Anticipation and Verification of Dendrobium-Derived Nanovesicles for Skin Wound Healing Targets, Predicated Upon Immune Infiltration and Senescence.

Background: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium. Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1ß and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1ß expression, enhancing wound healing. Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1ß overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1ß expression, accelerating skin wound tissue repair.

Differential Associations of APOEɛ2 and APOEɛ4 Genotypes with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Individuals Without Dementia.

BACKGROUND: The APOE genotype has emerged as the major genetic factor for AD but differs among different alleles. OBJECTIVE: To investigate the discrepant effects of APOE genotype on AD cerebrospinal fluid (CSF) biomarkers. METHODS: A total of 989 non-demented ADNI participants were included. The associations of APOEɛ2 and APOEɛ4 with CSF biomarkers were investigated using linear regression models. Interaction and subgroup analyses were used to investigate the effects of sex and age on these associations. Furthermore, we used mediation analyses to assess whether Aß mediated the associations between APOE genotypes and tau. RESULTS: APOEɛ2 carriers only showed higher Aß levels (ß [95% CI] = 0.07 [0.01, 0.13], p = 0.026). Conversely, APOEɛ4 carriers exhibited lower Aß concentration (ß [95% CI] = -0.27 [-0.31, -0.24], p < 0.001), higher t-Tau (ß [95% CI] = 0.25 [0.08, 0.18], p < 0.001) and higher p-Tau (ß [95% CI] = 0.31 [0.25, 0.37], p < 0.001). Subgroup analysis showed that APOE ɛ2 was significantly positively associated with Aß only in females (ß [95% CI] = 0.12 [0.04, 0.21], p = 0.005) and older people (ß [95% CI] = 0.06 [0.001, 0.12], p = 0.048). But the effects of APOE ɛ4 were independent of gender and age. Besides, the associations of APOE ɛ4 with t-Tau and p-Tau were both mediated by baseline Aß. CONCLUSIONS: Our data suggested that APOEɛ2 could promote Aß clearance, while the process could be modified by sex and age. However, APOEɛ4 might cause the accumulation of Aß and tau pathology independent of sex and age.

A single transition metal atom anchored on Nb2C as an electrocatalyst for the nitrogen reduction reaction.

Nitrogen (N2) reduction to produce ammonia (NH3) under milder conditions is attractive as NH3 has been widely used in various fields. The electrocatalytic nitrogen reduction reaction (NRR) is considered to be a more moderate and green method for ammonia synthesis. Herein, using density functional theory (DFT) computations, we investigated the potential application of single-atom catalysts (SACs) toward the NRR, in which transition metal (TM, TM = Ti, V, Mn, Fe, Co, Y, Zr, Mo) atoms are supported on Nb2C (TM-Nb2C). Through our screening, Fe-Nb2C is highlighted from 8 candidate systems as the superior SAC for the NRR with a low limiting potential of -0.47 V. Meanwhile, a volcano plot between UL (NRR) and the ICOHP values of the N-H bond in *NH2 is established to determine the optimal ICOHP values that can be used as a simple descriptor of the NRR performance of Fe-Nb2C.

Defective Mo2C as a promising electrocatalyst for the nitrogen reduction reaction.

The electrocatalytic nitrogen reduction reaction under ambient conditions is considered as a promising alternative to the Haber-Bosch process for NH3 production. However, developing low-cost and high-efficiency electrocatalysts for N2 reduction remains a challenge. Herein, we propose VC-Mo2C with C vacancies as a novel nitrogen reduction reaction (NRR) electrocatalyst based on density functional theory (DFT) calculations. The computational results show that N2 in the gas phase can be fully activated on the surface of VC-Mo2C and can be efficiently reduced to ammonia via a dissociative-associative path with a low limiting potential (-0.43 V). The presence of vacancies enhances the catalytic performance and the collaboration between Mo3 around the vacancies and the remaining substrate d-Mo2C facilitates the overall catalytic reaction. VC-Mo2C also well suppresses the hydrogen evolution reaction (HER) with high selectivity. The present work opens up a new way to promote the sustainable production of NH3.

Inflammation-modulating antibacterial hydrogel sustained release asiaticoside for infection wound healing.

Wound infection and persistent inflammation are considered to be the main reasons for hindering wound healing. In this study, we developed an innovative hydrogel dressing, EPL-DA/ODEX/AMs, as a platform to inhibit bacteria and inflammation and promote wound healing. Polylysine (EPL) has cationic properties and can effectively disrupt bacterial cell membranes for antibacterial purposes. Polylysine-grafted levodopa (EPL-DA) with abundant amino and catechol groups can be cross-linked with oxidized dextran through Schiff base reaction to form antibacterial hydrogels with good adhesion and mechanical properties. In addition, asiaticoside, which can effectively inhibit inflammation and promote collagen regeneration, is made into PLGA microspheres to effectively deliver asiaticoside to the wound. The innovative antibacterial hydrogel of EPL-DA/ODEX/AMs may become a competitive wound dressing for infected wound.

Analysis of the current status of community nurses' spiritual care competencies and the factors: A descriptive cross-sectional analysis.

AIM: To examine and analyze the level of spiritual care competency among community nurses. DESIGN: The study employed a cross-sectional design. METHODS: From May to July 2022, 442 nurses from community health clinics were chosen as survey respondents using the convenience sample method. The General Information Questionnaire, the version in Chinese of the Nurses' Spiritual Caregiving Awareness Scale and the Chinese version of the Spiritual Caregiving Competence Scale were used in the survey. There were 442 questionnaires distributed, 422 were collected, and the response rate was 95.4%. RESULTS: The amount of spiritual care competencies of community nurses was positively correlated with the level of spiritual awareness. Simultaneously, their level of education, religious beliefs, marital status and the degree of knowledge of spirituality were all influenced.

An engineered platform based on chitin-affinity immobilization for producing low molecular weight heparin.

Using chitin-affinity interaction between triple-functional heparinase I (Hep I) and chitin, an engineered platform was prepared to produce controllable low molecular weight heparin (LMWH). Chitin microspheres with well-defined nanofibrils were fabricated through a "bottom up" pathway. An enhanced soluble protein, ChBD-SUMO-Hep I (CSH-I), was expressed in 3L batch fermentation with a high bioactivity of 2.5×103 IU/L. Chitin binding domain (ChBD) can specifically bind to chitin in noncovalent way, which leads to the immobilization and purification of enzyme in a single step. The immobilized CSH-I was preferred over its free counterpart due to its higher tolerance to heat and pH, as well as improved shelf-life. The restraint enzyme could be reused up to 8 times to achieve a conversion yield exceeding 90%. By using the bioinspired conjugates, the qualified LMWH fractions were obtained by monitoring the degradation process with an absorbance range of 44.5-68.3 at 232nm.

Expression and characterization of an enhanced recombinant heparinase I with chitin binding domain.

Heparinase I (Hep I) can efficiently depolymerize heparin and heparin sulfate to oligosaccharides or unsaturated disaccharides, which resulted in loss of physiological function such as blood coagulation. In order to realize the immobilization of Hep I on chitin carriers, we cloned Hep I with the chitin binding domain (ChBD) as a chitin-affinity tag, and the Small Ubiquitin-like MOdifier (SUMO) linker as a solvation enhancer in different fusion sequence. DNA and protein gels suggested that 4 kinds of recombinants were successfully constructed and expressed in Escherichia coli (E. coli). And the triple functional heparinases isolated from cell lysate could be efficiently purified by chitin beads. After optimizing fermentation conditions, it gave the specific enzyme activities of 1.88±0.11, 3.69±0.45, 3.44±0.38, and 2.73±0.29IU/mg total proteins for ChBD-Hep I, ChBD-SUMO-Hep I, SUMO-ChBD-Hep I, and ChBD-Hep I-SUMO, respectively, with unfractionated heparin as substrate. The optimal reaction temperature and pH were determined to be 30°C and 7.0 for all the fusion enzymes. ChBD-SUMO-Hep I exhibited the maximum half-life (48min) at 30°C and best thermo-stability under 15-50°C. All the fusion enzymes showed broad pH-stability in the range of 5.4-9.0.