Catalytic Asymmetric Construction of α,α-Diaryl Aldehydes via Oxo-Hydroarylation of Terminal Alkynes.

Chiral aldehydes containing a tertiary stereogenic center are versatile building blocks in organic chemistry. In particular, such structural motifs bearing an α,α-diaryl moiety are very challenging scaffolds and their efficient asymmetric synthesis is not reported. In this work, a phosphoric acid-catalyzed enantioselective synthesis of α,α-diaryl aldehydes from simple terminal alkynes is presented. This approach yields a wide range of highly enolizable α,α-diaryl aldehydes in good yields with excellent enantioselectivities. Facile transformations of the products, as well as an efficient synthesis of bioactive molecules, including an effective anti-smallpox agent and an FDA-approved antidepressant drug (+)-sertraline, are demonstrated.

Copper-catalyzed atroposelective synthesis of C-O axially chiral compounds enabled by chiral 1,8-naphthyridine based ligands.

Axially chiral molecular scaffolds are widely present in therapeutic agents, natural products, catalysts, and advanced materials. The construction of such molecules has garnered significant attention from academia and industry. The catalytic asymmetric synthesis of axially chiral biaryls, along with other non-biaryl axially chiral molecules, has been extensively explored in the past decade. However, the atroposelective synthesis of C-O axial chirality remains largely underdeveloped. Herein, we document a copper-catalyzed atroposelective construction of C-O axially chiral compounds using novel 1,8-naphthyridine-based chiral ligands. Mechanistic investigations have provided good evidence in support of a mechanism involving synergistic interplay between a desymmetrization reaction and kinetic resolution process. The method described in this study holds great significance for the atroposelective synthesis of C-O axially chiral compounds, with promising applications in organic chemistry. The utilization of 1,8-naphthyridine-based ligands in copper catalysis is anticipated to find broad applications in asymmetric copper(i)-catalyzed azide-alkyne cycloadditions (CuAACs) and beyond.

Electrochemical Synthesis of C(sp3)-Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds.

Alkylamines form the backbone of countless nitrogen-containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three-dimensional α-substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst-free electroreductive manifold that merges amines, carbonyl compounds and carbon-based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α-amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug-like scaffolds which are inaccessible by conventional means.

Amplifying chlorinated phenol decomposition via Dual-Pathway O2 Activation: The impact of zirconium loading on BiOCl.

The effectiveness of photocatalytic molecular oxygen (O2) activation in pollutant removal relies on the targeted production of reactive oxygen species (ROS). Herein, we demonstrate the dual-pathway activation of O2 on BiOCl through zirconium (Zr) loading. The incorporation of Zr onto the surface of BiOCl not only leads to an increased generation of oxygen vacancies (OV) but also fosters a coupling between the d electrons of Zr and OV, forming dual-active sites known as Zr-oxygen vacancies (Zr-OV). Generally, OV adsorbs O2 and transfers one electron directly to form superoxide radicals (•O2-). Contrary to the conventional single-electron direct activation of O2 to form •O2-, Zr-OV exhibits more flexible coordination and superior electron-donating capabilities. It facilitates O2 conversion to peroxide radicals (O22-) and enables the subsequent generation of •O2- from O22-, significantly promotes the dechlorination and mineralization efficiency of chlorophenol under visible light. This study presents a straightforward strategy to precisely regulate ROS production by expanding pathways, shedding light on the critical role of managing ROS generation for effective pollutant purification.

Enantioselective Copper-Catalyzed Ring-Opening Diboration of Arylidenecyclopropanes to Access Chiral Skipped 1,4- and 1,3-Diboronates.

Two enantioselective approaches to synthesize chiral skipped diboronate compounds have been developed, relying on copper-catalyzed one-pot asymmetric ring-opening diboration of arylidenecyclopropanes. A wide range of arylidenecyclopropanes react smoothly with HBpin in the presence of CuOAc and (R)-DTBM-Segphos, affording chiral 1,4-diboronates with high enantioselectivity (up to 99% ee). Meanwhile, a variety of arylidenecyclopropanes react selectively with HBpin and B2pin2 in the presence of CuOAc and (S,S)-Ph-BPE with the sequential addition of MeOH, providing chiral 1,3-diboronates with high enantioselectivity (up to 98% ee). These enantioenriched 1,3- and 1,4-diboronates can undergo various enantiospecific transformations with minimal loss of their enantiopurity. Mechanistic studies reveal that these two diboration processes start with CuH-catalyzed ring-opening hydroboration of arylidenecyclopropanes to form a mixture of Z/E-homoallyl boronate intermediates, which subsequently undergo enantioselective CuH-catalyzed second hydroboration or Cu-Bpin-catalyzed protoboration to produce chiral 1,4-diboronates or 1,3-diboronates, respectively.

A rapid multispectral endoscopic imaging system for in vivo assessment of the morphological and physiological characteristics of mouse intestines.

Accurate assessment of blood content in biological tissues is critical for the diagnosis and monitoring of various diseases, including cardiovascular disease, tumors, trauma, and the success rate of organ transplants. In this study, a multispectral endoscopic imaging system was built for capturing tissue reflection optical images in 18 bands across the wavelength range from 400 nm to 760 nm, non-invasively. The system was characterized by six tri-channel narrowband filters installed in front of the light source to achieve spectral separation and was equipped with a specially designed color CCD for achieving a speed of 24 multispectral imaging cubes per second. A method based on linear matrix inversion was proposed to calibrate the CCD spectral response overlaps, while a spectral analysis algorithm was developed for evaluating blood content and detecting tissue composition. The developed system was implemented in an in vivo mouse model for illustrating the blood volume, blood oxygen saturation index, and scattering particle size of the intestinal wall mucosa. The observations not only helped us to understand the blood supply situation in the intestinal mucosa, but also further testified the feasibility of our presented system. Meanwhile, the developed system could provide critical non-invasive optical information for intracavitary cancer diagnosis, surgery guidance, and treatment assessment.

Molecular Editing of Pyrroles via a Skeletal Recasting Strategy.

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization strategies allow for peripheral modifications of heterocyclic motifs, often being specific and taking place at multiple sites. The past few years have seen the quick emergence of exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion and structural diversification, as well as scaffold hopping. The construction of heterocycles via deconstruction of simple heterocycles is unknown. Herein, we disclose a new molecular editing method which we name the skeletal recasting strategy. Specifically, by tapping on the 1,3-dipolar property of azoalkenes, we recast simple pyrroles to fully substituted pyrroles, through a simple phosphoric acid-promoted one-pot reaction consisting of dearomative deconstruction and rearomative reconstruction steps. The reaction allows for easy access to synthetically challenging tetra-substituted pyrroles which are otherwise difficult to synthesize. Furthermore, we construct N-N axial chirality on our pyrrole products, as well as accomplish a facile synthesis of the anticancer drug, Sutent. The potential application of this method to other heterocycles has also been demonstrated.

Effects of Trichinella spiralis and its serine protease inhibitors on autophagy of host small intestinal cells.

In eukaryotes, autophagy is induced as an innate defense mechanism against pathogenic microorganisms by self-degradation. Although trichinellosis is a foodborne zoonotic disease, there are few reports on the interplay between Trichinella spiralissurvival strategies and autophagy-mediated host defense. Therefore, this study focused on the association between T. spiralis and autophagy of host small intestinal cells. In this study, the autophagy-related indexes of host small intestinal cells after T. spiralis infection were detected using transmission electron microscopy, hematoxylin and eosin staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting. The results showed that autophagosomes and autolysosomes were formed in small intestinal cells, intestinal villi appeared edema, epithelial compactness was decreased, microtubule-associated protein 1A/1B-light chain 3B (LC3B) was expressed in lamina propria stromal cells of small intestine, and the expression of autophagy-related genes and proteins was changed significantly, indicating that T. spiralis induced autophagy of host small intestinal cells. Then, the effect of T. spiralis on autophagy-related pathways was explored by Western blotting. The results showed that the expression of autophagy-related pathway proteins was changed, indicating that T. spiralis regulated autophagy by affecting autophagy-related pathways. Finally, the roles of T. spiralis serine protease inhibitors (TsSPIs), such as T. spiralis Kazal-type SPI (TsKaSPI) and T. spiralis Serpin-type SPI (TsAdSPI), were further discussed in vitro and in vivo experiments. The results revealed that TsSPIs induced autophagy by influencing autophagy-related pathways, and TsAdSPI has more advantages. Overall, our results indicated that T. spiralis induced autophagy of host small intestinal cells, and its TsSPIs play an important role in enhancing autophagy flux by affecting autophagy-related pathways. These findings lay a foundation for further exploring the pathogenesis of intestinal dysfunction of host after T. spiralis infection, and also provide some experimental and theoretical basis for the prevention and treatment of trichinellosis.

Exploring learning needs for community education among older adults from the perspective of active aging: a qualitative study in rural China.

Older adults are often excluded from the category of active learning populations in many cultures. However, Active Aging (AA) Framework highlights that regular participation of older adults in community education activities can enhance opportunities for social participation, thereby promoting successful aging within this demographic. This descriptive qualitative study aimed to explore the learning needs for community education among older adults in rural China from the perspective of active aging. Purposive sampling method and maximum difference sampling were used to recruit 18 participants aged 60 and over. Four core themes emerged from the analysis: the need for health knowledge, the need for participating in social activities, the need for social security knowledge, and the need for educational methods. The findings of this study confirm that older adults in a Chinese village setting have diverse learning needs for community education. Awareness of these needs can assist policy makers and healthcare workers in providing tailored curricula and intervention measures to meet their learning needs.

Enantioselective De Novo Synthesis of α,α-Diaryl Ketones from Alkynes.

Chiral α,α-diaryl ketones are structural motifs commonly present in bioactive molecules, and they are also valuable building blocks in synthetic organic chemistry. However, catalytic asymmetric synthesis of α,α-diaryl ketones bearing a tertiary stereogenic center remains largely unsolved. Herein, we report a catalytic de novo enantioselective synthesis of α,α-diaryl ketones from simple alkynes via chiral phosphoric acid (CPA) catalysis. A broad range of enolizable α,α-diaryl ketones are prepared in good yields and with excellent enantioselectivities. The described protocol also serves as an efficient deuteration method for the preparation of enantiomerically enriched deuterated α,α-diaryl ketones. Using the methodology reported, bioactive molecules, including one of the best-selling anti-breast cancer drugs, tamoxifen, are readily synthesized.

Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis.

The C-N axially chiral N-arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well as in chiral ligands/catalysts. Asymmetric synthesis of N-arylpyrroles, however, is still challenging, and the simultaneous creation of contiguous C-N axial and central chirality remains unknown. Herein, a diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. The key transformation is a one-pot, three-component oxo-diarylation reaction, which simultaneously creates a C-N axial chirality and a central quaternary stereogenic center. A broad range of unactivated alkynes were readily employed as a reaction partner in this transformation, and the N-arylpyrrole products are obtained in good yields, with excellent enantioselectivities and very good diastereoselectivities. Notably, the N-arylpyrrole skeletons represent interesting structural motifs that could be used as chiral ligands and catalysts in asymmetric catalysis.

Exosome-delivered miR-153 from Trichinella spiralis promotes apoptosis of intestinal epithelial cells by downregulating Bcl2.

Trichinellosis, a helminthic zoonosis, exhibits a cosmopolitan distribution and is a public health concern. In previous studies, it was reported that the exosomes secreted by Trichinella spiralis larvae (TsExos) largely affected cell biological activities. miRNAs, as exosome-delivered cargoes, affect the biological activities of the host by targeting genes. The present study aimed to elucidate the mechanisms by which miRNAs interact with intestinal epithelial cells. First, a miRNA library of TsExos was constructed; then, based on high-throughput miRNA sequencing results, miR-153 and its predicted target genes, namely, Agap2, Bcl2 and Pten, were selected for follow-up studies. The dual-luciferase reporter assays revealed that miR-153 directly targeted Bcl2 and Pten. Furthermore, real-time qPCR and Western blotting revealed that only Bcl2 was downregulated by TsExo-delivered miR-153 in porcine intestinal epithelial cells (IPEC-J2). Bcl2, an important antiapoptotic protein, plays an essential role in cell apoptosis as a common intersecting molecule of various signal transduction pathways. Therefore, we hypothesized that miR-153 derived from TsExos causes cell apoptosis by targeting Bcl2. The results suggested that miR-153 could induce apoptosis, reduce mitochondrial membrane potential, affect cell proliferation, and cause damage and substantial oxidative stress. Furthermore, miR-153 coincubated with IPEC-J2 cells stimulated the accumulation of the proapoptotic proteins Bax and Bad, which belong to the Bcl2 family of proteins, and the apoptosis-implementing proteins Caspase 9 and Caspase 3. Moreover, studies have suggested that miR-153 can promote apoptosis by regulating the MAPK and p53 signalling pathways involved in apoptosis. Thus, exosome-mediated miR-153 delivery secreted by T. spiralis could induce apoptosis and affect the MAPK and p53 signalling pathways by downregulating Bcl2 in IPEC-J2 cells. The study highlights the mechanisms underlying the invasion of T. spiralis larva.

Intervention effects of Trichinella spiralis excretory-secretory antigens on allergic asthma in mice.

Allergic asthma is a chronic, heterogeneous and inflammatory respiratory disease, and there are few medicines at present. An increasing number of studies indicate that Trichinella spiralis (T. spiralis) and its excretory-secretory (ES) antigens are inflammatory modulator. Therefore, this study focused on the effects of T. spiralis ES antigens on allergic asthma. Asthma model was established by sensitizing mice with ovalbumin antigen (OVA) and aluminum hydroxide (Al[OH]3), the asthmatic mice were interfered using T. spiralis 43 kDa protein (Ts43), T. spiralis 49 kDa protein (Ts49), and T. spiralis 53 kDa protein (Ts53), the important components of ES antigens, to establish ES antigens intervention models. Then, asthma symptom changes, weight changes, and lung inflammation of mice were evaluated. The results showed that ES antigens could relieve symptoms, weight loss, and lung inflammation caused by asthma in the mice, and the effect of combined intervention of Ts43, Ts49, and Ts53 was better. Finally, the effects of ES antigens on type 1 helper T (Th1) and type 2 helper T (Th2) immune responses, and the differentiation direction of T lymphocytes in mice were discussed by detecting Th1 and Th2 cell-related factors and the ratio of CD4+/CD8+ T cells. The results suggested that the ratio of CD4+/CD8+ T cells decreased and the ratio of Th1/Th2 cells increased. In conclusion, this study indicated that T. spiralis ES antigens could mitigate allergic asthma in the mice by changing the differentiation direction of CD4+ and CD8+ T cells and regulating the imbalance of Th1/Th2 cells ratio.

Modulation of long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression in the liver of Beagle dogs by Toxocara canis infection.

BACKGROUND: Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) play crucial roles in regulating various physiological and pathological processes. However, the role of lncRNAs and mRNAs in mediating the liver response during Toxocara canis infection remains incompletely understood. METHODS: In the present study, the expression profile of lncRNAs and mRNAs was investigated in the liver of Beagle dogs infected by T. canis using high-throughput RNA sequencing. RESULTS: Compared with the control groups, 876 differentially expressed (DE) lncRNAs and 288 DEmRNAs were identified at 12 h post-infection (hpi), 906 DElncRNAs and 261 DEmRNAs were identified at 24 hpi, and 876 DElncRNAs and 302 DEmRNAs were identified at 36 days post-infection (dpi). A total of 16 DEmRNAs (e.g. dpp4, crp and gnas) were commonly identified at the three infection stages. Enrichment and co-localization analyses identified several pathways involved in immune and inflammatory responses during T. canis infection. Some novel DElncRNAs, such as LNC_015756, LNC_011050 and LNC_011052, were also associated with immune and inflammatory responses. Also, LNC_005105 and LNC_005401 were associated with the secretion of anti-inflammatory cytokines, which may play a role in the healing of liver pathology at the late stage of infection. CONCLUSIONS: Our data provided new insight into the regulatory roles of lncRNAs and mRNAs in the pathogenesis of T. canis and improved our understanding of the contribution of lncRNAs and mRNAs to the immune and inflammatory response of the liver during T. canis infection.

A Reliable and Repeatable Model for Predicting Microvascular Invasion in Patients With Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: The reproducibility of imaging models for predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains questionable due to inconsistent interpretation of image signs. Our aim was to screen for high-consensus MRI features to develop a repeatable model for predicting MVI. MATERIALS AND METHODS: We included 219 patients with HCC who underwent surgical resection, and patients were divided into a training cohort (n = 145) and a validation cohort (n = 74). Morphological characteristics, signal features on hepatobiliary phases, and dynamic enhancement patterns were qualitatively interobserver evaluated. Interobserver agreement was assessed using Cohen's κ for selecting features with high interobserver agreement. Risk factors that were significant in stepwise multivariate analysis and that could be measured with good interobserver agreement were used to construct a predictive model, which was assessed in the validation cohort. The diagnostic performance of the model was evaluated based on area under the receiver operating characteristic curve (AUC). RESULTS: Multivariate analysis identified nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery as independent risk factors of MVI. These MRI-based features showed good or nearly perfect interobserver agreement between radiologists (κ > 0.6). The predictive model predicted MVI well in the training (AUC 0.734) and validation cohorts (AUC 0.759) and fitted well to calibration curves. CONCLUSION: MRI features included nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery that can be assessed with high interobserver agreement can predict MVI in HCC patients. The predictive model described here may be useful to radiologists, regardless of experience level.

A qualitative exploration of Chinese rural older adults' adaption experience to disability in Henan Province.

BACKGROUND: The global population is ageing in a serious way and the number of disabled elderly people is increasing. Disability is a combination of physical and functional impairments, activity limitations, and social participation restrictions that significantly affect the quality of life of older adults. This study used the Roy adaptation model to examine the adaptive strategies of rural disabled elderly. METHODS: An interview outline was prepared based on the Roy Adaptation Model, in-depth interviews were conducted with eligible rural elderly with disabilities using purposive sampling. Interview data were analyzed using the colaizzi method to obtain relevant themes and sub-themes of the adaptation experience. RESULTS: Fifteen eligible disabled elderly participated in the interview, with an average age of 73.7 years old, showing different adaptation experiences in different aspects, a total of 5 themes and 18 sub-themes were extracted: (a)physiological function adaptation: learning to monitor physiological indicators, active medical compliance behavior, active rehabilitation exercise, adjusting lifestyle and coping with failure, (b) self-concept adaptation: adjustment of gratitude mentality, self-consolation, transferring the attention, seeking emotional comfort, and negative emotional response, (c) role function adaptation: positive self-care role, negative family role and escape of social role, (d) interdependence adaptation: actively seeking support and complex social coping, and (e) adaptation influencing factors: personal factors, caregiver factors and the policy factors. CONCLUSIONS: The disabled elderly show different adaptation strategies in four ways, and are affected by personal factors, caregiver factors and policy factors. A multi-faceted support system for the disabled elderly is recommended, and the caregivers should be trained in all-round care knowledge and skills.

Synthesis of Axially Chiral CF3 -Substituted 2-Arylpyrroles by Sequential Phosphine-Catalyzed Asymmetric [3+2] Annulation and Oxidative Central-to-Axial Chirality Transfer.

A sequential phosphine-catalyzed asymmetric [3+2] annulation of aldimines with allenoates and oxidative central-to-axial chirality transfer strategy has been developed. This approach is operationally simple, allowing for rapid access to a range of axially chiral CF3 -containing 2-arylpyrroles with high enantiomeric excess. Furthermore, an atroposelective synthesis of esaxerenone is presented, illustrating the practical potential of the reported method.

Effects of exosomes derived from Trichinella spiralis infective larvae on intestinal epithelial barrier function.

Muscle larvae of Trichinella spiralis parasitize the host intestinal epithelium. The mechanisms of exosomes participating in the invasion of T. spiralis muscle larvae are unclear. Hence, the purpose of this study was to explore the effect of exosomes derived from T. spiralis infective larvae (TsExos) on the barrier function of porcine small intestinal epithelial cells (IPEC-J2). First, TsExos were successfully obtained, and their ingestion by epithelial cells was validated. Furthermore, the optimal induction condition was determined by the CCK8 kit, and we found that exposure to 150 µg/mL TsExos for 12/24 h decreased the viability of IPEC-J2 cells by 30%. Based on this outcome, the effects of TsExos on cell biological processes and tight junctions were studied. After coincubation of TsExos and IPEC-J2 cells, the results showed a significant increase in the content of FITC-dextran and in the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS). The rate of apoptosis increased by 12.57%, and nuclear pyknosis and nuclear rupture were observed. After the cells were induced by TsExos, the expression of IL-1 was upregulated, but the expression of IL-10, TGF-ß, TLR-5, MUC-1 and MUC-2 was downregulated. TsExo induction also led to a decrease in the levels of ZO-1, CLDN-3, and OCLN. In conclusion, TsExos are involved in several cellular biological processes, and they function by disrupting physiological and biochemical processes, hyperactivating innate immunity, and damaging tight junctions.

Asymmetric multifunctionalization of alkynes via photo-irradiated organocatalysis.

Alkynes represent a family of pivotal and sustainable feedstocks for various industries such as pharmaceuticals, agrochemicals, and materials, and they are widely used as important starting materials for the production of a broad range of chemical entities. Nevertheless, efficient structural elaborations of alkynes in chemical synthesis, especially asymmetric multifunctionalization of alkynes, remain largely unexplored. It is thus imperative to develop new asymmetric synthetic approaches, making use of these richly available chemical feedstocks, and enabling their conversion to value-added chiral molecules. Here, we disclose our findings on highly enantioselective multifunctionalization of alkynes by merging photochemistry and chiral phosphoric acid catalysis. Our reported one-pot synthetic protocol is applicable to all types of alkyne substrates, incorporating all three reactants in a fully atom-economic fashion to produce optically enriched tetrasubstituted triaryl- and diarylmethanes, important structural scaffolds in medicinal chemistry and biological sciences.

Nickel-Hydride-Catalyzed Diastereo- and Enantioselective Hydroalkylation of Cyclopropenes.

Cyclopropanes are structural motifs that are widely present in natural products and bioactive molecules, and they are also tremendously useful building blocks in synthetic organic chemistry. Asymmetric synthesis of cyclopropane derivatives has been an intensively researched area over the years, but efficient asymmetric preparation of alkylcyclopropane scaffolds remains a challenging topic. Herein, we report a nickel-hydride-catalyzed enantioselective and diastereoselective hydroalkylation of cyclopropenes for facile synthesis of chiral alkylcyclopropane motifs. The reported method is efficient and versatile, taking place under mild reaction conditions, and having broad applicability and excellent functional group tolerance.