Tourism experiences reduce the risk of cognitive impairment in the Chinese older adult: a prospective cohort study.

Background: Given the etiological complexity of cognitive impairment, no effective cure currently exists for precise treatment of dementia. Although scholars have noted tourism's potential role in managing cognitive impairment and mild dementia, more robust empirical investigation is needed in this area. This study aimed to examine the associations between tourism and cognitive impairment and dementia in older Chinese adults. Method: From a nationwide community-based cohort, 6,717 individuals aged ≥60 were recruited from 2011 to 2014, of whom 669 (9.96%) had had at least one tourism experience in the 2 years prior to enrollment. All the participants were then prospectively followed up until 2018. The association between tourism and cognitive impairment was examined by the Cox proportional hazards regression model. The adjusted hazard ratio (aHR) and its 95% confidence interval (CI) were calculated to evaluate the effect of tourism experience on cognitive impairment and dementia. Results: A total of 1,416 individuals were newly diagnosed with cognitive impairment and 139 individuals with dementia onset during follow-up. The incidence of cognitive impairment was significantly lower among participants with tourism experiences (316.94 per 10,000 person-years) than those without such experiences (552.38 per 10,000 person-years). Cox regression showed that tourism decreased the risk of cognitive impairment (aHR = 0.69, 95% CI: 0.41-0.62) when adjusted for behavioral covariates and characteristics. Compared with participants without tourism experiences, those with 1, 2, and ≥3 tourism experiences had a lower risk of cognitive impairment with the aHRs of 0.72 (95% CI: 0.52-0.99), 0.65 (0.42-1.01), and 0.68 (0.44-0.98), respectively. Tourism experiences also reduced participants' risk of dementia (aHR = 0.41, 95% CI: 0.19-0.89). Conclusion: Our findings demonstrated associations between tourism and reduced risks of cognitive impairment and dementia in older Chinese adults. Thus, tourism could serve as a novel approach to dementia prevention.

Applications of CRISPR screening to lung cancer treatment.

Lung cancer is an extremely aggressive and highly prevalent disease worldwide, and it is one of the leading causes of cancer death. Deciphering intrinsic genetic mechanism, finding new targets, and overcoming drug resistance are the key to lung cancer treatment. High-throughput CRISPR screening has been extensively used to obtain the genes related to cancers including lung cancer. This review describes CRISPR/Cas9 or CRISPR/dCas9-based technologies for high-throughput screening. We summarize the applications of CRISPR screening technology in exploring the mechanism of lung cancer development in vivo or in vitro, overcoming drug resistance, improving the effect of immunotherapy, and discovering new therapeutic targets. This review highlights the potential of CRISPR screening in combination with tumor barcoding and high-throughput sequencing (Tuba-seq) to precisely quantify the impact of alterations in many tumor suppressor genes on lung cancer.

First report of Bougainvillea spectabilis Willd bacterial leaf spot caused by Pantoea stewartii subspecies indologenes in China.

Bougainvillea spectabilis Willd. is an important ornamental flowering plant belonging to the family Nyctaginaceae. It is widely used in landscape designs in tropical and subtropical regions. In December 2020, severe disease-causing leaf spots were discovered on the leaves of B. spectabilis in the Modern Agricultural Park (110°19' E, 21°26' N) Zhanjiang City, Guangdong Province, China. Field surveys revealed that the disease was widespread, with an incidence of 60-80%. Early symptoms on the leaves appeared as tiny leaf spots that later developed into concentric circles surrounded by a yellowish halo (Fig. 1). Diseased leaves with typical symptoms were collected for pathogen isolation. The leading edges of the lesions were excised, sanitized in 75% ethanol for 30 s and in 3% sodium hypochlorite for 3 min, and rinsed three times with sterile distilled water (SDW). The diseased tissue was crushed in 1 mL SDW, soaked for 15 min, and then spread onto nutrient agar medium on a petri dish. Circular, bright yellow colonies with smooth margins were observed after 24 h of incubation at 28 °C. The isolate (SJM1) was a gram-negative bacillus with positive results for catalase, indole synthesis, maltose, and arbutin and negative results for sorbitol, lactose, salicin, and starch hydrolysis. The SJM1 genomic DNA was extracted using the TIANamp Bacterial DNA Kit, and partial 16S rDNA gene segments were amplified using the bacterial generic primers 27F and 1492R. The collated 16S rDNA gene sequences were submitted to the NCBI GenBank (MZ723935). BLAST analysis of the sequences revealed 99.38% identity with Pantoea stewartii (MG517424.1). Amplification using subspecies-specific primers galE (#562/564; Gehring et al. 2014), glmS (#356/341; Wensing et al. 2010), and pstC + pstS (#338/339; Wensing et al. 2010) revealed that the genes showed 99-100% identity with P. stewartii subsp. indologenes (galE = 100%, MZ754494.1; glmS = 99.79%, MZ75496.1; and pstC + pstS = 99.89%, MZ754495.1). Phylogenetic trees were constructed using the neighbor-joining method (MEGA X), with both the 16S rDNA sequence (Fig. 2 2A) and the concatenated 16S rDNA, galE, pstC + pstS, and glmS sequences (Fig.2 2B). The SJM1 isolate belonged to the same clade as P. stewartii subsp. indologenes and was 99% homologous to P. stewartii subsp. indologenes strain ZJ-FGZX1 (Fig. 2 2B; Ren et al. 2020). Pathogenicity tests were performed through prick wound inoculation. Sterile needles were used to create fresh wounds on healthy young leaves of one-year-old B. spectabilis plants. Wounds were inoculated with 20 µl bacterial suspension (1 × 108 CFU/ml) or SDW. Four leaves per plant and three plants per treatment were evaluated. The plants were incubated at 28 °C temperature and 80-90% relative humidity. After 4-7 days of inoculation, all plants inoculated with the bacterial suspension had spot symptoms with a halo, similar to those observed in the field. However, leaves inoculated with SDW alone did not show any symptoms. Furthermore, the colony morphology and 16S rDNA sequences of the strains isolated from the inoculated leaves were identical to those of the original isolates. These results verified Koch's postulates. Based on biochemical identification and sequencing analysis, the pathogen causing B. spectabilis leaf spot was identified as P. stewartii subsp. indologenes. Previous reports have shown that P. stewartii subsp. indologenes can cause diseases in Dracaena sanderiana, Cenchrus americanus, and Allium cepa (Zhang et al. 2020, Ashajyothi et al. 2021, Stumpf et al. 2018). To our knowledge, this is the first report of P. stewartii subsp. indologenes causing B. spectabilis leaf spot disease in China.

Chiral Naphthyl-C2-Indole as Scaffold for Phosphine Organocatalysis: Application in Asymmetric Formal [4 + 2] Cycloaddition Reactions.

The applications of a newly designed chiral naphthyl-C2-indole bifunctional phosphine organocatalyst in stereoselective formal [4 + 2] cycloaddition reactions were reported. The chiral naphthyl-C2-indole skeleton was introduced to bifunctional phosphine organocatalysis for the first time, and excellent stereocontrol was achieved in two types of formal [4 + 2] cycloaddition reactions. With the optimal catalyst, a series of chiral spirooxindole and hydrodibenzofuran architectures were produced in moderate to good yields with excellent stereoselectivities (up to >99% ee, >20:1 dr).

Fast determination of isomeric triterpenic acids in Osmanthus fragrans (Thunb.) Lour. fruits by UHPLC coupled with triple quadrupole mass spectrometry.

Triterpenic acids possess rich biological activity. Due to slight differences in structure and polarity, the simultaneous determination of isomeric triterpenic acids is challenging. In the present work, a simple and effective approach to chromatographic separation of such compounds based on conventional C18 stationary phase with gradient elution was developed, which allowed the simultaneous separation of eleven analytes including euscaphic, arjunic, tormentic, arjunolic, asiatic, pomolic, maslinic, corosolic, oleanolic, ursolic and 2-Epi tormentic acid (internal standard). This approach with mass spectrometric detection and ultrasonic extraction was fast, sensitive and accurate for analyzing isomeric triterpenic acids in O. fragrans fruits with a toal duration of the analytical cycle (including pretreatment) within one hour. The LODs lie in ranges of 0.8-12 ng/mL (30 ng/mL for asiatic and corosolic acid). The developed method was validated and successfully applied in ten batches of O. fragrans fruits, which could reflect the detail content difference of triterpenic acid components.

Organocatalytic Enantioselective γ-Elimination: Applications in the Preparation of Chiral Peroxides and Epoxides.

An organocatalyzed enantioselective γ-elimination process has been achieved and applied in the kinetic resolution of peroxides to access chiral peroxides and epoxides. The reaction provided a pathway for the preparation of two useful synthetic and biologically important structural motifs through a single-step reaction. A range of substrates has been resolved with a selectivity factor up to 63. The obtained enantioenriched peroxides and epoxides allowed a series of transformations with retained optical purities.

A HPLC-MS method for profiling triterpenoid acids and triterpenoid esters in Osmanthus fragrans fruits.

Triterpenoids, as an important family of plant secondary metabolites, have important biological activities associated with health and disease prevention. In this work, we proposed a HPLC-MS method for profiling multiple groups of triterpenoid acids and triterpenoid esters differing only in one position of the hydroxyl or methyl group in O. fragrans fruits. A total of thirty-one compounds were identified, and twenty-seven components were discovered in O. fragrans fruits for the first time. The HPLC-MS profiling method was applied in the analysis of the triterpenoids of O. fragrans flowers, and the time courses of triterpenoids of O. fragrans fruits.

Organocatalytic Enantioselective Selenosulfonylation of a C-C Double Bond To Form Two Stereogenic Centers in an Aqueous Medium.

Organocatalytic selenosulfonylation of the C-C double bond of α,ß-unsaturated ketones to construct two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl and ß-sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivities with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to a decagram scale via a simple workup procedure.

Metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM).

A metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM) was described herein. The reaction was conducted under mild conditions without any catalysts or additives. Preliminary mechanism studies revealed that the formation of VQM was the key for this alkyne di-functionalization reaction. The reaction could be applied in the enantioselective asymmetric synthesis of axially chiral styrene. Furthermore, the selenosulfonylation adducts can be transformed into useful naphtho[2,1-b]furan and benzofuran scaffolds.

Organocatalytic Asymmetric Atroposelective Construction of Axially Chiral 1,4-Distyrene 2,3-Naphthalene Diols.

An efficient organocatalytic construction of enantioenriched axially chiral 1,4-distyrene 2,3-naphthalene diols through the nucleophilic addition of α-amido sulfone to in situ generated vinylidene o-quinone methide is described. The reaction pathway was investigated by isolating reaction intermediates and performing a kinetic resolution process. Axially chiral 1,4-distyrene 2,3-naphthalene diol was used as the chiral ligand for the enantioselective addition of diethylzinc to naphthalene formaldehyde. The preliminary results revealed that these adducts could be potentially used as ligands in asymmetric synthesis.

Enantioselective Construction of Vicinal Diaxial Styrenes and Multiaxis System via Organocatalysis.

A highly diastereo- and enantioselective methodology for the asymmetric synthesis of vicinal diaxial styrenes and multiaxis system was achieved by organocatalysis. Various vicinal diaxial styrenes and multiaxis systems were obtained in excellent enantioselective manners. The mechanism studies revealed that a new tetra-substituted vinylidene ortho-quinone methide (VQM) intermediate was likely involved and accounted for the excellent enantioselectivity.

Determination of three phenylethanoid glycosides in Osmanthus fragrans fruits by high-performance liquid chromatography with fluorescence detection.

A simple and sensitive high-performance liquid chromatography with fluorescence detection method has been developed for the determination of active components in Osmanthus fragrans fruits. In this work, reversed-phase liquid chromatography with a C18 column and mobile phase of methanol/water were applied to effectively separate three phenylethanoid glycosides, including salidroside, neonuezhenide, and nuezhenide. The limits of detection of salidroside, neonuezhenide, and nuezhenide were 3.9, 25.4, and 24.2 ng/mL respectively. Then this method was applied to determine the contents in several batches of O. fragrans fruits extract, which were collected from Wuhan, Hefei, and Changsha. Meanwhile, the method was used for the detection of rat plasma administrated with O. fragrans fruits extract, which could be an alternative method applied to the field of pharmacokinetics study in future. The results implied that the developed method was economical, simple, convenient, and sensitive, which was appropriate for the determination of salidroside, neonuezhenide, and nuezhenide in O. fragrans fruits.

Identification and Quantitation of the Bioactive Components in Osmanthus fragrans Fruits by HPLC-ESI-MS/MS.

Information on the chemical composition of Osmanthus fragrans fruits is still limited because there are many compounds present in low concentrations in the plant. In this work, the bioactive components in O. fragrans fruit extract were investigated by a new high-performance liquid chromatography electrospray ionization tandem mass spectrometry method, which allows sensitive analysis both in identification and quantitation. A total of 28 compounds were tentatively identified, and 16 components were discovered in O. fragrans fruits for the first time. The validated quantitative methods for the determination of the bioactive components were subsequently applied to analyze batches of O. fragrans fruits from different cultivars, which is beneficial for the comprehensive utilization of O. fragrans fruits.