Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.

Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery.

Metastasis contributes to the dismal prognosis of bladder cancer (BLCA). The mechanical status of the cell membrane is expected to mirror the ability of cell migration to promote cancer metastasis. However, the mechanical characteristics and underlying molecular profile associated with BLCA metastasis remain obscure. To study the unique cellular architecture and traits associated with cell migration, using a process called cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) we generated an aptamer-based molecular probe, termed spl3c, which identified cytoskeleton-associated protein 4 (CKAP4). CKAP4 was associated with tumor metastasis in BLCA, but we also found it to be a mechanical regulator of BLCA cells through the maintenance of a central-to-peripheral gradient of stiffness on the cell membrane. Notably, such mechanical traits were transportable through exosome-mediated intercellular CKAP4 trafficking, leading to significant enhancement of migration in recipient cells and, consequently, aggravating metastatic potential in vivo. Taken together, our study shows the robustness of this aptamer-based molecular tool for biomarker discovery, revealing the dominance of a CKAP4-induced central-to-peripheral gradient of membrane stiffness that benefits cell migration and delineating the role of exosomes in mediating mechanical signaling in BLCA metastasis.

MicroRNA-146a-5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma.

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.

Association of the m6 A reader IGF2BP3 with tumor progression and brain-specific metastasis in breast cancer.

BACKGROUND: This study aimed to determine the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an N6 -methyladinosine reader, in the progression and distant metastasis of breast cancer. METHODS: IGF2BP3 expression was assessed in 152 pairs of breast cancer and adjacent normal tissue (ANT) by real-time quantitative polymerase chain reaction and in 561 cases of breast cancer and 163 cases of ANT by immunohistochemistry. Survival curves were estimated using the Kaplan-Meier method and then compared statistically using the log-rank test. The prognostic role of IGF2BP3 was determined by Cox regression analysis. RESULTS: Analysis of public gene data sets revealed that IGF2PB3 predicted distant metastasis in breast cancer and was highly correlated with brain metastasis. In the clinical retrospective cohort, the positive rate of IGF2BP3 increased gradually with breast cancer progression. Positive IGF2BP3 expression was related to poor distant metastasis-free survival (DMFS, p = .030) and Cox regression analysis identified IGF2BP3 as an independent risk factor for DMFS (hazard ratio, 1.876; 95% confidence interval, 1.128-3.159; p = .019). Positive IGF2BP3 expression was markedly related to breast cancer brain metastasis (p = .011) but not to lung and bone metastasis. Moreover, patients with IGF2BP3-positive brain metastasis had lower survival than patients with IGF2BP3-negative brain metastasis (p = .041). Gene expression profiling results indicated that high IGF2BP3 expression was associated with the PD-1 checkpoint pathway, HER2-HER3 signaling, and epithelial-mesenchymal transition. CONCLUSIONS: IGF2BP3 may serve as a novel predictive biomarker and a potential therapeutic target for breast cancer brain metastasis, which warrants further investigation. PLAIN LANGUAGE SUMMARY: As an m6 A reader, IGF2BP3 is dysregulated and implicated in various cancers but its role in breast cancer has not been fully clarified. In this study, we found that IGF2BP3 was upregulated in breast cancer and IGF2BP3 expression increased gradually during breast cancer progression. IGF2BP3 expression exerted no effect on the overall survival and breast cancer-specific survival of breast cancer patients; however, IGF2BP3-positive patients were more likely to develop distant metastasis than IGF2BP3-negative patients. In addition, IGF2BP3 was associated with brain-specific metastasis in breast cancer patients. These findings warrant further investigation because they provide a rationale for novel predictive or therapeutic approaches.

Engineering High-Tortuosity 3D Gradient Structure and CFD-Assisted Multifield Analysis for Solar Interfacial Evaporation.

Solar interfacial evaporation is a promising method for solving the global shortage of fresh water. While 2D evaporators can efficiently localize solar-converted heat at the thin layer of the water-air interface, 3D solar evaporators can maximize energy reutilization while maintaining effective mass transport ability, few studies are conducted to explore the effect of gradient porosity on evaporation performance. In this study, a multifield assisted strategy based on a gradient 3D structure with high tortuosity is proposed, which creates a thermal field environment for efficient evaporation through high absorption of sunlight and excellent photothermal conversion and uses the gradient structure to optimize the internal pressure field to enhance water evaporation and transport. This hierarchically nanostructured solar absorber, with porosity inhomogeneity-induced pressure gradient and optimized temperature management, is a valuable design idea for manufacturing a more efficient 3D solar evaporator in the field of seawater desalination. Owing to the understanding of optimizing the dimension by various simulation parameters, the evaporation efficiencies of such structures are found to be 165.7%, suppressing the most evaporator. Moreover, it can provide new ideas and references for the fields of mass transfer and thermal management.

A Metal-Free Direct Decarboxylative Fluoroacylation of Indole Carboxylic Acids with Fluorinated Acids.

A straightforward preparation of diversified fluorinated indol-3-yl ketones was developed by the direct decarboxylative fluoroacylation of indole carboxylic acids. The reaction could be performed on a gram scale under net conditions. Neither a metal catalyst nor an additive was employed. This methodology featured simple reaction conditions, high efficiency, exclusive selectivity, a broad substrate scope, and easy operation, which allowed it to meet the green chemistry requirement of the modern pharmaceutical industry. Control experiments confirmed that a radical process might be involved in the tandem decarboxylative fluoroacylation sequence.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

Prevalence and modifiable risk factors of cognitive frailty in patients with chronic heart failure in China: a cross-sectional study.

BACKGROUND: Cognitive frailty (CF) is currently a significant issue, and most of the associated factors discovered in current studies are not modifiable. Therefore, it is crucial to identify modifiable risk factors that can be targeted for interventions in patients with chronic heart failure (CHF). This study aimed to investigate the prevalence and modifiable risk factors of CF in CHF patients in China. METHODS: In this cross-sectional study, we sequentially enrolled patients diagnosed with CHF. CF served as the dependent variable, assessed through the Montreal Cognitive Assessment (MoCA) Scale and the FRAIL Scale. The independent variable questionnaire encompassed various components, including general demographic information, the Social Support Rating Scale (SSRS), the Simplified Nutrition Appetite Questionnaire (SNAQ), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Logistic regression analysis was employed to identify independent factors contributing to CF. RESULTS: A total of 271 patients with CHF were included in the study. The overall prevalence of CF was found to be 49.4%, with 28.8% of patients exhibiting potentially reversible cognitive frailty and 20.7% showing reversible cognitive frailty. Among middle-young CHF patients, 10.7% had reversible cognitive frailty and 6.4% had potentially reversible cognitive frailty, with a prevalence of CF at 17.1%. Logistic regression analysis revealed that body mass index (OR = 0.826, 95%CI = 0.726-0.938), blood pressure level (OR = 2.323, 95%CI = 1.105-4.882), nutrition status (OR = 0.820, 95%CI = 0.671-0.979), and social support (OR = 0.745, 95%CI = 0.659-0.842) were independent factors associated with CF (p < 0.05). CONCLUSIONS: We observed a relatively high prevalence of CF among Chinese patients diagnosed with CHF. Many factors including BMI, blood pressure level, nutrition status, and social support emerging as modifiable risk factors associated with CF. We propose conducting clinical trials to assess the impact of modifying these risk factors. The outcomes of this study offer valuable insights for healthcare professionals, guiding them in implementing effective measures to improve the CF status in CHF patients during clinical practice.

Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.

BACKGROUND: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified. METHODS: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored. RESULTS: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041). CONCLUSION: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

Characteristics of inhibitory active substances produced by Pseudoalteromonas SW-1.

To confirm the antagonistic activity characterization of the strain Pseudoalteromonas SW-1 (P. SW-1), its cell-free supernatant (CFS) was studied against a clam pathogenic strain of Vibrio Alginolyticu MP-1 (V.MP-1). The CFS of P. SW-1 exhibited evident antagonistic activities against the pathogens, and the absorbance value (600 nm) of V. MP-1 remained at a lower level at 24 h when compared with the control. The results showed that the inhibitory activities of strain P. SW-1 CFS showed differences after treatment with heat, acid and alkali, and proteinase K. The CFS of P. SW-1 inhibitory activities decreased after treatment with heat, but the inhibitory activities of strain P. SW-1 CFS were still effective after treatment with proteinase K for 24 h. The acid and alkali treatments could increase the inhibitory activities of strain P. SW-1 CFS. Therefore, the ammonium sulfate precipitation test also indicated that P. SW-1 could produce some active protein compounds to antagonize pathogenic V. MP-1.

Biomolecular Condensates Decipher Molecular Codes of Cell Fate: From Biophysical Fundamentals to Therapeutic Practices.

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.

[Therapeutic effect and mechanism of Jingfang Granules on acute lung injury based on intestinal flora and fecal metabolomics].

This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury, and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury, mice were randomly divided into a sham group, a model group, and a Jingfang Granules group. After modeling, the mice were continuously administered for 6 days. Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS) metabolomics technology and 16S rRNA high-throughput sequencing technology, changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined, and potential biomarkers were identified. The results showed that Jingfang Granules can regulate 11 biomarkers, including L-glutamic acid, succinic acid, arachidonic acid, linoleic acid, linolenic acid, phenylalanine, sphingosine, 2-hydroxy-2-methyl butyric acid, pyruvate, tryptophan, and palmitic acid. Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst, identifying potential major metabolic pathways. Among them, a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate cycle(TCA cycle), alyoxylate and dicarboxylate metabolism, arginine and proline metabolism, linoleic acid metabolism and linolenic acid metabolism, nitrogen metabolism, D-glutamine and D-gluta-matemetabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism. The results of gut microbiota showed significant differences in bacteria, mainly including Bacteroides, Akkermansia, Lachnospiraceae＿NK4A136＿group, Lachnochlostridium, and Klebsiella. Spearman analysis confirms that Akkermansia and Lachnospiraceae＿NK4A136＿group is a significant positive correlation between the abundance of succinic acid, arachidonic acid, linolenic acid, linoleic acid, butyric acid, and pyruvate in the group; Bacteroides, Klebsiella, Lachnochlostrium are significantly positively correlated with the abundance of L-glutamic acid, phenylalanine, and sphingosine. The above results indicate that the therapeutic effect of Jingfang Granules on acute lung injury is achieved by improving the imbalance of gut microbiota in mice with acute lung injury, balancing the metabolism of alanine, biosynthesis of aminoacyl tRNA, aspartic acid, glutamate, tricarboxylic acid cycle, biosynthesis of phenylalanine, tyrosine, tryptophan, and metabolism of linoleic acid.

Adipose mesenchymal stem cells-derived exosomes alleviate osteoarthritis by transporting microRNA -376c-3p and targeting the WNT-beta-catenin signaling axis.

Osteoarthritis (OA), one of the major diseases afflicting the elderly, is a type of degenerative joint disease related to cartilage and synovium. This study aimed to clarify the role and mechanism of adipose mesenchymal stem cell (ADSC)-derived exosomes (Exos) in OA-induced chondrocyte degradation and synovial hyperplasia, thus improving the quality of life of patients. The rat OA model, chondrocytes, synovial fibroblast models and immunofluorescence were applied to observe the in vivo and in vitro functions of human ADSC (hADSC)-derived Exos in OA and its possible regulatory signaling pathways. Bioinformatics software and luciferase reporter assay were carried out to verify the mechanism of microRNA-376c-3p (miR-376c-3p) in hADSC-derived Exos in OA in vitro. Moreover, Safranine O-Fast Green Cartilage staining, Masson staining, immunohistochemistry and immunofluorescence were conducted to verify the role of miR-376c-3p in hADSC-derived Exos in OA in vivo. hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis both in vivo and in vitro models by repressing the WNT-beta-catenin signaling pathway. For the mechanism exploration in vitro, miR-376c-3p was raised in hADSC-derived Exos and mediated the fibrosis of synovial fibroblasts in OA, and miR-376c-3p targeted the 3'-untranslated region of WNT3 or WNT9a. Meanwhile, the in vivo experiments also corroborated that the miR-376c-3p in hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis. MiR-376c-3p in hADSC-derived Exos repressed the WNT-beta-catenin pathway by targeting WNT3 or WNT9a, and then mitigating OA-induced chondrocyte degradation and synovial fibrosis, thereby providing theoretical basis for clinical implementation of treatment.

Nondestructive and Quantitative Analysis of Cell Wall Regeneration in the Medicinal Macrofungus Ganoderma lingzhi by a Membrane-Fusing Fluorescent Probe.

Ganoderma is a prize medicinal macrofungus with a broad range of pharmaceutical values. To date, various attempts have been made to cultivate Ganoderma to improve the production of secondary metabolites with pharmacological activity. Among the adopted techniques, protoplast preparation and regeneration are indispensable. However, the evaluation of protoplasts and regenerated cell walls usually relies on electron microscopy assays, which require time-consuming and destructive sample preparation and merely provide localized information in the selected area. In contrast, fluorescence assays enable sensitive real-time detection and imaging in vivo. They can also be applied to flow cytometry, providing a collective overview of every cell in a sample. However, for macrofungi such as Ganoderma, the fluorescence analysis of protoplasts and regenerated cell walls is difficult owing to the hindrance of the homologous fluorescent protein expression and the lack of an appropriate fluorescence marker. Herein, a specific plasma membrane probe, TAMRA perfluorocarbon nucleic acid probe (TPFN), is proposed for the nondestructive and quantitative fluorescence analysis of cell wall regeneration. Exploiting the perfluorocarbon membrane-anchoring chains, hydrophilic nucleic acid linker, and fluorescent dye TAMRA, the probe is proven to be selective, soluble, and stable, enabling rapid fluorescence detection of a protoplast sample free of transgenic expression or immune staining. Based on the TPFN and flow cytometry techniques, a quantitative approach is constructed to monitor the process of cell wall growth in a fast, quantitative, and high-throughout manner, and the obtained results are consistent with those of conventional electron microscopy. In principle, with slight modifications or integration, the proposed probe and approach can be adapted to the preparation of cell protoplasts, inspection of cell wall integrity under environmental stress, and programmable membrane engineering for cytobiology and physiology research.

Aptamer-Mediated Enrichment of Rare Circulating Fetal Nucleated Red Blood Cells for Noninvasive Prenatal Diagnosis.

Isolation of circulating fetal nucleated red blood cells (cfNRBCs) from maternal peripheral blood provides a superior strategy for noninvasive prenatal genetic diagnosis. Recent technical advances in single-cell isolation and genetic analyses have promoted the clinical application of circulating fetal cell-based noninvasive prenatal diagnosis. However, the lack of highly specific ligands for rare circulating fetal cell enrichment from massive maternal cells significantly impedes the clinical transformation progress. In this work, aptamers specific to NRBCs were developed through clinical sample-based cell-SELEX. Herein, the complex clinical system provides natural selection stringency through binding competition between target and background cells, and it empowers aptamers with high specificity. An aptamer-based strategy was also established to isolate cfNRBCs from maternal peripheral blood. Results show the remarkable selectivity and affinity of developed aptamers, enabling efficient enrichment of cfNRBCs from abundant maternal cells. Moreover, screening for fetal sex and trisomy syndrome achieved high accuracy through chromosome analysis of enriched cfNRBCs. To the best of our knowledge, this is the first report to develop aptamer ligands for cfNRBC enrichment, providing an efficient strategy to screen cfNRBC-specific ligands and demonstrating broad application potential for cfNRBC-based noninvasive prenatal diagnosis.

Cytopenia: a report of haplo-cord transplantation in twin brothers caused by a novel germline GATA1 mutation and family survey.

Cytopenia due to the abnormal regulation of GATA1 could manifest as varying degrees of thrombocytopenia and/or anemia and more severely in male children than in female children. Here, we describe the case of pancytopenic and transfusion-dependent twin brothers at our center whose bone marrow puncture revealed low bone marrow hyperplasia. Whole-exome sequencing revealed that the twins had a new germline GATA1 mutation (nm_002049: exon 3:c.515 T >C:p.F172S), which confirmed the diagnosis of GATA1 mutation-related pancytopenia. The mutation was inherited from their mother, who was heterozygous for the mutation. Sanger sequencing verified the pathogenicity of the mutation. Further family morbidity survey confirmed that GATA1 mutation-related pancytopenia is an X-linked recessive genetic disorder. We developed haploid hematopoietic stem cell transplantation programs for twins, with the father as the only donor, and finally, the hematopoietic reconstruction was successful. Although they experienced acute graft-versus-host disease, hemorrhagic cystitis, and a viral infection in the early stage, no abnormal manifestations or transplant-related complications were observed 3 months after transplantation. Through hematopoietic stem cell transplantation technology for one donor and two receptors, we eventually cured the twins. The p.F172S variant in the new germline GATA1 mutation may play an essential role in the pathogenesis of GATA1 mutation-related cytopenia.

Application of Carbon Fiber-Reinforced Ceramic Composites in Active Thermal Protection of Advanced Propulsion Systems: A Review.

Thermal protection is one of the crucial issues for the advanced propulsion systems of Reusable Launch Vehicles. New service requirements for materials, such as high strength, low density, low thermal expansion, high thermal stability, etc., are raised for the thermal structure with the increasing demand of flight Mach numbers and thrust-to-weight ratio. Carbon fiber-reinforced ceramic composites, which generally meet the aforementioned requirements, show great potential for various applications and they have been widely applied in the thermal protection for hypersonic vehicles. This paper gives a comprehensive and systematic review of current research status for carbon fiber-reinforced ceramic composites applied in the thermal structure of advanced propulsion systems. Three aspects are presented and discussed: the ceramic composites fabrication and the property characterization, the thermal performance of composite thermal structure used in practical engines, and the numerical methods for predicting mechanical and thermal properties of composites as well as the physicochemical phenomenon in the cooling channels. Firstly, the main manufacturing processes for the carbon-reinforced ceramic composites are presented and the corresponding advantages and disadvantages are analyzed. The high-temperature oxidation and ablation behaviors of composites are demonstrated and the improvement of oxidation and ablation resistance by introducing the ultra-high-temperature ceramics into C/C composites is discussed in detail. Then, several typical applications of carbon fiber-reinforced ceramic composites (mainly C/SiC), including the work of RCI, JAXA and NASA, have been reviewed and analyzed. After that, the current research status of macroscale equivalent and multiscale numerical methods for predicting the mechanical and thermal properties of composites as well as the complex physicochemical phenomenon occurring in hydrocarbon fuels are sorted out. Finally, several potential prospects are pointed out for the future research on the thermal protection of advanced propulsion systems based on the carbon fiber-reinforced ceramic composites.

Organocatalytic Aza-Michael/Mannich Cascade Reaction: Synthesis of Enantioenriched 3,3'-Spirooxindole γ-Lactams.

Highly enantioselective synthesis of 3,3'-spirooxindole γ-lactams with three contiguous stereocenters (two quaternary) was achieved. The aza-Michael/Mannich cascade reaction of α-imine-ß-oxobutanamides and methyleneindolinones catalyzed by a bifunctional diaminocyclohexane-derived thiourea catalyst gave the desired products in moderate to good yields (up to 78%), moderate to good diastereoselectivities (up to 10:1 dr), and good to excellent enantioselectivities (up to >99% ee). A gram-scale synthesis and some transformations of 3,3'-spirooxindole γ-lactams were also carried out.

COAP-Pd Catalyzed Asymmetric Allylic Alkylation of Azlactones with MBH Carbonates: Access to Unnatural α-Quaternary Stereogenic Glutamic Acid Derivatives.

A palladium-catalyzed regioselective and asymmetric allylic alkylation of azlactones with MBH carbonates has been developed with chiral oxalamide-phosphine ligands. The corresponding reaction afforded a range of optically active γ-arylidenyl glutamic acid derivatives bearing an α-chiral quaternary stereocenter in good yields with excellent linear regio- and high enantioselectivity. This protocol furnishes an alternative approach for the construction of enantio-enriched unnatural α-amino acid derivatives.

Application of food exchange portion method in home-based nutritional intervention for elderly patients with chronic heart failure.

BACKGROUND: The home treatment of elderly patients with chronic heart failure (CHF) is often accompanied by malnutrition, which increases the risk of re-hospitalisation and affects the prognosis. Therefore, how to effectively improve the nutritional self-management of patients is a current focus of medical research. This study aims to test the effect of home-based nutritional intervention method on improving the nutritional status of elderly patients with CHF. METHODS: A total of 90 hospitalised elderly patients with CHF were randomly divided into the experimental group (n = 45) and the control group (n = 45). The patients in both groups were given standardised drug therapy and their nutritional status was evaluated using a body composition analyser prior to discharge (protein, body fat percentage, visceral fat area, skeletal muscle, upper arm muscle circumference, left lower limb and right lower limb muscle mass), with the cardiopulmonary function evaluated using a six-minute walk test and the metabolic equivalents method. The control group was given general nutrition education and routine dietary guidance from cardiac rehabilitation nurses, while the experimental group was given an individualised nutrition prescription by dietitians based on the evaluation results, according to which one-to-one food exchange dietary intervention training was given until the patients mastered the process. RESULTS: The nutritional indexes at the end of the study were significantly higher in the experimental group than in the control group and were higher than those before the intervention (P < 0.05). The muscle circumference of the upper arm, the muscle mass of the left lower limb and the right lower limb had no statistical significance following the intervention compared to the control group and before the intervention (P > 0.05). The cardiopulmonary function indexes were significantly better in the experimental group at the end of the study than before the intervention and were better than those in the control group, with statistically significant differences (P < 0.05), while no significant changes were observed in the control group before and after the intervention (P > 0.05). CONCLUSION: The home-based nutritional intervention method of food exchange portions can effectively improve the nutritional status of elderly patients with CHF, with the distribution of visceral fat more reasonable and the cardiopulmonary function and exercise endurance improved.