Moderating effect of a sodium-rich diet on the association between long-term exposure to fine particulate matter and blood lipids in children and adolescents.

BACKGROUND: Several studies reported that exposure to higher levels of fine particulate matter (PM2.5) was associated with deteriorated lipid profiles in children and adolescents. However, whether a sodium-rich diet could modify the associations remains unknown. We aimed to examine the associations of long-term exposure to PM2.5 with blood lipids in children and adolescents, and further examine the effect modification by dietary and urinary sodium levels based on a multi-community population in China. METHODS: The 3711 study participants were from a cross-sectional study, which interviewed children and adolescents aged 6 to 17 years across Sichuan Province, China between 2015 and 2017. Blood lipid outcomes including blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were assessed. Information on daily dietary sodium consumption was estimated with a semi-quantitative food frequency questionnaire (FFQ), and urinary sodium was used as an internal exposure biomarker. A linear regression model was applied to estimate the associations of prior 2-years' average exposure to ambient PM2.5 with blood lipids. The effect modification by dietary and urinary sodium was examined by stratified analyses. RESULTS: The participants from rural areas had higher levels of daily sodium consumptions. The results of multivariable regression analysis indicated that per 10 µg/m3 incremental change in PM2.5 was associated with a 1.56% (95% confidence interval 0.90%-2.23%) and a 2.26% (1.15%-3.38%) higher blood TC and LDL-C levels, respectively. Among the study participants with higher levels of dietary sodium or urinary sodium, exposure to higher levels of PM2.5 was significantly associated with deteriorated lipid profiles. For example, each 10 µg/m3 incremental change in exposure to PM2.5 was correlated with a 2.83 (-4.65 to -0.97) lower percentage decrease in blood HDL-C levels among the participants who were from the highest quartile of urinary sodium levels. While, these associations changed to be nonsignificant in the participants who were from the lowest quartile of dietary sodium levels. CONCLUSION: Exposure to higher levels of PM2.5 was associated with deteriorated blood lipid levels in children and adolescents. It is noteworthy that these associations might be ameliorated through the adoption of a low-sodium dietary regimen.

Surface Display of Duck Hepatitis A Virus Type 1 VP1 Protein on Bacillus subtilis Spores Elicits Specific Systemic and Mucosal Immune Responses on Mice.

Duck viral hepatitis, primarily caused by duck hepatitis A virus type 1 (DHAV-1), poses a significant threat to the global duck industry. Bacillus subtilis is commonly utilized as a safe probiotic in the development of mucosal vaccines. In this study, a recombinant strain of B. subtilis, designated as B. subtilis RV, was constructed to display the DHAV-1 capsid protein VP1 on its spore surface using the outer coat protein B as an anchoring agent. The immunogenicity of this recombinant strain was evaluated in a mouse model through mixed feeding immunization. The results indicated that B. subtilis RV could elicit specific systemic and mucosal immune responses in mice, as evidenced by the high levels of serum IgG, intestinal secretory IgA, and potent virus-neutralizing antibodies produced. Furthermore, the recombinant strain significantly upregulated the expression levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ in the intestinal mucosa. Thus, the recombinant strain maintained the balance of the Th1/Th2 immune response and demonstrated an excellent mucosal immune adjuvant function. In summary, this study suggests that B. subtilis RV can be a novel alternative for effectively controlling DHAV-1 infection as a vaccine-based feed additive.

Tracing fossil-based plastics, chemicals and fertilizers production in China.

Phasing down fossil fuels is crucial for climate mitigation. Even though 80-90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China's respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China's emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

Evaluation of the Immunity Responses in Mice to Recombinant Bacillus subtilis Displaying Newcastle Disease Virus HN Protein Truncations.

Bacillus subtilis, a probiotic bacterium with engineering potential, is widely used for the expression of exogenous proteins. In this study, we utilized the integrative plasmid pDG364 to integrate the hemagglutinin-neuraminidase (HN) gene from Newcastle disease virus (NDV) into the genome of the B. subtilis 168 model strain. We successfully constructed a recombinant B. subtilis strain (designated B. subtilis RH) that displays a truncated HN antigen fragment on the surface of its spores and further evaluated its immunogenic effects in mice. Using ELISA, we quantified the levels of IgG in serum and secretory IgA (sIgA) in intestinal contents. The results revealed that the recombinant B. subtilis RH elicited robust specific mucosal and humoral immune responses in mice. Furthermore, B. subtilis RH demonstrated potential mucosal immune adjuvant properties by fostering the development of immune organs and augmenting the number of lymphocytes in the small intestinal villi. Additionally, the strain significantly upregulated the relative expression of inflammatory cytokines such as IL-1ß, IL-6, IL-10, TNF-α, and IFN-γ in the small intestinal mucosa. In conclusion, the B. subtilis RH strain developed in this study exhibits promising mucosal immunogenic effects. It holds potential as a candidate for an anti-NDV mucosal subunit vaccine and offers a novel preventive strategy for the poultry industry against this disease.

Evaluation of probiotic properties of a Brevibacillus laterosporus strain.

Brevibacillus laterosporus is a strain of probiotic bacteria that has been widely used in pest control, cash crop, and other production areas. However, few studies have been conducted on its use as a feed additive in animals. Therefore, the probiotic potential of B. laterosporus PBC01 was evaluated by characterizing hydrophobicity, auto-aggregation activity, bile salt and simulated gastrointestinal fluid tolerance, bienzymatic, and antibacterial activity. Antibiotic susceptibility, hemolysis assays, and supplemental feeding of mice were also performed to evaluate safety features. Our results showed that B. laterosporus PBC01 had moderate hydrophobicity, high auto-agglutination ability. Meanwhile, B. laterosporus PBC01 had good tolerance to bile salt and simulated gastrointestinal fluid. It had the ability to secrete protease, cellulase, and to inhibit various pathogens. In addition, B. laterosporus PBC01 was sensitive to many antibiotics, and did not produce hemolysin. In the safety assessment of mice, it did not cause any deaths, nor did it affect the cell components of blood, antioxidant capacity, and reproductive health. The study indicated the great probiotic characteristics and safety of B. laterosporus PBC01. This may provide a theoretical basis for the clinical application and development of probiotic-based feed additives.

Multiscale NIR-II Imaging-Guided Brain-Targeted Drug Delivery Using Engineered Cell Membrane Nanoformulation for Alzheimer's Disease Therapy.

Effective drug delivery in the central nervous system (CNS) needs to have long blood-circulation half-lives, to pass through the blood-brain barrier (BBB), and subsequently to be taken up by target cells. Herein, a traceable CNS delivery nanoformulation (RVG-NV-NPs) is developed by encapsulating bexarotene (Bex) and AgAuSe quantum dots (QDs) within Lamp2b-RVG-overexpressed neural stem cell (NSC) membranes. The high-fidelity near-infrared-II imaging by AgAuSe QDs offers a possibility of in vivo monitoring the multiscale delivery process of the nanoformulation from the whole-body to the single-cell scale. It was revealed the synergy of acetylcholine receptor-targeting of RVG and the natural brain-homing and low immunogenicity of NSC membranes prolong the blood circulation, facilitate BBB crossing and nerve cell targeting of RVG-NV-NPs. Thus, in Alzheimer's disease (AD) mice, the intravenous delivery of as low as 0.5% of oral dose Bex showed highly effective up-regulation of the apolipoprotein E expression, resulting rapid alleviation of ∼40% ß-amyloid (Aß) level in the brain interstitial fluid after a single dose administration. The pathological progression of Aß in AD mice is completely suppressed during a 1 month treatment, thus effectively protecting neurons from Aß-induced apoptosis and maintaining the cognitive abilities of AD mice.

Single-particle fluorescence tracking combined with TrackMate assay reveals highly heterogeneous and discontinuous lysosomal transport in freely orientated axons.

Axonal transport plays a significant role in the establishment of neuronal polarity, axon growth, and synapse formation during neuronal development. The axon of a naturally growing neuron is a highly complex and multifurcated structure with a large number of bends and branches. Nowadays, the study of dynamic axonal transport in morphologically complex neurons is greatly limited by the technological barrier. Here, a sparse gene transfection strategy was developed to locate fluorescent mCherry in the lysosome of primary neurons, thus enabling us to track the lysosome-based axonal transport with a single-particle resolution. Thereby, several axonal transport models were observed, including the forward or backward transport model, stop-and-go model, repeated back-and-forth transport model, and cross-branch transport model. Then, the accurate single-particle velocity quantification by TrackMate revealed a highly heterogeneous and discontinuous transportation process of lysosome-based axonal transport in freely orientated axons. And, multiple physical factors, such as the axonal structure and the size of particles, were disclosed to affect the velocity of particle transporting in freely orientated axons. The combined single-particle fluorescence tracking and TrackMate assay can be served as a facile tool for evaluating axonal transport in neuronal development and axonal transport-related diseases.

Linear-branched poly(ß-amino esters)/DNA nano-polyplexes for effective gene transfection and neural stem cell differentiation.

Controllable regulation of stem cell differentiation is a critical concern in stem cell-based regenerative medicine. In particular, there are still great challenges in controlling the directional differentiation of neural stem cells (NSCs) into neurons. Herein, we developed a novel linear-branched poly(ß-amino esters) (S4-TMPTA-BDA-DT, STBD) through a two-step reaction. The synthesized linear-branched polymers possess multiple positively charged amine terminus and degradable intermolecular ester bonds, thus endowing them with excellent properties such as high gene load, efficient gene delivery, and effective gene release and transcription in cells. In the mCherry transfection test, a high transfection efficiency of approximately 70% was achieved in primary NSCs after a single transfection. Moreover, STBD also showed high biocompatibility to NSCs without disturbing their viability and neural differentiation. With the high gene delivery property, STBD is capable of delivering siRNA (shSOX9) expression plasmid into NSCs to significantly interfere with the expression of SOX9, thus enhancing the neuronal differentiation and maturation of NSCs. The STBD/DNA nano-polyplex represents a powerful non-viral approach of gene delivery for manipulating the differentiation of stem cells, showing broad application prospects in NSC-based regenerative therapy for treating neurodegenerative diseases.

A Nanoformulation-Mediated Multifunctional Stem Cell Therapy with Improved Beta-Amyloid Clearance and Neural Regeneration for Alzheimer's Disease.

Alzheimer's disease (AD) is a common dementia that is currently incurable. The existing treatments can only moderately relieve the symptoms of AD to slow down its progress. How to achieve effective neural regeneration to ameliorate cognitive impairments is a major challenge for current AD treatment. Here, the therapeutic potential of a nanoformulation-mediated neural stem cell (NSC) therapy capable of simultaneous Aß clearance and neural regeneration is investigated in a murine model. Genetically engineered NSCs capable of stably and continuously expressing neprilysin (NEP) are developed to enhance Aß degradation and NSC survival in the brain. A PBAE-PLGA-Ag2 S-RA-siSOX9 (PPAR-siSOX9) nanoformulation with high gene/drug deliverability is synthesized to overcome AD microenvironment-associated adverse effects and to promote neuronal differentiation of the NEP-expressing NSCs. For achieving accurate stereotactic transplantation, Ag2 S quantum-dot-based fluorescence imaging is used to guide NSC transplantation in real time. This strategy shows numerous benefits, including efficient and long-lasting Aß degradation, improved neural regeneration, and accurate cell transplantation. It is shown that a single administration of this therapy achieves long-term efficacy (6 months) with respect to memory reversal and improvement of learning deficits.

Advanced Near-Infrared Light for Monitoring and Modulating the Spatiotemporal Dynamics of Cell Functions in Living Systems.

Light-based technique, including optical imaging and photoregulation, has become one of the most important tools for both fundamental research and clinical practice, such as cell signal sensing, cancer diagnosis, tissue engineering, drug delivery, visual regulation, neuromodulation, and disease treatment. In particular, low energy near-infrared (NIR, 700-1700 nm) light possesses lower phototoxicity and higher tissue penetration depth in living systems as compared with ultraviolet/visible light, making it a promising tool for in vivo applications. Currently, the NIR light-based imaging and photoregulation strategies have offered a possibility to real-time sense and/or modulate specific cellular events in deep tissues with subcellular accuracy. Herein, the recent progress with respect to NIR light for monitoring and modulating the spatiotemporal dynamics of cell functions in living systems are summarized. In particular, the applications of NIR light-based techniques in cancer theranostics, regenerative medicine, and neuroscience research are systematically introduced and discussed. In addition, the challenges and prospects for NIR light-based cell sensing and regulating techniques are comprehensively discussed.

Bioactive Dibenzo-α-pyrone Derivatives from the Endophytic Fungus Rhizopycnis vagum Nitaf22.

Six new dibenzo-α-pyrones, rhizopycnolides A (1) and B (2) and rhizopycnins A-D (3-6), together with eight known congeners (7-14), were isolated from the endophytic fungus Rhizopycnis vagum Nitaf22 obtained from Nicotiana tabacum. The structures of the new compounds were unambiguously elucidated using NMR, HRESIMS, TDDFT ECD calculation, and X-ray crystallography data. Rhizopycnolides A (1) and B (2) feature an uncommon γ-butyrolactone-fused dibenzo-α-pyrone tetracyclic skeleton (6/6/6/5), while rhizopycnin B (4) was the first amino group containing dibenzo-α-pyrone. Rhizopycnolides A (1) and B (2) are proposed to be biosynthesized from polyketide and tricarboxylic acid cycle pathways. The isolated compounds were tested for their antibacterial, antifungal, and cytotoxic activities. Among them, rhizopycnolide A (1), rhizopycnins C (5) and D (6), TMC-264 (8), penicilliumolide D (11), and alternariol (12) were active against the tested pathogenic bacteria Agrobacterium tumefaciens, Bacillus subtilis, Pseudomonas lachrymans, Ralstonia solanacearum, Staphylococcus hemolyticus, and Xanthomonas vesicatoria with MIC values in the range 25-100 µg/mL. Rhizopycnin D (6) and TMC-264 (8) strongly inhibited the spore germination of Magnaporthe oryzae with IC50 values of 9.9 and 12.0 µg/mL, respectively. TMC-264 (8) showed potent cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780) with IC50 values of 3.2-7.8 µM.

Enhanced production of botrallin and TMC-264 with in situ macroporous resin adsorption in mycelial liquid culture of the endophytic fungus Hyalodendriella sp. Ponipodef12.

Hyalodendriella sp. Ponipodef12, an endophytic fungus from the hybrid "Neva" of Populus deltoides × P. nigra, is a high producer of the bioactive dibenzo-α-pyrones botrallin and TMC-264. However, both the botrallin and TMC-264 produced by Hyalodendriella sp. Ponipodef12 were retained as both intracellular and extracellular products. The aim of this study was to evaluate an in situ macroporous resin adsorption for enhancement of botrallin and TMC-264 production in mycelial liquid culture of Hyalodendriella sp. Ponipodef12. Production of botrallin and TMC-264 was most effectively enhanced by macroporous resin DM-301 among the thirteen nonionic macroporous resins tested. The highest botrallin yield (51.47 mg/L, which was 2.29-fold higher than the control at 22.49 mg/L) was obtained by adding resin DM-301 at 4.38% (g/mL) to the culture broth on day 24 and allowing a period of 4 days for adsorption. The highest TMC-264 yield reached 47.74 mg/L, which was 11.76-fold higher than that of the control (4.06 mg/L), and was achieved by adding DM-301 resin at 4.38% (w/v) in the culture broth on day 24 and allowing a period of 6 days for adsorption. The results show that in situ resin adsorption is an effective strategy for enhancing production of botrallin and TMC-264, and also for facilitating their recovery from mycelial liquid culture of Hyalodendriella sp. Ponipodef12.