Illness uncertainty, resilience, and perceived social support among patients with moyamoya disease: a cross-sectional study.

Objective: The present study aims to investigate the levels of illness uncertainty in patients with moyamoya disease and to determine the association of socio-demographic characteristics, perceived social support and resilience with illness uncertainty in patients with moyamoya disease. Method: A cross-sectional survey using convenience sampling was conducted in two hospitals in China from August to December 2023. A socio-demographic characteristics questionnaire, the Chinese versions of Mishel's Unsurety in Disease Scale (MUIS), the Chinese version of Connor-Davidson Resilience Scale (CD-RISC), and the Chinese version of Multidimensional Scale of Perceived Social Support (MSPSS) were used to perform this research. The collected data were analyzed using SPSS 24.0 statistical software. The t-test, one-way analysis of variance (ANOVA), pearson correlation analysis and hierarchical regression analysis were used to identify associated factors. Result: A total of 263 patients with moyamoya disease were recruited in this survey. The score of illness uncertainty was at a moderate level of (100.03 ± 18.59). The present study identified a negative correlation between illness uncertainty with resilience perceived social support. Hierarchical regression analysis showed that gender, occupation, education level, resilience and perceived social support were the related factors of illness uncertainty. Conclusion: Patients with moyamoya disease experienced moderate disease uncertainty on average, which was related to gender, occupation, education level, resilience and perceived social support. Future research is needed to better explore the complex relationships between illness uncertainty, resilience, and perceived social support with different types of moyamoya disease using longitudinal research.

FoxO1-modulated macrophage polarization regulates osteogenesis via PPAR-γ signaling.

Periodontitis, a common chronic inflammatory disease, epitomizes a significant impairment in the host immune system and an imbalance of bone metabolism. Macrophage polarization, a dynamic process dictated by the microenvironment, intricately contributes to the interplay between the immune system and bone remodeling, namely the osteoimmune system. Forkhead box protein O1 (FoxO1) has been shown to play a dramatic role in mediating oxidative stress, bone mass, as well as cellular metabolism. Nevertheless, the function and underlying mechanisms of FoxO1 in regulating macrophage polarization-mediated osteogenesis in periodontitis remain to be further elucidated. Here, we found that FoxO1 expression was closely linked to periodontitis, accompanied by aggravated inflammation. Notably, FoxO1 knockdown skewed macrophage polarization from M1 to the antiinflammatory M2 phenotype under inflammatory conditions, which rescued the impaired osteogenic potential. Mechanistically, we revealed that the enhancement of the transcription of peroxisome proliferator-activated receptor (PPAR) signaling in FoxO1-knockdown macrophages. In agreement with this contention, GW9662, a specific inhibitor of PPAR-γ signaling, greatly aggravated macrophage polarization from M2 to the M1 phenotype and attenuated osteogenic potential under inflammatory conditions. Additionally, PPAR-γ signaling agonist rosiglitazone (RSG) was applied to address ligature-induced periodontitis with attenuated inflammation. Our data lend conceptual credence to the function of FoxO1 in mediating macrophage polarization-regulated osteogenesis which serves as a novel therapeutic target for periodontitis.

Do inexperienced nurses in the lactation period experience workplace violence? A qualitative study.

Introduction: Among clinical healthcare personnel, nurses face the highest proportion of workplace violence, which has a significant impact on their physical and mental well-being as well as their personal and professional lives. However, little is known about the effects of workplace violence on inexperienced breastfeeding nurses and their experiences during and after breastfeeding when they return to work. This study aimed to explore the experiences of inexperienced breastfeeding nurses who encountered workplace violence and its resulting impacts. Methods: This study employed a descriptive qualitative design. Semi-structured in-depth interviews were conducted with 20 nurses working in various positions and departments at three tertiary hospitals. Purposive and maximum variation sampling techniques were employed. The interview data were analyzed using Colaizzi's method, and the research findings were reported according to Consolidated Criteria for Reporting Qualitative Studies (COREQ)standards. Results: Inferences regarding workplace violence and risks for inexperienced breastfeeding nurses included physical labor (such as lifting heavy objects and performing cardiopulmonary resuscitation), conflicts, inadequate job skills, role confusion, occupational exposure risks, patient violence, and pressure from older adults. An inductive thematic investigation revealed the "Challenges faced during breastfeeding," "Conflicting professional and family roles," "Out of balance," and "Coping strategies." Conclusion: Inexperienced breastfeeding nurses experience several negative consequences due to workplace violence. Therefore, it is essential to plan and implement preventive strategies and management programs that specifically target workplace violence among inexperienced breastfeeding nurses.

Organoids for Cancer Research: Advances and Challenges.

As 3D culture technology advances, new avenues have opened for the development of physiological human cancer models. These preclinical models provide efficient ways to translate basic cancer research into clinical tumor therapies. Recently, cancer organoids have emerged as a model to dissect the more complex tumor microenvironment. Incorporating cancer organoids into preclinical programs have the potential to increase the success rate of oncology drug development and recapitulate the most efficacious treatment regimens for cancer patients. In this review, four main types of cancer organoids are introduced, their applications, advantages, limitations, and prospects are discussed, as well as the recent application of single-cell RNA-sequencing (scRNA-seq) in exploring cancer organoids to advance this field.

Multi-heterojunctioned plastics with high thermoelectric figure of merit.

Conjugated polymers promise inherently flexible and low-cost thermoelectrics for powering the Internet of Things from waste heat1,2. Their valuable applications, however, have been hitherto hindered by the low dimensionless figure of merit (ZT)3-6. Here we report high-ZT thermoelectric plastics, which were achieved by creating a polymeric multi-heterojunction with periodic dual-heterojunction features, where each period is composed of two polymers with a sub-ten-nanometre layered heterojunction structure and an interpenetrating bulk-heterojunction interface. This geometry produces significantly enhanced interfacial phonon-like scattering while maintaining efficient charge transport. We observed a significant suppression of thermal conductivity by over 60 per cent and an enhanced power factor when compared with individual polymers, resulting in a ZT of up to 1.28 at 368 kelvin. This polymeric thermoelectric performance surpasses that of commercial thermoelectric materials and existing flexible thermoelectric candidates. Importantly, we demonstrated the compatibility of the polymeric multi-heterojunction structure with solution coating techniques for satisfying the demand for large-area plastic thermoelectrics, which paves the way for polymeric multi-heterojunctions towards cost-effective wearable thermoelectric technologies.

Simultaneous targeting and monitoring of free antigen and in-situ membrane antigen in prostate cancer cells via an aggregation-induced emission-based bifunctional probe.

The precise clinical diagnosis of prostate cancer still presents inherent challenges, and usually a monitoring of multiple biomarkers is required. In this study, a new aggregation-induced emission (AIE)-based bifunctional strategy was developed for the simultaneous detection of prostate cancer-specific in situ membrane antigens (PSMA) and free antigens (PSA). First, a bifunctional fluorescent probe with double sensing sites (a PSA-specific sensing site and a PSMA-targeted ligand) was constructed. In the presence of PSA, it specifically binds to the PSA-specific sensing site of the probe, resulting in the restoration of the fluorescence signal, enabling linear sensing of PSA. For the detection of PSMA, the PSMA-targeted ligand modified on the probe can specifically recognize PSMA, inducing the aggregation of the AIE material and resulting in an enhanced fluorescence signal. Moreover, a liposome-based artificial cell was developed to simulate the real prostate cancer cell, and it was used to investigate the feasibility of monitoring the two types of antigens. Utilizing this bifunctional fluorescent strategy, a dual-analysis of free serum antigen biomarker of PSA and in-situ membrane antigen of PSMA was achieved. The assay exhibited a wide linearity range for PSA detection from 0.0001 to 0.1 µg/mL, with a low limit of detection (LOD) of 6.18 pg/mL. For PSMA, the obtained LOD is 8.79 pg/mL, with a linearity range from 0.0001 to 0.1 µg/mL. This strategy allows us to simultaneously assess the levels of two types of biomarkers in living human prostatic cancer cells, providing a highly accurate and selective tool for early screening and monitoring of prostatic cancer.

Bazi Bushen capsule attenuates cardiac systolic injury via SIRT3/SOD2 pathway in high-fat diet-fed ovariectomized mice.

Background: Bazi Bushen capsule (BZBS) is a Chinese herbal compound that is clinically used to treat fatigue and forgetfulness. However, it is still unclear whether and how BZBS affects heart function decline in menopausal women. This study aimed to examine the effect of BZBS on cardiac function in a high-fat diet-fed ovariectomy (HFD-fed OVX) mouse model and elucidate the underlying mechanism of this effect. Methods: The experimental animals were divided into five groups: sham group, HFD-fed OVX group, and BZBS (0.7, 1.4, 2.8 g/kg) intervention groups. Senescence ß-galactosidase staining and echocardiography were used to evaluate cardiac function. SwissTargetPrediction, KEGG and GO enrichment analyses were used to screen the underlying mechanism of BZBS. The morphological and functional changes in cardiac mitochondria and the underlying molecular mechanism were assessed by transmission electron microscopy, western blotting and biochemical assays. STRING database was used to analysis protein-protein interaction (PPI) network. Molecular docking studies were employed to predict the interactions of specific BZBS compounds with their protein targets. Results: BZBS treatment ameliorated cardiac senescence and cardiac systole injury in HFD-fed OVX mice. GO and KEGG analyses revealed that the 530 targets of the 14 main components of BZBS were enriched mainly in the oxidative stress-associated pathway, which was confirmed by the finding that BZBS treatment prevented abnormal morphological changes and oxidative stress damage to cardiac mitochondria in HFD-fed OVX mice. Furthermore, the STRING database showed that the targets of BZBS were broadly related to the Sirtuins family. And BZBS upregulated the SIRT3 and elevated the activity of SOD2 in the hearts of HFD-fed OVX mice, which was also verified in vitro. Additionally, we revealed that imperatorin and osthole from the BZBS upregulated the expression of SIRT3 by directly docking with the transcription factors HDAC1, HDAC2, and BRD4, which regulate the expression of SIRT3. Conclusion: This research shows that the antioxidative effect and cardioprotective role of BZBS on HFD-fed OVX mice involves an increase in the activity of the SIRT3/SOD2 pathway, and the imperatorin and osthole of BZBS may play central roles in this process.

Enhancing the Thermoelectric and Mechanical Properties of p-Type PbS through Band Convergence and Microstructure Regulation.

While lead sulfide shows notable thermoelectric properties, its production costs remain high, and its mechanical hardness is low, which constrains its commercial viability. Herein, we demonstrate a straightforward and cost-effective method to produce PbS nanocrystals at ambient temperature. By introducing controlled amounts of silver, we achieve p-type conductivity and fine-tune the energy band structure and lattice configuration. Computational results show that silver shifts the Fermi level into the valence band, facilitating band convergence and thereby enhancing the power factor. Besides, excess silver is present as silver sulfide, which effectively diminishes the interface barrier and enhances the Seebeck coefficient. Defects caused by doping, along with dislocations and interfaces, reduce thermal conductivity to 0.49 W m-1 K-1 at 690 K. Moreover, the alterations in crystal structure and chemical composition enhance the PbS mechanical properties. Overall, optimized materials show thermoelectric figures of merit approximately 10-fold higher than that of pristine PbS, alongside an average hardness of 1.08 GPa.

Altering the CO2 Electroreduction Pathways Towards C1 or C2+ Products via Engineering the Strength of Interfacial Cu-O Bond.

Copper (Cu)-based catalysts have established their unique capability for yielding wide value-added products from CO2. Herein, we demonstrate that the pathways of the electrocatalytic CO2 reduction reaction (CO2RR) can be rationally altered toward C1 or C2+ products by simply optimizing the coordination of Cu with O-containing organic species (squaric acid (H2C4O4) and cyclohexanehexaone (C6O6)). It is revealed that the strength of Cu-O bonds can significantly affect the morphologies and electronic structures of derived Cu catalysts, resulting in the distinct behaviors during CO2RR. Specifically, the C6O6-Cu catalysts made up from organized nanodomains shows a dominant C1 pathway with a total Faradaic efficiency (FE) of 63.7 % at -0.6 V (versus reversible hydrogen electrode, RHE). In comparison, the C4O4-Cu with an about perfect crystalline structure results in uniformly dispersed Cu-atoms, showing a notable FE of 65.8 % for C2+ products with enhanced capability of C-C coupling. The latter system also shows stable operation over at least 10 h with a high current density of 205.1 mA cm-2 at -1.0 VRHE, i.e., is already at the boarder of practical relevance. This study sheds light on the rational design of Cu-based catalysts for directing the CO2RR reaction pathway.

Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma.

Background: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma. Case presentation: A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor. Conclusion: It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Does growth hormone supplementation of in vitro fertilization/intracytoplasmic sperm injection improve cumulative live birth rates in women with poor embryonic development in the previous cycle?

BACKGROUND: Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. METHODS: This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. RESULTS: After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1-1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2-3.3). CONCLUSIONS: Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

Effects of elastic band resistance training on the physical and mental health of elderly individuals: A mixed methods systematic review.

OBJECTIVES: Elastic band resistance training in elderly individuals can improve physical fitness and promote mental health in addition to other benefits. This systematic review aimed to review, summarize, and evaluate quantitative, qualitative, and mixed methodological studies on the use of elastic band resistance training in elderly individuals, and to investigate the influence of elastic band resistance training on the physical and mental health of elderly individuals, as well as their preferences and obstacles in training. METHODS: A convergent separation approach was used to synthesize and integrate the results, specifically the mixed systematic review approach recommended by the Joanna Briggs Institute. The extensive search strategy included electronic database searches in the Cochrane Library, PubMed, Embase, Web of Science, Google Scholar, MEDLINE, and CINAHL. The researchers rigorously screened the literature, extracted and analyzed the data, and evaluated the quality of the included studies using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Twenty-eight studies were included, of which 25 were quantitative studies, 2 were qualitative studies, and 1 was a mixed-methods study. A total of 1,697 subjects were investigated across all studies. Quantitative evidence supports the notion that elastic band resistance training can improve upper and lower limb flexibility, endurance, upper strength, physical balance, and cardiopulmonary function and enhance the mental health of elderly individuals. Participants in the qualitative study reported some preferences and obstacles with band resistance training, but most participants reported physical benefits. CONCLUSIONS: Despite the heterogeneity between studies, this review is the first systematic review to comprehensively evaluate the effectiveness of elastic band resistance training in older adults. It not only shows the influence of elastic band resistance training on the physical and mental health of the elderly, but also emphasizes the preference and obstacles of elderly individuals face.

Research progress on the functions and biosynthesis of theaflavins.

Theaflavins are beneficial to human health due to various bioactivities. Biosynthesis of theaflavins using polyphenol oxidase (PPO) is advantageous due to cost effectiveness and environmental friendliness. In this review, studies on the mechanism of theaflavins formation, the procedures to screen and prepare PPOs, optimization of reaction systems and immobilization of PPOs were described. The challenges associated with the mass biosynthesis of theaflavins, such as poor enzyme activity, undesirable subproducts and inclusion bodies of recombinant PPOs were presented. Further strategies to solve these challenges and improve theaflavins production, including enzyme engineering, immobilization enzyme technology, water-immiscible solvent-water biphasic systems and recombinant enzyme technology, were proposed.

Grid-plainification enables medium-temperature PbSe thermoelectrics to cool better than Bi2Te3.

Thermoelectric cooling technology has important applications for processes such as precise temperature control in intelligent electronics. The bismuth telluride (Bi2Te3)-based coolers currently in use are limited by the scarcity of Te and less-than-ideal cooling capability. We demonstrate how removing lattice vacancies through a grid-design strategy switched PbSe from being useful as a medium-temperature power generator to a thermoelectric cooler. At room temperature, the seven-pair device based on n-type PbSe and p-type SnSe produced a maximum cooling temperature difference of ~73 kelvin, with a single-leg power generation efficiency approaching 11.2%. We attribute our results to a power factor of >52 microwatts per centimeter per square kelvin, which was achieved by boosting carrier mobility. Our demonstration suggests a path for commercial applications of thermoelectric cooling based on Earth-abundant Te-free selenide-based compounds.

FKF1b controls reproductive transition associated with adaptation to geographical distribution in maize.

Maize (Zea mays subspecies mays) is an important commercial crop across the world, and its flowering time is closely related to grain yield, plant cycle and latitude adaptation. FKF1 is an essential clock-regulated blue-light receptor with distinct functions on flowering time in plants, and its function in maize remains unclear. In this study, we identified two FKF1 homologs in the maize genome, named ZmFKF1a and ZmFKF1b, and indicated that ZmFKF1a and ZmFKF1b independently regulate reproductive transition through interacting with ZmCONZ1 and ZmGI1 to increase the transcription levels of ZmCONZ1 and ZCN8. We demonstrated that ZmFKF1b underwent artificial selection during modern breeding in China probably due to its role in geographical adaptation. Furthermore, our data suggested that ZmFKF1bHap_C7 may be an elite allele, which increases the abundance of ZmCONZ1 mRNA more efficiently and adapt to a wider range of temperature zone than that of ZmFKF1bHap_Z58 to promote maize floral transition. It extends our understanding of the genetic diversity of maize flowering. This allele is expected to be introduced into tropical maize germplasm to enrich breeding resources and may improve the adaptability of maize at different climate zones, especially at temperate region.

Five previously undescribed citrinin derivatives from the endophytic fungus Penicillium citrinum GZWMJZ-836.

Penicillium citrinum GZWMJZ-836 is an endophytic fungus from Drynaria roosii Nakaike. Five previously undescribed citrinin derivatives (1-5) and six intermediates related to their biosynthesis (6-11) were obtained from the extract of this strain's solid fermentation using multiple column chromatography separations, including high-performance liquid chromatography. The structures of these compounds were determined through comprehensive spectroscopic analyses, primarily using NMR and HRESIMS data. The stereochemistry was mainly confirmed by ECD calculations, and the configurations of C-7' in compounds 4 and 5 were determined using 13C NMR calculations. Compounds 4-5 and 8 showed antibacterial activity against five strains, with minimum inhibitory concentration values ranging from 7.8 to 125 µM. Compounds 4 and 7 exhibited inhibitions against three plant pathogenic fungi, with IC50 values ranging from 66.6 to 152.1 µM. Additionally, a putative biosynthetic pathway for compounds 1-5 derived from citrinin was proposed.

Effect of the VR-guided grasping task on the brain functional network.

Virtual reality (VR) technology has been demonstrated to be effective in rehabilitation training with the assistance of VR games, but its impact on brain functional networks remains unclear. In this study, we used functional near-infrared spectroscopy imaging to examine the brain hemodynamic signals from 18 healthy participants during rest and grasping tasks with and without VR game intervention. We calculated and compared the graph theory-based topological properties of the brain networks using phase locking values (PLV). The results revealed significant differences in the brain network properties when VR games were introduced compared to the resting state. Specifically, for the VR-guided grasping task, the modularity of the brain network was significantly higher than the resting state, and the average clustering coefficient of the motor cortex was significantly lower compared to that of the resting state and the simple grasping task. Correlation analyses showed that a higher clustering coefficient, local efficiency, and modularity were associated with better game performance during VR game participation. This study demonstrates that a VR game task intervention can better modulate the brain functional network compared to simple grasping movements and may be more beneficial for the recovery of grasping abilities in post-stroke patients with hand paralysis.

Analysis of Fever Following Bronchoscopy and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Objective: Bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are two essential methods for obtaining the pathological diagnosis of central lung masses or hilar and mediastinal lymphadenopathy. We can observe that many patients have a fever after examinations, but the pathogenesis is not yet fully clear. We tried to comprehensively assess the occurrence of postoperative fever and bacterial infections in patients undergoing bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) procedures. Methods: We retrospectively analyzed 512 patients undergoing bronchoscopy or EBUS-TBNA examination. According to examination methods, all patients were classified into three groups: Only perform bronchoscopy examination (BO) group (122 cases)，both perform bronchoscopy and biopsy (BB) group (262 cases), and EBUS-TBNA after bronchoscopy (EBUS) group (128 cases). Peripheral blood leucocyte, neutrophil count, and serum IL-6 test results were obtained before and after the examination. A blood culture was performed when the body temperature was higher than 38.5°C. Results: Among the three groups, the onset time (5.5h), average duration (6h), and peak temperature (37.7°C) of fever in the BO group were lower than those in the BB and EBUS groups. Still, there was no significant difference in onset time (11.66h, 11.83h), average duration (12.86h, 13.56h), and peak temperature (39.1°C, 39.1°C) between the BB group and EBUS group. There was no significant difference in the peripheral blood leukocyte count, neutrophil count or IL-6 level before the operation (P > .05). Compared with the preoperative, the leukocyte count, neutrophil count and IL-6 level in the three groups were increased after the operation (P < .05). Positive blood cultures were diagnosed as normal oropharyngeal flora. Conclusions: Postoperative fever after bronchoscopy is a relatively common complication, most of which do not require special treatment. Individuals with concomitant diseases such as diabetes may have postoperative infections after EBUS-TBNA, and they should be emphatically observed. The findings could potentially extend to similar diagnostic procedures or situations in pulmonary medicine. Understanding the risk factors associated with postoperative fever can help healthcare providers manage patient expectations and monitor certain groups more closely.

MicroRNA-195 liposomes for therapy of Alzheimer's disease.

The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood-brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/miR-195 complex (DPMT@PEI/miR-195) that was engineered through dual modifications to contain P-aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/miR-195 or donepezil alone. Furthermore, DPMT@PEI/miR-195 effectively attenuated the positive signals of Aß, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.

Indole Diterpene Derivatives from the Aspergillus flavus GZWMJZ-288, an Endophytic Fungus from Garcinia multiflora.

A new indole diterpene, 26-dihydroxyaflavininyl acetate (1), along with five known analogs (2-6) were isolated from the liquid fermentation of Aspergillus flavus GZWMJZ-288, an endophyte from Garcinia multiflora. The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds 1, 4, and 6 have a good binding affinity with NPC1L1, among which compound 6 exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound 5 showed inhibitory activity against α-glucosidase with an IC50 value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and α-glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.