Association between nutritional risk and fatigue in frailty conditions for older adult patients: a multicentre cross-sectional survey study.

BACKGROUND AND AIMS: Frailty is widespread in the elderly, while there is a bi-directional relationship between frailty and malnutrition. The objectives of this study were to investigate the prevalence and correlation of frailty and nutritional risk in older adult patients and to analyse the factors associated with fatigue which is one indicator of frailty. METHODS: This cross-sectional multicentre survey study was conducted in five hospitals in the same city from 01 January 2021 to 01 December 2021. We collected information on gender, age, diseases, medication and dietary status. Frailty status was diagnosed using the FRAIL scale, and Nutritional Risk Screening-2002 was used to screen the nutritional risk. Spearman rank correlation was used to analyse the correlation between frailty and nutritional risk. Univariate and multivariate logistic regression analyses were used to analyse the risk factors related to fatigue in all patients and inpatients. RESULTS: Among 2016 older adult patients, the prevalence of frailty was 15.1% (305/2016), the prevalence of nutritional risk was 16.2% (327/2016) and the overlap prevalence of frailty and nutritional risk was 7.3% (147/2016). Multivariate analysis showed that nutritional risk (OR 3.109, 95% CI 2.384 to 4.056, p<0.001) was an independent risk factor for fatigue in all patients; similar results were found for nutritional risk (OR 2.717, 95% CI 2.068 to 3.571, p<0.001) in hospitalised patients. CONCLUSIONS: Frailty and nutritional risk are prevalent among older adult patients, and nutritional risk is associated with the occurrence of fatigue in older adult patients and older adult inpatients. TRIAL REGISTRATION NUMBER: China Clinical Trial Registry (Registered No. ChiCTR-EPC-14005253).

Bone-organ axes: bidirectional crosstalk.

In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines (also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles (EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.

Modeling Analysis of Complex Deformation of Woven Coating Film during the Cyclic Tensile Process.

It is difficult for the existing Burgers model to accurately depict the off-axis cyclic drawing process of woven coatings. In this paper, the mechanical deformation of woven PVC (polyvinyl chloride)-coated film at different temperatures is investigated. One-dimensional (1D) and two-dimensional (2D) constitutive models were established to characterize cyclic deformation processes. The 1D model is an improved Burgers model. The effects of the time dependence of the viscosity coefficient and the ratio of elastic to viscous deformation are considered simultaneously. The accuracy of the 1D model for predicting the cyclic nonlinear deformation at different temperatures and loading rates is improved. The 2D model is a nonlinear orthotropic model using polynomials. On the basis of the single-objective genetic algorithm, the inverse algorithm is used to obtain the shear polynomial coefficients in the tension phase and the shear modulus in the unloading phase, which circumvents performing the difficult shear test. UMAT subroutines of off-axis stretching and off-axis cyclic stretching are written separately. The intelligent inverse algorithm program consists of a single-objective genetic algorithm program, a finite element parametric modelling program, and a UMAT subroutine. The simulation results are compared with the off-axis cyclic tensile test data to validate the effectiveness and accuracy of the proposed 2D model for the analysis of the woven PVC-coated films in the tension-shear coupling state.

On Impact Damage and Repair of Composite Honeycomb Sandwich Structures.

This study is conducted on glass fiber-reinforced composite honeycomb sandwich structures by introducing delamination damage through low-velocity impact tests, establishing a three-dimensional progressive damage analysis model, and evaluating the delamination damage characteristics and laws of honeycomb sandwich structures under different impact energies through experiments. Repair techniques and process parameters for delamination damage are explored. It is found that as the impact energy increases, the damage area of honeycomb sandwich panels also increases, and the delamination damage extends from the impact center to the surrounding areas, accompanied by damage such as fiber fracture and matrix cracking. The strength recovery rates of sandwich panels at impact energies of 5 J, 15 J, and 25 J after repair are 71.90%, 65.89%, and 67.10%, respectively, which has a considerable repair effect. In addition, a progressive damage model for low-velocity impact on the composite honeycomb sandwich structure is established, and its accuracy and reliability are verified.

The role and mechanisms of microvascular damage in the ischemic myocardium.

Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.

Design and Analysis of a New Multi-Part Composite Frangible Cover.

In this paper, a new multi-part composite frangible cover (MCFC) was designed and fabricated. The frangible cover, manufactured with a traditional manual lay-up method, is designed to conduct a simulated missile launch test using a specially developed test device. A weak zone structure of the composite multi-part frangible cover was designed, and the separation process of the cover was studied by numerical simulation. Based on the strength envelope of the weak zone and the equal-strength design principle, a design method for the weak zone structure of the composite multi-part frangible cover was proposed. A finite element model of the composite multi-part frangible cover was established, and the separation process was numerically simulated and analyzed. Afterward, the verification experiments were carried out. Close agreements between the numerical and experimental results are observed.

Synthesis and Cytotoxicity Assessment against Human Colorectal Cancer Cell Lines of Quaternary 8-Dichloromethyl Protoberberine Alkaloids.

Twenty-two quaternary 8-dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol/water partition coefficients by up to values 3-4 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds in vitro. The IC50 values of antiproliferative activity of quaternary 8-dichloromethyl-pseudoberberine 4-chlorobenzenesulfonate and quaternary 8-dichloromethyl-pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31 µM and 0.41 µM, respectively, significantly stronger than those of other compounds and positive control 5-fluorouracil. These findings suggest that 8-dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs.

Chemoproteomics Reveals That Quaternary Protoberberine Alkaloids Inhibit Telomerase Activity Oncologically by Binding to PES1.

Natural QPAs have anti-cancer property. The prodrugs of QPAs synthesized in our work with significantly improved solubility showed significantly stronger activity in animal experiments. Nevertheless, the mechanism of action of QPAs for treating cancers remains poorly understood. Here, a chemoproteomic study reveals that QPAs non-covalently and multivalently bind to PES1 in CRC cells, which impinges on the direct interaction between hTERT and hTR in the assembly of the telomerase complex, downregulates telomerase activity, and so promotes the aging process of CRC cells. This study is beneficial for us to conduct extensively the pharmaceutical chemistry research of QPAs.

Hippocampus shape characterization with 3D Zernike transformation in clinical Alzheimer's disease progression.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia among older adults. Mild cognitive impairment (MCI) is considered a transitional phase between healthy cognitive aging and dementia. Progressive brain volume reduction/atrophy, particularly of the hippocampus, is associated with the transition from normal to MCI, and then to AD. We aimed to develop methods to characterize the shape of hippocampus and explore its potential as an imaging marker to monitor clinical AD progression. We implemented a 3D Zernike transformation to characterize the shape changes of hippocampus in 428 older subjects with high-quality T1 -weighted volumetric brain scans from the Alzheimer's Disease Neuroimaging Initiative data set (151 normal, 258 MCI, and 19 AD). Over 2 years, 15 cognitively normal subjects converted to MCI, and 42 subjects with MCI converted to AD. We found a significant correlation between hippocampal volume changes and Zernike shape metrics. Before a clinical diagnosis of AD, the shapes of the left and right hippocampi changed slowly. After AD diagnosis, both volume and shape changed rapidly but were uncorrelated to each other. During the transition from a clinical diagnosis of MCI to AD, the shape of the left and right hippocampi changed in a correlated manner but became uncorrelated after AD diagnosis. Finally, the pace of hippocampus shape change was associated with its shape and the subject's age and disease condition. In conclusion, the hippocampus shape features characterized with 3D Zernike transformation, in complement to volume measures, may serve as a novel imaging marker to monitor clinical AD progression.

Effect of Interlaminar Toughness on the Residual Compressive Capacity of Carbon Fiber Laminates with Different Types of Delamination.

In this paper, the effect of interlaminar properties and the type of delamination defects on the residual compression properties of carbon fiber laminates were experimentally investigated. A new method, which employed magnetic force to guide the arrangement direction of stainless steel particles between layers of laminates, was adopted to improve the interlayer toughness. The digital image correlation, C-scan, and micro-CT were used to measure and identify the compression failure damages. Test results showed that the compressive strength of the intact carbon fiber laminates was 299.37 MPa, and the one of specimens containing the deeply buried delamination, the through-width delamination, and the surface delamination decreased by 55.98 MPa, 58.69 MPa, and 60.23 MPa, respectively. The compressive strength of the specimens containing the deeply buried delamination only decreased by 14.01 MPa when the mode I toughness increased by 81.88%, and the specimen containing the surface delamination only decreased by 30.86 MPa when the mode II fracture toughness increased by 87.72%. However, improving the fracture toughness could not strengthen the specimens containing the through-width delamination. Moreover, a qualitative dynamic damage relationship, which described the relationship between delamination expansion and compression damage vividly, was proposed. The reason the increase of the toughness could improve the residual compression performance of the laminates containing delamination was that the higher fracture toughness hindered the secondary expansion of the delamination during the compression process so that the delamination area could almost remain unchanged.

Trifluoromethylation of dihydrocoptisines and the effect on structural stability and XBP1-activating activity.

In order to obtain new dihydrocoptisine-type compounds with stable structure and activating XBP1 transcriptional activity, (±)-8-trifluoromethyldihydrocoptisine derivatives as target compounds were synthesized from quaternary ammonium chlorides of coptisine alkaloids as starting materials by a one-step reaction. The structures of the synthesized compounds were confirmed by 1H-, 13C-, and 19F-NMR as well as HRESIMS methods. These compounds showed more significant structural stability and activating XBP1 transcription activity in vitro than dihydrocoptisine as positive control. No obvious cytotoxicity on normal cell in vitro was observed with (±)-8-trifluoromethyldihydrocoptisines. Trifluoromethylation can be used as one of the fluorine modification strategies for dihydrocoptisines to guide follow-up studies on structural modification of coptisine-type alkaloids and on anti-Ulcerative colitis drugs with coptisines.

A unified total synthesis of benzo[d][1,3]dioxole-type benzylisoquinoline alkaloids of aporphines, coptisines, and dibenzopyrrocolines.

The first total synthesis of (S)-(+)-ovigerine, (S)-(+)-N-formylovigerine, and (6aS,6a'S)-(+)-ovigeridimerine of aporphine alkaloids with a benzo[d][1,3]dioxole structure feature was established. The strategy was based upon the well-known Pd-catalyzed arylation to set the aporphine framework, and Noyori asymmetric hydrogenation followed by diastereoselective resolution to achieve excellent enantioselectivity. By slightly modifying the total synthetic route and strategically combining it with a aza-Michael addition, Bischler-Napieralski reaction and N-arylation, this methodology was also applied to the total syntheses of benzo[d][1,3]dioxole-type benzylisoquinoline alkaloids of coptisines and dibenzopyrrocolines, including two impatiens, tetrahydrocoptisine, and quaternary coptisine bromide of coptisines and two dibenzopyrrocoline analogues, with the syntheses of all of these target compounds being efficient. Among the nine synthesized compounds, the total syntheses of the three aporphines and the two impatiens, all with ee values of greater than 99%, were reported for the first time. This work also represents the first unification of synthetic routes for the total synthesis of benzo[d][1,3]dioxole-type aporphines, coptisines, and dibenzopyrrocolines.

Improved Shear Strength Performance of Compacted Rubberized Clays Treated with Sodium Alginate Biopolymer.

This study examines the potential use of sodium alginate (SA) biopolymer as an environmentally sustainable agent for the stabilization of rubberized soil blends prepared using a high plasticity clay soil and tire-derived ground rubber (GR). The experimental program consisted of uniaxial compression and scanning electron microscopy (SEM) tests; the former was performed on three soil-GR blends (with GR-to-soil mass ratios of 0%, 5% and 10%) compacted (and cured for 1, 4, 7 and 14 d) employing distilled water and three SA solutions-prepared at SA-to-water (mass-to-volume) dosage ratios of 5, 10 and 15 g/L-as the compaction liquid. For any given GR content, the greater the SA dosage and/or the longer the curing duration, the higher the uniaxial compressive strength (UCS), with only minor added benefits beyond seven days of curing. This behaviour was attributed to the formation and propagation of so-called "cationic bridges" (developed as a result of a "Ca2+/Mg2+ ⟷ Na+ cation exchange/substitution" process among the clay and SA components) between adjacent clay surfaces over time, inducing flocculation of the clay particles. This clay amending mechanism was further verified by means of representative SEM images. Finally, the addition of (and content increase in) GR-which translates to partially replacing the soil clay content with GR particles and hence reducing the number of available attraction sites for the SA molecules to form additional cationic bridges-was found to moderately offset the efficiency of SA treatment.

Expression of G9a in Auditory Cortex Is Downregulated in a Rat Model of Age-Related Hearing Loss.

G9a is essential for dendritic plasticity and is associated with neurological disorders. The possible relationship between age-related hearing loss and G9a expression in the auditory cortex has not been fully explored. This study aimed to understand the expression patterns of G9a-mediated histone methylations in the auditory cortex during aging. Using immunofluorescence and western blotting, we demonstrated that a significant reduction in G9a expression observed in the auditory cortex of 24-month-old rats compared to 3-month-old rats, was associated with remarkable hearing threshold elevation and hair cell loss. Correspondingly, histone H3 lysine 9 (H3K9) mono- and dimethylation (marked by H3K9me1 and H3K9me2, respectively), which were regulated by G9a activity, also evidently decreased during aging. These findings, which merit further investigation, suggest a possible association between G9a-mediated histone methylations and central age-related hearing disorders.

Dynamic gene regulatory network reconstruction and analysis based on clinical transcriptomic data of colorectal cancer.

Inferring dynamic regulatory networks that rewire at different stages is a reasonable way to understand the mechanisms underlying cancer development. In this study, we reconstruct the stage-specific gene regulatory networks (GRNs) for colorectal cancer to understand dynamic changes of gene regulations along different disease stages. We combined multiple sets of clinical transcriptomic data of colorectal cancer patients and employed a supervised approach to select initial gene set for network construction. We then developed a dynamical system-based optimization method to infer dynamic GRNs by incorporating mutual information-based network sparsification and a dynamic cascade technique into an ordinary differential equations model. Dynamic GRNs at four different stages of colorectal cancer were reconstructed and analyzed. Several important genes were revealed based on the rewiring of the reconstructed GRNs. Our study demonstrated that reconstructing dynamic GRNs based on clinical transcriptomic profiling allows us to detect the dynamic trend of gene regulation as well as reveal critical genes for cancer development which may be important candidates of master regulators for further experimental test.

Syntheses and Structure-Activity Relationships in Antibacterial Activity against Clostridium difficile and XBP1 Activation Property of 13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines.

13-[(N-Alkylamino)methyl]-8-oxodihydrocoptisines were synthesized to evaluate antibacterial activity against Clostridium difficile and activating x-box-binding protein 1 (XBP1) activity, biological properties both associated with ulcerative colitis. Improving structural stability and ameliorating biological activity were major concerns. Different substituents on the structural modification site were involved to explore the influence of diverse structures on the bioactivities. The target compounds exhibited the desired activities with definite structure-activity relationship. In the series of 13-[(N-n-alkylamino)methyl]-8-oxodihydrocoptisines, the length of n-alkyl groups has a definite effect on the bioactivity, elongation of the length increasing the antibacterial activity. The synthesized compounds were determined to display strong or weak XBP1-activating activity in vitro. The preliminary results of this study warrant further medicinal chemistry studies on these synthesized compounds.

Syntheses and Structure-Activity Relationships in Growth Inhibition Activity against Human Cancer Cell Lines of 12 Substituted Berberine Derivatives.

In this study, quaternary berberine chloride is used as a lead compound to design and synthesize a series of berberine-12-amine derivatives to evaluate the growth inhibition activity against human cancer cell lines. Forty-two compounds of several series were obtained. The quaternary berberine-12-N,N-di-n-alkylamine chlorides showed the targeted activities with the IC50 values of most active compounds being dozens of times those of the positive control. A significant structure-activity relationship (SAR) was observed. The activities of quaternary berberine-12-N,N-di-n-alkylamine chlorides are significantly stronger than those of the reduced counterparts. In the range of about 6-8 carbon atoms, the activities increase with the elongation of n-alkyl carbon chain of 12-N,N-di-n-alkylamino, and when the carbon atom numbers are more than 6-8, the activities decrease with the elongation of n-alkyl carbon chain. The activities of the tertiary amine structure are significantly higher than that of the secondary amine structure.

Increased CD200 levels in peripheral blood mononuclear cells of patients with primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with an unknown etiology. CD200 is associated with many autoimmune diseases, but little is known about its role in pSS. This study aims to correlate the expression of CD200 with pSS and evaluate its significance. METHODS: Plasma CD200, CD200R, and interleukin (IL)-17 levels were measured and analyzed by enzyme-linked immunosorbent assay. Messenger RNA levels of CD200 and CD200R in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). Following pretreatment of CD200-Fc, the protein levels of IL-17A were measured in PBMCs from patients and healthy controls. RESULTS: Results showed that, compared to CD200 in healthy controls, the relative levels in PBMCs from pSS were greater than 2-fold. In addition, CD200 levels in plasma positively correlated with IL-17 levels, as well as between plasma CD200 and pSS activity indexes (including immunoglobulin G and European League Against Rheumatism SS Disease Activity Index). While CD200R levels were significantly decreased in pSS patients, no correlation could be found. Furthermore, the protein level of IL-17 decreased after pretreatment of CD200-Fc in PBMCs from pSS patients. CONCLUSION: Our results suggested that the CD200/CD200R pathway is involved in pSS pathogenesis. It is hypothesized that regulation of IL-17 expression affects Th17 differentiation. This newly discovered pathway could give rise to a novel targeted therapy for pSS.

Joining Illumina paired-end reads for classifying phylogenetic marker sequences.

BACKGROUND: Illumina sequencing of a marker gene is popular in metagenomic studies. However, Illumina paired-end (PE) reads sometimes cannot be merged into single reads for subsequent analysis. When mergeable PE reads are limited, one can simply use only first reads for taxonomy annotation, but that wastes information in the second reads. Presumably, including second reads should improve taxonomy annotation. However, a rigorous investigation of how best to do this and how much can be gained has not been reported. RESULTS: We evaluated two methods of joining as opposed to merging PE reads into single reads for taxonomy annotation using simulated data with sequencing errors. Our rigorous evaluation involved several top classifiers (RDP classifier, SINTAX, and two alignment-based methods) and realistic benchmark datasets. For most classifiers, read joining ameliorated the impact of sequencing errors and improved the accuracy of taxonomy predictions. For alignment-based top-hit classifiers, rearranging the reference sequences is recommended to avoid improper alignments of joined reads. For word-counting classifiers, joined reads could be compared to the original reference for classification. We also applied read joining to our own real MiSeq PE data of nasal microbiota of asthmatic children. Before joining, trimming low quality bases was necessary for optimizing taxonomy annotation and sequence clustering. We then showed that read joining increased the amount of effective data for taxonomy annotation. Using these joined trimmed reads, we were able to identify two promising bacterial genera that might be associated with asthma exacerbation. CONCLUSIONS: When mergeable PE reads are limited, joining them into single reads for taxonomy annotation is always recommended. Reference sequences may need to be rearranged accordingly depending on the classifier. Read joining also relaxes the constraint on primer selection, and thus may unleash the full capacity of Illumina PE data for taxonomy annotation. Our work provides guidance for fully utilizing PE data of a marker gene when mergeable reads are limited.

Racemic 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-ones from Juglans regia flowers.

Three previously undescribed (±)-3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives were isolated from Juglans regia flowers. Elucidation of the 2D structures of these first-reported compounds was completed via regular spectroscopic methods. The assignment of racemic nature of these compounds was achieved using the examination of their chiral HPLC profiles. (±)-2,3-Dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one, (±)-2,3-dihydro-4',5,8,8'-tetrahydroxy-(1,1'-binaphthalen)-4(1H)-one, and (±)-2,3-dihydro-1',5,5',8-tetrahydroxy-(1,2'-binaphthalen)-4(1H)-one were the structures of these racemic compounds, all taking on central chirality. The resolution of all the racemic compounds was conducted and achieved using a chiral HPLC procedure. The absolute configurations of the three isolated pairs of enantiomers were assigned via time-dependent density functional theory calculations from the electronic circular dichroism data. The findings in this paper demonstrated that the relevant biochemical reactions for the construction of these 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives in the test plant are nonselective. The (±)-2,3-dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one showed selective inhibitory activity on tumor cells growth, preliminarily supporting the application of Juglans regia flowers to protect against cancers in a few Chinese folk areas.