Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

A sodium alginate - silk fibroin biosponge loaded with thrombin: Effective hemostasis and wound healing.

In trauma first aid, rapid hemostasis is a priority, extricating patients from hemorrhagic shock and infection risks. This paper explores novel hemostatic materials, using ion-crosslinking and freeze-drying techniques. Iterative experiments determined optimal conditions for the temperature-variable mixing-freeze-drying chemical reaction of sodium alginate (SA)/silk fibroin (SF). We used SA, SA/SF, SA/SF-TB and commercial hemostatic sponge control samples to perform hemostasis experiments on rat liver injury and femoral artery injury models, and to perform wound healing experiments on rat back full-layer skin. The results showed that the hemostatic time and blood loss of SA/SF-TB group rats (liver hemorrhage model: 397.17 ± 34.80 mg, 77.83 ± 7.41 s; Femoral artery bleeding model: 940.33 ± 41.93 mg, 96.83 ± 4.07 s) was significantly better than other experimental groups, and similar to the commercial group. The wound healing experiment showed that the new granulation tissue thickness of SA/SF-TB group was thicker (380.39 ± 28.56 µm) at day 14. In addition, the material properties and biocompatibility of sponges were characterized by cell experiments and in vivo embedding experiments. All the results showed that the SA/SF-TB hemostatic sponge prepared in this study could not only seal the wound quickly and stop bleeding, but also promote the growth of epidermal cells and fibroblasts and accelerate wound healing. This new material solves the shortcomings of traditional materials such as low stability, limited shelf life, high unit price, and has good biocompatibility, easy preparation, rapid hemostasis and other excellent properties. Therefore, this innovative hemostatic material has great prospects and potential in clinical applications.

A penicillinase-modified poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel biosensor with superior recyclability for sensitive and colorimetric detection of penicillin G.

Antibiotics are widely used for treating bacterial infections. However, excessive or improper use of antibiotics can pose a serious threat to human health and water environments, and thus, developing cost-effective, portable and effective strategies to analyze and detect antibiotics is highly desired. Herein, we reported a responsive photonic hydrogel (RPH)-based optical biosensor (PPNAH) with superior recyclability for sensitive and colorimetric determination of a typical ß-lactam antibiotic penicillin G (PG) in water. This sensor was composed of poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel with incorporated penicillinase and Fe3O4@SiO2 colloidal photonic crystals (CPCs). The sensor could translate PG concentration signals into changes in the diffraction wavelength and structural color of the hydrogel. It possessed high sensitivity and selectivity to PG and excellent detection performances for other two typical ß-lactam antibiotics. Most importantly, due to the unique thermosensitivity of the poly(N-isopropylacrylamide) moieties in the hydrogel, the PG-responded PPNAH sensor could be facilely regenerated via a simple physical method at least fifty times while without compromising its response performance. Besides, our sensor was suitable for monitoring the PG-contaminated environmental water and displayed satisfactory detection performances. Such a sensor possessed obvious advantages of superior recyclability, highly chemical stability, low production cost, easy fabrication, wide range of visual detection, simple and intuitive operation for PG detection, and environmental-friendliness, which holds great potential in sensitive and colorimetric detection of the PG residues in polluted water.

Environmental Evaluation on Toxicity, Toxic Mechanism, and Hydrolysis Behavior of Potential Acethydrazide Fungicide Candidates.

The evaluation of toxicity and environmental behavior of bioactive lead molecules is helpful in providing theoretical support for the development of agrochemicals, in line with the sustainable development of the ecological environment. In previous work, some acethydrazide structures have been demonstrated to exhibit excellent and broad-spectrum fungicidal activity; however, its environmental compatibility needs to be further elucidated if it is to be identified as a potential fungicide. In this project, the toxicity of fungicidal acethydrazide lead compounds F51, F58, F72, and F75 to zebrafish was determined at 10 µg mL-1 and 1 µg mL-1. Subsequently, the toxic mechanism of compound F58 was preliminarily explored by histologic section and TEM observations, which revealed that the gallbladder volume of common carp treated with compound F58 increased, accompanied by a deepened bile color, damaged plasma membrane, and atrophied mitochondria in gallbladder cells. Approximately, F58-treated hepatocytes exhibited cytoplasmic heterogeneity, with partial cellular vacuolation and mitochondrial membrane rupture. Metabolomics analysis further indicated that differential metabolites were enriched in the bile formation-associated steroid biosynthesis, primary bile acid biosynthesis, and taurine and hypotaurine metabolism pathways, as well as in the membrane function-related glycerophospholipid metabolism, linolenic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism pathways, suggesting that the acethydrazide F58 may have acute liver toxicity to common carp. Finally, the hydrolysis dynamics of F58 was investigated, with the obtained half-life of 5.82 days. The above results provide important guiding significance for the development of new green fungicides.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.

SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases.

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.

Kaolin loaded gelatin sponges for rapid and effective hemostasis and accelerated wound healing.

Severe trauma with massive active blood loss, including liver and spleen rupture, arterial bleeding and pelvic fracture, will lead disability, malformation and even death. Therefore, it is very important to develop new, fast and efficient hemostatic materials. In this study, a novel Gelatin/Kaolin (GE/KA) composite sponge was developed. Meanwhile, to further investigate the effect of kaolin content on sponge properties, we prepared four types of sponges: GE/5% KA, GE/10% KA, GE/15% KA and GE/20% KA. The results of coagulation test in vitro showed that compared to the other groups, there were more activated adhered platelets and red blood cells on the surface of GE/15% KA. The results of hemostasis test in vivo showed that compared to other experimental groups, the GE/15% KA group had significantly less hemostasis time (liver hemostasis model: 69.50 ± 2.81 s; femoral artery hemostasis model: 75.17 ± 3.06 s) and bleeding volume (liver hemostasis model: 219.02 ± 10.39 mg; femoral artery hemostasis model: 948.00 ± 50.69 mg), and was similar to the commercial hemostasis material group. Additionally, the material properties of the sponge were characterized and its biocompatibility was verified as well through cell experiments and in vivo embedding experiments. All these results indicate that the optimal content of kaolin is 15%, which provides a theoretical basis for subsequent research. All in all, the novel GE/KA composite sponge prepared in this study can be used as a multifunctional hemostatic wound dressing for the treatment of complex wounds under various trauma scenes.

Circ-Luc7l Absence Attenuates Diabetic Nephropathy Progression by Reducing Mesangial Cell Excessive Proliferation, Inflammation, and Extracellular Matrix Accumulation via Mediating the miR-205-5p/Tgfbr1 Pathway.

Diabetic nephropathy (DN) threatens the survival quality of patients, with complex pathogenesis. Circular RNA (circRNA) dysregulation occurs in DN development. This work aimed to investigate the role of circ-Luc7l in DN cell models and related molecular mechanisms. The expression of circ-Luc7l, microRNA (miR)-205-5p, and transforming growth factor-beta receptor 1 (Tgfbr1) was examined by real-time quantitative PCR (RT-qPCR). Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) assay and EdU assay. The expression of extracellular matrix (ECM)-related markers and Tgrbr1 protein was measured by Western blot. The binding between miR-205-5p and circ-Luc7l or Tgfbr1 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay. Experimental animal models were established to elucidate the function of circ-Luc7l in vivo. Circ-Luc7l expression was notably enhanced in high glucose (HG)-treated mesangial cells. Knockdown of circ-Luc7l attenuated HG-induced cell proliferation, inflammation, and ECM accumulation in vitro and relieved inflammation and ECM accumulation of kidneys of diabetic mice in vivo. Circ-Luc7l targeted miR-205-5p, and miR-205-5p inhibition rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. MiR-205-5p bound to Tgfbr1 whose expression was negatively regulated by circ-Luc7l. Tgfbr1 overexpression also rescued the depletion effects of circ-Luc7l knockdown on cell proliferation, inflammation, and ECM accumulation. In HG conditions, increased circ-Luc7l upregulated Tgfbr1 expression via targeting miR-205-5p to induce DN progression.

Design and impact assessment of policies to overcome oversupply in China's national carbon market.

China has adopted a national carbon emissions trading market to promote emission reductions, but until now, overallocation of allowances suffer low carbon prices and thus to unfulfilled emission reduction goals. We report a general equilibrium modeling that indicates the flexible compliance and price adjustment mechanism of the carbon market, along with explores the solution to the oversupply of allowances in the China's national carbon market. We find that, under the current policy, the initial loose allowance allocation decreases the overall carbon price, and simultaneously the total amount of banked carbon allowances reaches 4.880 billion tons in 2030, resulting in the level of carbon price cannot achieve NDC (Nationally Determined Contribution) targets. However, by introducing carbon market price adjustment schemes, we observe that the cumulative amount of allowances can effectively reduce, enabling the carbon price rising. Importantly, the amount of the supply of allowances decreases most under the benchmark decrease scenario, which increases the emission reduction pressure of the enterprises from the beginning, leading to the largest economic losses, the price-based adjustment mechanism raises the carbon price to expected level at the minimize economic losses, and the quantity-based adjustment mechanism is more sensitive to policy parameters compared to the price -based adjustment mechanism. These findings offer a promising avenue for selecting cost-effective price adjustment mechanism to improve price mechanism design for national carbon markets.

[Effect of Using Hydrogen Peroxide for Periodic Disinfection Combined With Continuous Disinfection to Control Contamination in Dental Unit Waterline]. / è¿‡æ°§åŒ–æ°¢å®šæœŸæ¶ˆæ¯’ç»“åˆæŒç»­æ¶ˆæ¯’å¯¹å£è ”ç»¼åˆæ²»ç–—å°æ°´è·¯æ±¡æŸ“æŽ§åˆ¶çš„æœ‰æ•ˆæ€§è§‚å¯Ÿ.

Objective: To observe the effect of using hydrogen peroxide in periodic disinfection combining with continuous disinfection of dental unit waterlines and to provide references for the selection of waterway disinfection measures. Methods: A total of 4 dental units in a hospital of stomatology were selected through convenience sampling. The dental unit waterlines received periodic disinfection once every 4 weeks in addition to continuous disinfection (When the dental units were not used for more than 3 days, an additional periodic disinfection would be performed.). Periodic disinfection referred to filling up the waterlines with a disinfectant solution (1.4% hydrogen peroxide) by using the waterline disinfection device that came with the dental unit, immersing for 24 hours, and then emptying out the disinfectant solution. Continuous disinfection referred to using hydrogen peroxide at a concentration of 0.014% as dental treatment water and using it to flush the waterlines for 2 minutes before any dental treatment in the morning and to flush the waterlines for 30 seconds after each dental treatment. The study lasted for 25 weeks, with periodic disinfection being performed for 7 times and continuous disinfection carried out for the rest of the dental treatment time. During the 25 weeks, water samples were collected from air/water syringes and high-speed handpieces. Then, the water samples were incubated and the bacterial concentration and the qualification rates were calculated accordingly. When the bacterial concentration≤100 CFU/ mL, the water samples were considered to be qualified. Waterline tubes of 1 cm were collected before and after the 25 weeks of disinfection with hydrogen peroxide. Biofilms in the waterline tube were observed under scanning electron microscope. Results: A total of 352 water samples were collected. Eight water samples were collected before disinfection with hydrogen peroxide, with the median of bacterial concentration being 3140 CFU/mL. On the first day of disinfection with hydrogen peroxide, the median bacterial concentration in dental treatment water was 7.5 CFU/mL. There was a significant difference between the bacterial concentration of the water samples before the disinfection and that after the disinfection (P=0.012). A total of 344 water samples were collected after the disinfection, with the median bacterial concentrations for air/water syringes and high-speed handpieces being 11 CFU/mL and 11CFU/mL and the qualified rates being 83.7% and 82.0%, respectively. There was no significant difference in bacterial concentration or the qualification rates. During week 1 through week 9 of the disinfection, the qualification rates of the dental treatment water always exceeded 80% in 8 weeks, with week 3 being the exception. In the two four-week disinfection periods of week 14 through week 17 and week 18 through week 21, the qualification rate was maintained at above 80% for only the first two weeks and started to decrease from the third week. Biofilm morphology was observed under scanning electron microscope. Before the disinfection, the biofilm was found to be a dense structure and the mixture of a large number of bacteria. After 25 weeks of the disinfection, the biofilm structure appeared to be loose and did not show consistent characteristics of a large number of bacteria retained. Conclusion: Periodic disinfection combined with continuous disinfection using hydrogen peroxide can effectively control contamination in dental unit waterlines. But the cycles of periodic disinfection and the concentration of hydrogen peroxide for continuous disinfection should be further discussed according to the actual clinical situation.

Adverse effects of unilateral transfemoral amputation on para-alpine sit skiers and mitigation methods.

OBJECTIVES: This study aimed to evaluate the adverse effects of unilateral transfemoral amputation on neuromuscular and kinematic parameters in alpine sit skiers, and to determine if additional restraints on the human-bucket interface could help mitigate the effects. DESIGN: Cross-sectional, repeated measures study. METHODS: Simulated skiing tests were conducted indoors involving 10 skiers with unilateral transfemoral amputation and 10 able-bodied participants. A Paralympic silver medalist performed slalom skiing tests on snow. These tests were conducted with and without additional strapping on the residual limb. Surface electromyography of trunk muscles and athletic performance was measured, and the asymmetry index was calculated. RESULTS: Athletes were significantly dependent on muscle activation on the dominant side (asymmetry index = 7.8 %-28.3 %, p < 0.05). Worse athletic performance to the dominant side was found based on inclination angles of the indoor board (asymmetry index = -9.8 %, p = 0.014) and outdoor sit ski (-11.1 %, p = 0.006), and distance to the gate poles during skiing turns (18.6 %, p < 0.001). After using additional restraints, the above asymmetry index declined significantly (asymmetry index < 4.5 %, p < 0.05). Furthermore, athletic performance was significantly improved on both body sides by 11.1 %-30.7 % (p < 0.05). CONCLUSIONS: Unilateral transfemoral amputation caused the dependence on the trunk muscles of the dominant side and the corresponding unilateral poor performance in athletes. Adjusting restraints in the human-equipment interface by additional strapping could mitigate the asymmetry issues and improve athletic performance.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

Multi-Scale Attention Network for Building Extraction from High-Resolution Remote Sensing Images.

The precise building extraction from high-resolution remote sensing images holds significant application for urban planning, resource management, and environmental conservation. In recent years, deep neural networks (DNNs) have garnered substantial attention for their adeptness in learning and extracting features, becoming integral to building extraction methodologies and yielding noteworthy performance outcomes. Nonetheless, prevailing DNN-based models for building extraction often overlook spatial information during the feature extraction phase. Additionally, many existing models employ a simplistic and direct approach in the feature fusion stage, potentially leading to spurious target detection and the amplification of internal noise. To address these concerns, we present a multi-scale attention network (MSANet) tailored for building extraction from high-resolution remote sensing images. In our approach, we initially extracted multi-scale building feature information, leveraging the multi-scale channel attention mechanism and multi-scale spatial attention mechanism. Subsequently, we employed adaptive hierarchical weighting processes on the extracted building features. Concurrently, we introduced a gating mechanism to facilitate the effective fusion of multi-scale features. The efficacy of the proposed MSANet was evaluated using the WHU aerial image dataset and the WHU satellite image dataset. The experimental results demonstrate compelling performance metrics, with the F1 scores registering at 93.76% and 77.64% on the WHU aerial imagery dataset and WHU satellite dataset II, respectively. Furthermore, the intersection over union (IoU) values stood at 88.25% and 63.46%, surpassing benchmarks set by DeepLabV3 and GSMC.

Self-powered photoelectrochemical immunosensing platform for sensitive CEA detection using dual-photoelectrode synergistic signal amplification.

Self-powered photoelectrochemical (PEC) sensing, as an emerging sensing mode, can effectively solve the problems such as weak anti-interference ability and poor signal response of individual photoanode or photocathode sensing. In this work, an ITO/Co-CuInS2 photocathode and ITO/WO3@CdS photoanode based self-powered cathodic PEC immunosensor was developed, which integrated dual-photoelectrode to synergistic amplify the signal for highly sensitive and specific detection of carcinoembryonic antigen (CEA). The self-powered PEC sensor could drive electrons transfer through the difference in Fermi levels between the two photoelectrodes without an external bias voltage. The photoanode was introduced to amplify the photoelectric signal, and the photocathode was only designed for the construction of sensing interfaces. The proposed sensor quantitatively determined the target CEA with the detection limit of 0.23 pg/mL and a linear correlation confine of 0.1 pg/mL ∼100 ng/mL. The constructed immunosensing platform exhibited high sensitivity, satisfactory stability and great biological detection selectivity, providing a feasible and effective strategy for the manufacture of new self-powered sensors in high-performance PEC bioanalytical applications.

Effective bandgap narrowing and enhanced optoelectronic performance of Cs2PtBr6 double perovskites by pressure engineering.

Tuning the structure-property relations of perovskites by pressure engineering holds great promise for discovering materials with favorable properties. The newly synthesized Cs2PtBr6 double perovskite exhibits excellent water resistance and chemical stability. Yet its photoelectric conversion efficiency is limited by its intrinsic wide-bandgap nature. In this work, based on density functional theory calculations, we demonstrate the bandgap narrowing of Cs2PtBr6 via pressure engineering and maintain its structural stability. Strikingly, upon applying pressure up to 12 GPa, the bandgap value decreases to 1.34 eV, which exactly reaches the optimal bandgap required by the Shockley-Queisser efficiency limit. Moreover, optical calculation analysis shows that the optical absorption of Cs2PtBr6 exhibits a significant improvement within the visible range. Therefore, the potential of Cs2PtBr6 as a photovoltaic material by pressure engineering is improved. This work is useful for designing and synthesizing new perovskite materials with enhanced performance.

Effects of vitamins and polyunsaturated fatty acids on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

PURPOSE: Vitamins and polyunsaturated fatty acids (PUFAs) have been studied extensively as safe and manageable nutrient interventions for mild cognitive impairment (MCI). The purpose of the current meta-analysis was to examine the effects of vitamins and PUFAs on cognition and to compare the effects of single and multiple nutrient subgroups in patients with MCI. METHODS: Randomized controlled trials (RCTs) written in English and Chinese were retrieved from eight databases, namely, PubMed, CENTRAL, Embase, CINAHL, Web of Science, SinoMed, CNKI, and Wanfang Data, from their respective dates of inception until 16 July 2023. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool 2.0. Meta-analyses were performed to determine the standardized mean differences (SMDs) in global cognitive function, memory function, attention, visuospatial skills, executive function, and processing speed between the supplement and control groups using 95% confidence intervals (CI) and I2. Prospero registration number: CRD42021292360. RESULTS: Sixteen RCTs that studied different types of vitamins and PUFAs were included. The meta-analysis revealed that vitamins affected global cognitive function (SMD = 0.58, 95% CI = [0.20, 0.96], P = 0.003), memory function (SMD = 2.55, 95% CI = [1.01, 4.09], P = 0.001), and attention (SMD = 3.14, 95% CI = [1.00, 5.28], P = 0.004) in patients with MCI, and PUFAs showed effects on memory function (SMD = 0.65, 95% CI = [0.32, 0.99], P < 0.001) and attention (SMD = 2.98, 95% CI = [2.11, 3.84], P < 0.001). Single vitamin B (folic acid [FA]: SMD = 1.21, 95% CI = [0.87, 1.55]) supplementation may be more effective than multiple nutrients (FA and vitamin B12: SMD = 0.71, 95% CI = [0.41, 1.01]; and FA combined with docosahexaenoic acid [DHA]: SMD = 0.58, 95% CI = [0.34, 0.83]) in global cognitive function. CONCLUSIONS: FA, vitamin B6, vitamin B12, and vitamin D may improve global cognitive function, memory function, and attention in patients with MCI. Eicosapentaenoic acid (EPA) and DHA may improve memory function and attention. We also noted that FA may exert a greater effect than a vitamin B combination (FA and vitamin B12) or the combination of FA and DHA. However, because of the low evidence-based intensity, further trials are necessary to confirm these findings.

The impact of gut microbial signals on hematopoietic stem cells and the bone marrow microenvironment.

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the bone marrow microenvironment, including mechanical properties, inflammatory signals, bone marrow stromal cells, and metabolites. Furthermore, we discuss the involvement of the gut microbiota in the development of hematologic malignancies, such as leukemia, multiple myeloma, and lymphoma.