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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.

Dietary and genetic factors are considered to be associated with UGI cancer risk. However, examinations of the effect of healthy diet on UGI cancer risk and the extent to which healthy diet modifies the impact of genetic susceptibility on UGI cancer remains limited. Associations were analyzed through Cox regression of the UK Biobank data (n = 415,589). Healthy diet, based on “healthy diet score,” was determined according to fruit, vegetables, grains, fish, and meat consumption. We compared adherence to healthy diet and the risk of UGI cancer. We also constructed a UGI polygenic risk score (UGI-PRS) to assess the combined effect of genetic risk and healthy diet. For the results high adherence to healthy diet reduced 24% UGI cancer risk (HR high-quality diet: 0.76 (0.62–0.93), p = 0.009). A combined effect of high genetic risk and unhealthy diet on UGI cancer risk was observed, with HR reaching 1.60 (1.20–2.13, p = 0.001). Among participants with high genetic risk, the absolute five-year incidence risk of UGI cancer was significantly reduced, from 0.16% to 0.10%, by having a healthy diet. In summary, healthy diet decreased UGI cancer risk, and individuals with high genetic risk can attenuate UGI cancer risk by adopting a healthy diet.

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

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

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.