones has been developed. The transformation is effective for a broad range of substrates, thus enabling the expansion of constituent architectures on the heterocyclic framework. This use of a single catalytic system to mediate chemical transformations in a synthetic operation is important for the development of new atom-economic strategies and this strategy is efficient in building complex structures from simple starting materials in an environmentally benign fashion.

Alternanthera philoxeroides recently expanded its range northwards in China. It is unknown if the range expansion has a genetic and/or epigenetic basis, or merely an environmental basis due to a warming climate. To test these possibilities, we used an RNAseq approach with a common greenhouse design to examine gene expression in individuals from the northern edge and central portion of alligator weed range from China to determine if there were differences in their responses to cold temperatures. We hypothesized that if the recent range expansion was primarily environmental, we would observe few differences or only differences unrelated to low-temperature adaptations. We assembled over 75,000 genes of which over 65,000 had long open reading frames with similarity to sequences from arabidopsis. Differences in expression between northern and southern populations that were both exposed to low temperatures showed similar expression among genes in the C-REPEAT/DRE BINDING FACTOR (CBF) regulon. However, gene set and sub-network enrichment analysis indicated differences in the response of photosynthetic processes and oxidative stress responses were different between the two populations and we relate these differences to cold adaptation. The transcriptome differences in response to cold between the individuals from the two populations is consistent with adaptations potentiating or resulting from selection after expansion into colder environments and may indicate that genetic changes have accompanied the recent northward expansion of A. philoxeroides in China. However, we cannot rule out the possibility of epigenetic changes may have a role in this expansion.

An electrochemical Hofmann rearrangement is reported. With the mediation of NaBr, highly corrosive and toxic halogens are avoided. Moreover, this efficient and green approach is well compatible with a broad range of amides, including several commercial medicine derivatives, and provides direct access to synthetically useful carbamates. The synthetic utility of this method is also demonstrated by the preparation of 15N labeling carbamate and gram-scale synthesis of Amantadine.

Three kinds of new polymeric SSPCMs with different crosslinking structures were synthesized and characterized for thermal energy storage. In the SSPCMs, three hexahydroxy compounds (sorbitol, dipentaerythritol and inositol) were individually employed as the molecular skeleton and polyethylene glycol (PEG) was used as the phase change functional chain. The molecular structure, crystalline properties, phase change behaviors, thermal reliability and stability of the synthesized SSPCMs were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetry (TG), respectively. The results show that the prepared SSPCMs possess high thermal energy storage density and an applicable temperature range of 30–70 °C, and the maximum phase change enthalpy in the heating and cooling process for the SSPCMs is 107.5 kJ/kg and 102.9 kJ/kg, respectively. The prepared SSPCMs have good reusability, excellent thermal reliability and stability from the heating-cooling thermal cycle test and TG curves. The resultant SSPCMs could be potentially applied in the areas of thermal energy storage and temperature-control.

Graphene was modified with cobalt tetramethoxyphenylporphyrin (CoTPP) by an ultrasonic treatment and was used as a non-noble catalyst for oxygen reduction reaction (ORR) in neutral media. The resulting CoTPP–graphene was characterized by scanning electron microscopy (SEM), UV–vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy, which confirmed that CoTPP could be strongly supported onto graphene through π–π interaction. The electrochemical activity of CoTPP–graphene towards ORR was evaluated by cyclic voltammogram (CV). The CV results suggested the excellent catalytic activity of CoTPP–graphene in neutral electrolytes. Compared to electrodes modified with the mechanical mixture of graphene and CoTPP (N-CoTPP–graphene), the peak potential of ORR detected at the CoTPP–graphene electrode was more positive and the peak current was much higher, implying the necessary of ultrasonic and the enhanced activity of CoTPP after adsorbing on graphene surface. Thus, the CoTPP–graphene can be used as a good catalyst for ORR.

This study deals with the preparation and characterization of the composites of polyethylene glycol (PEG)/the synthesized polymeric solid-solid phase change material (SSPCM) as novel form stable phase change material (FSPCM) for thermal energy storage. The synthesized SSPCM can play two roles in the FSPCM: the supporting material and the phase change working substance. The influence of PEG content on crystalline properties and phase change behaviors of the FSPCMs was investigated. The polarizing optical microscopy (POM) images of FSPCMs show that all FSPCMs have the spherocrystal morphology, and the spherocrystal size of SSPCM increases with the increasing of PEG percent. The results from differential scanning calorimetry (DSC) indicate that the prepared FSPCMs with different PEG contents have high thermal storage density, and the enthalpy efficiency of them is much higher than that of the traditional FSPCMs due to the synergistic phase change effect of PEG and SSPCM. The Fourier transform infrared spectroscopy (FTIR) spectrum and DSC curve of the FSPCMs after thermal cycling are almost the same as those of the original samples, which indicates that the FSPCMs have excellent thermal reliability and reusability. The work not only supplied a kind of novel FSPCMs with high performances, but also proposed a new way to solve the problem of enthalpy decline of traditional FSPCMs and synthesized polymeric SSPCMs compared with solid-liquid PCMs.

A practical, electrochemical method is developed for the direct dehydrogenative lactonization of C(sp

Two new carbazole alkaloids 1 and 2, and eleven known congeners 3-13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1-13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC50 values of 12.1 (C.I. 8.2-15.2), 58.1 (C.I. 56.3-63.4), 13.7 (C.I. 9.2-15.4), 16.0 (C.I. 9.5-16.4), and 63.2 (C.I. 57.8-65.7) μM, respectively. Moreover, the antiangiogenic activities of compounds 1-13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1, 2, 6, 8, and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes.

A new phenylpropanoid glycoside, named α-L-rhamnopyranosyl-(1↔2)-β-D-[4″-(8E)-7-(3,4-dihydroxyphenyl)-8-propenoate, 1″-O-(7S)-7-(3,4-dihydroxyphenyl)-7-methoxy-ethyl]-glucopyranoside (1), together with nine known compounds (2–10) were isolated from the active fraction (n-Butanol fraction) of Gynura cusimbua for the first time. The known compounds (2–10) were identified as phenylpropanoid glycosides on the basis of extensive spectral data and references. The antiangiogenic activities of compounds (1–10) were evaluated by MTT assay on HUVECs and wild-type zebrafish in vivo model assay. As a result, compounds 1, 6, 7, 8 and 10 exhibited certain antiangiogenic activities.

A series of 2-acetyl-5-O-(amino-alkyl)phenol derivatives was designed, synthesized and evaluated as multi-function inhibitors for the treatment of Alzheimer’s disease (AD). The results revealed that compound TM-3 indicated selective AChE inhibitory potency (eeAChE, IC50 = 0.69 μM, selective index (SI) = 32.7). Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-3 could simultaneously bind to the catalytic active site and peripheral anionic site of AChE. And TM-3 was also a highly selective MAO-B inhibitor (IC50 = 6.8 μM). Moreover, TM-3 could act as antioxidant (ORAC value was 1.5eq) and neuroprotectant, as well as a selective metal chelating agent. More interestingly, compound TM-3 could cross the blood-brain barrier (BBB) in vitro and abided by Lipinski’s rule of five. Therefore, compound TM-3, a promising multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against AD.