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Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair. We used mineral-coated microparticles to deliver TGF-β1 mRNA to autologous BMAC. mRNA-activated BMAC was suspended in peripheral blood to generate therapeutic BMAC clots, which were then implanted in rabbit osteochondral defects. Tracking studies revealed that the clots were reliably maintained in the defects for at least 2 weeks. TGF-β1 mRNA delivery significantly increased TGF-β1 production in BMAC clots and increased early expression of articular chondrocyte markers within osteochondral defects. At 9 weeks post-surgery, the mRNA-treated defects had a superior macroscopic cartilage appearance, decreased type I collagen deposition, increased stain intensity for type II collagen and increased glycosaminoglycan deposition area when compared to the controls. Despite the transient expression of therapeutic mRNA we have detected lasting effects, such as a decrease in fibrocartilage formation demonstrated by the decrease in type I collagen deposition and the improvement in macroscopic appearance in the treatment group.

Abstract Background Oral health literacy (OHL) might have an impact on oral health outcomes. Currently, relatively few related studies have been conducted among older people. The aim of this study was to explore the impacts of OHL on oral health outcomes in older adults in a cross-sectional design. Methods From November to December 2023, through the utilization of the cluster sampling approach, a questionnaire survey was carried out among elderly patients visiting the Prosthodontics Department of West China hospital of Stomatology. Data were collected through the general information questionnaire, the Chinese version of the Oral Health Literacy Scale, the Geriatric Oral Health Assessment Index, and oral examinations. Descriptive statistics, binary logistic regression, and poisson regression were used to analyse the data. Results A total of 407 valid questionnaires were recovered, with an effective retrieval rate of 98.79%. After adjustment for sociodemographic, economic and oral health behaviours, the results of the binary logistic regression indicated that the correlations between OHL and self-rated oral health were not statistically significant, while OHL was a predictor variable for dental expenditures within the past year (OR = 0.591; 95%CI: 0.371–0.939), and the poisson regression revealed that OHL was a predictor variable of the quality of life (PR = 1.062, 95%CI: 1.030–1.084) and the number of lost teeth (PR = 0.917, 95%CI: 0.865–0.972). Conclusions This study showed that OHL was closely associated with recent dental expenditure, oral health-related quality of life and the number of lost teeth. These findings could contribute to the planning and development of oral health education programs aimed at enhancing the OHL among the elderly population.

Abstract Background With the advance of next-generation sequencing, various gene-based rare variant association tests have been developed, particularly for binary and continuous phenotypes. In contrast, fewer methods are available for traits not following binomial or normal distributions. To address this, we previously proposed a set of burden- and kernel-based rare variant tests for count data following zero-inflated Poisson (ZIP) distributions, referred to as ZIP-b and ZIP-k tests. We sought to extend the methods to accommodate negative binomial distribution and implemented these tests in a new R package. Results We introduce ZIM4rv, an R package designed to analyze the association of rare variants with zero-inflated counts outcomes. Our package offers two novel models developed by our team: our previously proposed ZIP-b and ZIP-k tests, and the newly derived Negative Binomial Burden and Kernel Test (ZINB-b, ZINB-k). Additionally, we include an ad-hoc two-stage analysis, testing zero and non-zero as a binary outcome and non-zero as a continuous outcome, respectively. To showcase the utility of our platform, we applied this program to analyze neuritic plaque count data from the ROSMAP cohort. Conclusion The R package ZIM4rv presents an integrated workflow for conducting association tests on a set of rare variants with zero-inflated counts data.

Abstract Prime editing enables precise and efficient genome editing, but its efficacy is hindered by pegRNA’s 3’ extension, forming secondary structures due to high complementarity with the protospacer. The continuous presence of the prime editing system also leads to unintended indel formation, raising safety concerns for therapeutic applications. To address these challenges, we develop a mismatched pegRNA (mpegRNA) strategy that introduces mismatched bases into the pegRNA protospacer, reducing complementarity and secondary structure formation, and preventing sustained activity. Our findings show that mpegRNA enhances editing efficiency by up to 2.3 times and reduces indel levels by 76.5% without compromising performance. Combining mpegRNA with epegRNA further increases efficiency up to 14-fold, or 2.4-fold in PE4max/PE5max systems, underscoring its potential in research and therapy. AlphaFold 3 analysis suggests that the optimal mpegRNA structure contributes significantly to improved editing outcomes. Overall, mpegRNA advances prime editing technology, improving efficiency while reducing indels.

The widespread use of cellulose nanofiber (CNF)-based aerogels is hindered by their limited flame retardancy and mechanical properties. This study addresses these challenges by developing cellulose nanofiber/sodium alginate/fly ash (CNF/SA/FA) aerogel through a one-pot method, utilizing industrial waste fly ash (FA) as a reinforcing material. Various characterization and analytical techniques were employed to evaluate the properties of the CNF/SA/FA aerogel. The findings have revealed that resulting aerogel exhibited excellent thermal insulation performance, with a thermal conductivity of 0.485 W/(m·K), along with an impressive compressive strength of 88.4 kPa and favorable shape processability. Vertical combustion tests demonstrated a V-0 rating, indicating superior flame retardancy, and the aerogel achieved a remarkable 79.16% residual carbon, confirming their effective heat shielding capabilities. Notably, the incorporation of FA significantly enhanced both the thermal and mechanical properties of the composite aerogel, presenting a sustainable and effective solution to optimizing the properties of aerogel for thermal insulation.

Infantile reversible cytochrome c oxidase (COX) deficiency myopathy is a mitochondrial rare disease with onset age of first day to three months with symptoms of generalized muscle weakness and severe hypotonia. Despite its initial serious conditions, the symptoms may improve spontaneously later in their life, with the so-called “benign” myopathy accordingly. This benign mitochondrial myopathy might be improved in their later life, which is different from most mitochondrial myopathies with progression by age. Therefore, we depicted the rare case of her clinical course during our medical practice, anticipating to provide more information of this rare disease.

BackgroundWe intended to observe the effects of different doses of remimazolam besylate via intravenous induction on the quality of sedation and cardiac function in elderly patients.MethodsA total of 135 ASA I–III patients undergoing elective laparoscopic cholecystectomy were selected. They were divided into three groups and they were randomized. Low dose group (Group L): Remimazolam besylate 0.2 mg/kg; middle dose group (Group M): Remimazolam besylate 0.3 mg/kg; High dose group (Group H): Remimazolam besylate 0.4 mg/kg. There were 45 patients in each group. The blood pressure, heart rate, BIS values, cardiac function before induction (T0), after induction (T1) and after intubation (T2), as well as the length of loss of consciousness, duration of sedation, and extubation and adverse events were recorded.ResultsAt T1 and T2, systolic and diastolic blood pressure in Group M were lower than those in Group L, but higher than those in Group H, with statistically significant differences (P 0.05) in BIS values between Group M and Group H; At T1 and T2, the cardiac output and stroke volume in Group M were higher than those in Group H, while the systemic vascular resistance in Group M was lower than that in Group H, with statistically significant differences (P

In flowering plants, MADS-box genes play regulatory roles in flower induction, floral initiation, and floral morphogenesis. Isatis indigotica (I. indigotica) is a traditional Chinese medicinal plant. However, available information concerning MADS-box genes in I. indigotica is insufficient. Based on the sequencing data of the I. indigotica transcriptome, we identified MADS-box gene-encoding transcription factors that have been shown to play critical roles in developmental processes. In this study, 102 I. indigotica MADS-box genes were identified and categorized into type I (Mα, Mβ, and Mγ) and type II (MIKCC and MIKC*) subfamilies. IiMADS proteins in the same cluster had similar motifs and gene structures. In total, 102 IiMADS-box genes were unevenly distributed across seven chromosomes. APETALA1 (AP1) encodes a MADS-box transcription factor which plays a pivotal role in determining floral meristem identity and also modulates developmental processes within the perianth. We then selected IiAP1 for functional studies and found that it is localized to the nucleus and highly expressed in inflorescence, sepals, and petals. The ectopic expression of IiAP1 in Arabidopsis resulted in early flowering and abnormal development of floral organs. Taken together, this research study carried out a systematic identification of MADS-box genes in I. indigotica and demonstrated that IiAP1 takes part in the regulation of floral transition and formation.

Understanding topological defects-controlled structural degradation of layered oxides--a key cathode material for high-performance lithium-ion batteries--plays a critical role in developing next-generation cathode materials. Here, by constructing a nanobattery in an electron microscope enabling atomic-scale monitoring of electrochemcial reactions, we captured the electrochemically driven atomistic dynamics and evolution of dislocations--a most important topological defect in material. We deciphered how dislocations nucleate, move, and annihilate within layered cathodes at the atomic scale. Specifically, we found two types of dislocation configurations, i.e., single dislocations and dislocation dipoles. Both pure dislocation glide/climb and mixed motions were captured, and the dislocation glide and climb velocities were first experimentally measured. Moreover, dislocation activity-mediated structural degradation such as crack nucleation, phase transformation, and lattice reorientation was unraveled. Our work provides deep insights into the atomistic dynamics of electrochemically driven dislocation activities in layered oxides. [ABSTRACT FROM AUTHOR]