Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

Aim: The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. Methods: The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. Results: The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and ß-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3ß at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. Conclusions: The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Investigating the spatiotemporal expression of CBTS genes lead to the discovery of tobacco root as a cembranoid-producing organ.

Tobacco cembranoids, known for their anti-insect and antifungal properties, were shown to be mainly present on the surface of leaves and flowers, being biosynthesized by their trichomes. It remains unclear whether they could be biosynthesized in other organs without trichomes. Cembratrien-ol synthases (CBTSs) catalyze the conversion of GGPP to CBT-ols and thus play an important role in cembranoid biosynthesis. This study identified the CBTS family genes in tobacco and examined their spatiotemporal expression patterns. The CBTS genes showed diverse expression patterns in tobacco organs, with the majority highly expressed in leaves and a few highly expressed in flowers. The expression of CBTS genes were also correlated with the development of tobacco plants, and most of them showed the highest expression level at the budding stage. Furthermore, their expression is mediated by the JA (jasmonate) signaling in all tobacco organs. Several CBTS genes were found to be highly expressed in tobacco roots that have no trichomes, which prompted us to determine the cembranoid production in roots and other organs. GC-MS and UPLC assays revealed that cembranoids were produced in all tobacco organs, which was supported by the bioactivity assay results that almost all these CBTS enzymes could catalyze CBT-ol biosyntheis in yeast, and that the content ratio of CBT-ols and CBT-diols in tobacco roots was different to that in leaves. This work sheds insights into the expression profiles of tobacco CBTS genes and provides a feasibility to engineer tobacco roots for industrial production of cembranoids.

Correction: Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer's Disease in APP+PS1 Mice.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

Soil amendments alter cadmium distribution and bacterial community structure in paddy soils.

Soil amendments play a pivotal role in ensuring the safety of food production by inhibiting the transfer of heavy metal ions from soils to crops. Nevertheless, their impact on soil characteristics and the microbial community and their role in reducing cadmium (Cd) accumulation in rice remain unclear. In this study, pot experiments were conducted to investigate the effects of three soil amendments (mineral, organic, and microbial) on the distribution of Cd speciation, organic components, iron oxides, and microbial community structure. The application of soil amendments resulted in significant reductions in the soil available Cd content (16 %-51 %) and brown rice Cd content (16 %-78 %), facilitating the transformation of Cd from unstable forms (decreasing 10 %-20 %) to stable forms (increasing 77 %-150 %) in the soil. The mineral and organic amendments increased the soil cation exchange capacity (CEC) and plant-derived organic carbon (OC), respectively, leading to reduced Cd accumulation in brown rice, while the microbial amendment enhanced OC complexity and the abundances of Firmicutes and Bacteroidota, contributing to the decreased rice Cd uptake. The synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy indicated that soil amendments regulated soil Cd species by promoting iron oxides and OC coupling. Moreover, both organic and microbial amendments significantly reduced the diversity and richness of the bacterial communities and altered their compositions and structures, by increasing the relative abundances of Bacteroidota and Firmicutes and decreasing those of Acidobacteria, Actinobacteria, and Myxococcota. Soil microbiome analysis revealed that the increase of Firmicutes and Bacteroidota associated with Cd adsorption and sequestration contributed to the suppression of soil Cd reactivity. These findings offer valuable insights into the potential mechanisms by which soil amendments regulate the speciation and bioavailability of Cd, and improve the bacterial communities, thereby providing guidance for agricultural management practices.

Meta-analysis on the impact of immune senescence: Unravelling the interplay in cutaneous wound healing and lung cancer progression.

The primary objective of this meta-analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non-small-cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta-analysis guarantee thorough and ethically sound methodology for amalgamating pre-existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes.

BACKGROUND: The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. AIM: To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. METHODS: We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. RESULTS: There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (ß = 1.953, P = 0.005). CONCLUSION: High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.

Research progress of nano-scale secondary ion mass spectrometry (NanoSIMS) in soil science: Evolution, applications, and challenges.

Nano-scale secondary ion mass spectrometry (NanoSIMS) has emerged as a powerful analytical tool for investigating various aspects of soils. In recent decades, the widespread adoption of advanced instrumentation and methods has contributed significantly to our understanding of organic-mineral assemblages. However, few literature reviews have comprehensively summarized NanoSIMS and its evolution, applications, limitations, and integration with other analytical techniques. In this review, we addressed this gap by comprehensively overviewing the development of NanoSIMS as an analytical tool in soils. This review covers studies on soil organic matter (SOM) cycling, soil-root interactions, and the behavior of metals, discussing the capability and limitations related to the distribution, composition, and interactions of various soil components that occur at mineral-organic interfaces. Furthermore, we examine recent advancements in high-resolution imaging and mass spectrometry technologies and their impact on the utilization of NanoSIMS in soils, along with potential new applications such as utilizing multiple ion beams and integrating them with other analytical techniques. The review emphasizes the importance of employing advanced techniques and methods to explore micro-interfaces and provide in situ descriptions of organic-mineral assemblages in future research. The ongoing development and refinement of NanoSIMS may yield new insights and breakthroughs in soil science, deepening our understanding of the intricate relationships between soil components and the processes that govern soil health and fertility.

Ultralow Power and Shifting-Discretized Magnetic Racetrack Memory Device Driven by Chirality Switching and Spin Current.

Magnetic racetrack memory has significantly evolved and developed since its first experimental verification and is considered one of the most promising candidates for future high-density on-chip solid-state memory. However, both the lack of a fast and precise magnetic domain wall (DW) shifting mechanism and the required extremely high DW motion (DWM) driving current make the racetrack difficult to commercialize. Here, we propose a method for coherent DWM that is free from the above issues, which is driven by chirality switching (CS) and an ultralow spin-orbit-torque (SOT) current. The CS, as the driving force of DWM, is achieved by the sign change of the Dzyaloshinskii-Moriya interaction, which is further induced by a ferroelectric switching voltage. The SOT is used to break the symmetry when the magnetic moment is rotated in the Bloch direction. We numerically investigate the underlying principle and the effect of key parameters on the DWM by micromagnetic simulations. Under the CS mechanism, a fast (∼102 m/s), ultralow energy (∼5 attoJoule), and precisely discretized DWM can be achieved. Considering that skyrmions with topological protection and smaller size are also promising for future racetracks, we similarly evaluate the feasibility of applying such a CS mechanism to a skyrmion. However, we find that the CS causes it to "breathe" instead of moving. Our results demonstrate that the CS strategy is suitable for future DW racetrack memory with ultralow power consumption and discretized DWM.

Multi-Targeting Intranasal Nanoformulation as a Therapeutic for Alzheimer's Disease.

Melatonin, insulin, and Δ9-tetrahydrocannabinol (THC) have been shown to reverse cognitive deficits and attenuate neuropathologies in transgenic mouse models of Alzheimer's disease (AD) when used individually. Here, we evaluated the therapeutic properties of long-term intranasal treatment with a novel nanoformulation containing melatonin, insulin, and THC in aged APPswe/PS1ΔE9 (APP/PS1) mice, a transgenic model of AD. Transgenic mice at the age of 12 months were intranasally administered with a new nanoformulation containing melatonin, insulin, and THC at doses of 0.04, 0.008, and 0.02 mg/kg, respectively, once daily for 3 months. The spatial memory of the mice was assessed using the radial arm water maze (RAWM) test before and after drug treatment. Brain tissues were collected at the end of the treatment period for the assessment of Aß load, tauopathy state, and markers of mitochondrial function. The RAWM test revealed that the treatment with the melatonin-insulin-THC (MIT) nasal spray improved the spatial learning memory of APP/PS1 mice significantly. Results of protein analyses of brain homogenates indicated that MIT treatment significantly decreased the tau phosphorylation implicated in tau toxicity (p < 0.05) and the expression of CKMT1 associated with mitochondrial dysfunction. Moreover, MIT significantly decreased the expression of two mitochondrial fusion-related proteins, Mfn2 and Opa1 (p < 0.01 for both), while increasing the expression of a mitophagy regulator, Parkin, suggesting a compensatory enhancement of mitophagy due to MIT-promoted mitochondrial fusion. In conclusion, this study was the first to demonstrate the ability of an MIT nanoformulation to improve spatial memory in AD mice through its multi-targeting effects on Aß production, tau phosphorylation, and mitochondrial dynamics. Thus, MIT may be a safe and effective therapeutic for AD.

Performance of constructed wetlands with different water level for treating graphene oxide wastewater: Characteristics of plants and microorganisms.

Constructed wetlands (CWs) have been expected advantages in emerging pollutant removal, but with less known on their characteristic when treating wastewater containing graphene oxide (GO). In present study, we investigated characteristics of Iris pseudacorus, microorganisms, and pollutant removal in CWs with 60 cm and 37 cm water level (termed HCW and LCW). Plants in LCW had higher chlorophyll content and lower activities of antioxidant enzyme (superoxide dismutase, catalase, peroxidase) as well as malondialdehyde content. Substrate enzyme activities were affected by time and CW type. LCW increased only dehydrogenase activities, while HCW increased catalase, urease, neutral phosphatase, and arylsulfatase activities. Sequencing analysis revealed that microbial community showed higher richness and diversity in LCW, but this dissimilarity could be eased by time-effect. Proteobacteria (25.62-60.36%) and Actinobacteria (13.86-56.20%) were stable dominant phyla in CWs. Ratio of Proteobacteria/Acidobacteria indicated that trophic status of plant rhizosphere zone was lower in LCW. Nitrospirae were enriched to 0.16-0.68% and 0.75-1.42% in HCW and LCW. The enrichment of phyla Proteobacteria and Firmicutes in HCW was attributed to class Gammaproteobacteria and genus Enterococcus. GO transformation showed some reductions in CWs, which could be affected by water depth and substrate depth. Overall, HCW achieved nitrogen and phosphorus removal for 48.78-62.99% and 95.01%, which decreased by 8.41% and 7.31% in LCW. COD removal was less affected reaching 93%. This study could provide some new evidence for CWs to treat wastewater containing GO.

Large tunneling magnetoresistance in van der Waals magnetic tunnel junctions based on FeCl2 films with interlayer antiferromagnetic couplings.

Antiferromagnets (AFMs) are some of the most promising candidates for next-generation magnetic memory technology owing to their advantages over conventional ferromagnets (FMs), such as zero stray field and THz-range magnetic resonance frequency. Motivated by the recent synthesis of FeCl2 films with interlayer AFM and intralayer FM couplings, we investigated the magnetic properties of few-layer FeCl2 and the spin-dependent transmissions of graphite/bilayer FeCl2/graphite and Au/n-layer FeCl2/Au magnetic tunnel junctions (MTJs) using first-principles calculations combined with the nonequilibrium Green's function. The interlayer AFM coupling of FeCl2 is certified to be stable and independent of the stacking orders and relative displacement between layers. Furthermore, based on the Au electrode with better conductive performance than the graphite electrode and monolayer 1T-FeCl2 with complete spin polarization, high Curie temperature and large magnetic anisotropic energy, a high tunnel magnetoresistance (TMR) ratio of 2.7 × 103% is achieved in Au/bilayer FeCl2/Au MTJs at zero bias and it increases with different layers of FeCl2 (n = 2-10). These excellent spin transport properties of Au/n-layer FeCl2/Au MTJs based on two-dimensional (2D) AFM barriers with out-of-plane magnetization directions suggest their great potential for application in high-reliability, high-speed and high-density spintronic devices.

Transcranial Electromagnetic Treatment Stops Alzheimer's Disease Cognitive Decline over a 2½-Year Period: A Pilot Study.

Background: There is currently no therapeutic that can stop or reverse the progressive memory impairment of Alzheimer's disease (AD). However, we recently published that 2 months of daily, in-home transcranial electromagnetic treatment (TEMT) reversed the cognitive impairment in eight mild/moderate AD subjects. These cognitive enhancements were accompanied by predicted changes in AD markers within both the blood and cerebrospinal fluid (CSF). Methods: In view of these encouraging findings, the initial clinical study was extended twice to encompass a period of 2½ years. The present study reports on the resulting long-term safety, cognitive assessments, and AD marker evaluations from the five subjects who received long-term treatment. Results: TEMT administration was completely safe over the 2½-year period, with no deleterious side effects. In six cognitive/functional tasks (including the ADAS-cog13, Rey AVLT, MMSE, and ADL), no decline in any measure occurred over this 2½-year period. Long-term TEMT induced reductions in the CSF levels of C-reactive protein, p-tau217, Aß1-40, and Aß1-42 while modulating CSF oligomeric Aß levels. In the plasma, long-term TEMT modulated/rebalanced levels of both p-tau217 and total tau. Conclusions: Although only a limited number of AD patients were involved in this study, the results suggest that TEMT can stop the cognitive decline of AD over a period of at least 2½ years and can do so with no safety issues.

Iris pseudacorus as precursor affecting ecological transformation of graphene oxide and performance of constructed wetland.

The role of plants is largely unknown in constructed wetlands (CWs) exposed to phytotoxic nanomaterials. Present study investigated transformation of graphene oxide (GO) and performance of CWs with Iris pseudacorus as precursor. GO was trapped by CWs without dependence on plants. GO could move to lower substrate layer and present increases on defects/disorders with stronger effects in planted CW. Before adding GO, planted CW achieved better removal both of phosphorus and nitrogen. After adding GO, phosphorus removal in planted CW was 93.23-95.71% higher than 82.55-90.07% in unplanted CW. However, total nitrogen removal was not improved, showing 48.20-56.66% and 53.44-56.04% in planted and unplanted CWs. Plant improved urease, phosphatase, and arylsulfatase, but it decreased ß-glucosidase and had less effects on dehydrogenase and catalase. Pearson correlation matrix revealed that plant enhanced microbial interaction with high degree of positive correlation. Moreover, there were obvious shifts in microbial community at phylum and genus level, which presented closely positive action on substrate enzyme activities. The functional profile was less affected due to functional redundancy in microbial system, but time effects were obvious in CWs, especially in planted CW. These findings could provide the basis on understanding role of plants in CWs for treating nanoparticles wastewater.

Transcranial Electromagnetic Treatment "Rebalances" Blood and Brain Cytokine Levels in Alzheimer's Patients: A New Mechanism for Reversal of Their Cognitive Impairment.

Background: The immune system plays a critical role in the development and progression of Alzheimer's disease (AD). However, there is disagreement as to whether development/progression of AD involves an over-activation or an under-activation of the immune system. In either scenario, the immune system's cytokine levels are abnormal in AD and in need of rebalancing. We have recently published a pilot clinical trial (https://clinicaltrials.gov/ct2/show/NCT02958930) showing that 2 months of daily in-home Transcranial Electromagnetic Treatment (TEMT) was completely safe and resulted in reversal of AD cognitive impairment. Methods: For the eight mild/moderate AD subjects in this published work, the present study sought to determine if their TEMT administration had immunologic effects on blood or CSF levels of 12 cytokines. Subjects were given daily in-home TEMT for 2 months by their caregivers, utilizing first-in-class MemorEM™ devices. Results: For eight plasma cytokines, AD subjects with lower baseline cytokine levels always showed increases in those cytokines after both a single treatment or after 2-months of daily TEMT. By contrast, those AD subjects with higher baseline cytokine levels in plasma showed treatment-induced decreases in plasma cytokines at both time points. Thus, a gravitation to reported normal plasma cytokine levels (i.e., a "rebalancing") occurred with both acute and long-term TEMT. In the CSF, TEMT-induced a similar rebalancing for seven measurable cytokines, the direction and extent of changes in individual subjects also being linked to their baseline CSF levels. Conclusion: Our results strongly suggest that daily TEMT to AD subjects for 2-months can "rebalance" levels for 11 of 12 cytokines in blood and/or brain, which is associated with reversal of their cognitive impairment. TEMT is likely to be providing these immunoregulatory effects by affecting cytokine secretion from: (1) blood cells traveling through the head's vasculature, and (2) the brain's microglia/astrocytes, choroid plexus, or neurons. This rebalancing of so many cytokines, and in both brain and systemic compartments, appears to be a remarkable new mechanism of TEMT action that may contribute substantially to it's potential to prevent, stop, or reverse AD and other diseases of aging.

The Memory Benefit to Aged APP/PS1 Mice from Long-Term Intranasal Treatment of Low-Dose THC.

THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery. Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group. An enzyme-linked immunosorbent assay showed that the Aß1-40 and 1-42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment. Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer's disease-related cognitive performance.

The efficacy and safety of combined traditional Chinese and western medicine in the treatment of chronic obstructive pulmonary disease complicated with respiratory failure: a systematic review and meta-analysis study.

BACKGROUND: The conventional drugs to treat chronic obstructive pulmonary disease (COPD) complicated with respiratory failure (RF) (COPD + RF) in western medicine include antibiotics, etc., but the patients have serious adverse reactions and are prone to drug resistance. This study aims to analyze the curative effect of traditional Chinese medicine (TCM) combined with Western medicine (WM) in treating COPD + RF. METHODS: Randomized controlled studies on the treatment of COPD with RF were searched in PubMed, Web of Science, Embase, and The Cochrane Library. Outcome measures were treatment efficiency, oxygen partial pressure (PO2), partial pressure of carbon dioxide (PCO2), and pulmonary function [forced expiratory volume in 1 second (FEV1)%]. The Cochrane Reviewer's Handbook 4.2.5 was adopted for quality assessment of studies, and the data was analyzed using RevMan 5.3. RESULTS: Seven suitable articles were selected, including 490 patients. The literature quality met the requirements of this article, and there was no obvious publication bias. The effective rate of patients in the combined TCM and WM treatment group and control group (WM treatment) was analyzed as odds ratio (OR) [95% confidence interval (CI): 5.40 (3.14 to 9.29)], and statistically tested as Z=6.09 (P<0.00001). The analysis structure of PO2 after treatment was mean difference (MD) (95% CI): 5.92 (2.27 to 9.56), and the statistical analysis suggested Z=3.18, P=0.001. The analysis of PCO2 after treatment was MD (95% CI): -4.53 (-7.14 to -1.92), and Z=3.40, P=0.0007. The analysis structure of lung function index data was MD (95% CI): 8.16 (2.57 to 13.75), and Z=2.86 (P=0.004). DISCUSSION: The TCM combined with WM can effectively treat the symptoms related to COPD; the treatment efficiency is significantly improved compared with traditional WM; and the PO2, PCO2, and lung function (FEV1%) are improved for sure after treatment. Data of this study show that the combined treatment of TCM and WM has a good therapeutic effect on the acute exacerbation of COPD complicated with RF, which is worthy of clinical application. However, the included outcome indexes in this study were not sufficient, and the sample size and outcome indexes should be further expanded in the future.

Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice.

Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer's disease (AD) have been sparse due to the concern about THC's psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-ß (Aß) production was examined in N2a/AßPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months. The in vitro study showed that THC inhibited Aß aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aß oligomers, phospho-tau and total tau, and increased the expression of Aß monomers and phospho-GSK-3ß (Ser9) in the THC-treated brain tissues. In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.

Developing an Effective Peptide-Based Vaccine for COVID-19: Preliminary Studies in Mice Models.

Coronavirus disease 2019 (COVID-19) has caused massive health and economic disasters worldwide. Although several vaccines have effectively slowed the spread of the virus, their long-term protection and effectiveness against viral variants are still uncertain. To address these potential shortcomings, this study proposes a peptide-based vaccine to prevent COVID-19. A total of 15 B cell epitopes of the wild-type severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein were selected, and their HLA affinities predicted in silico. Peptides were divided into two groups and tested in C57BL/6 mice with either QS21 or Al(OH)3 as the adjuvant. Our results demonstrated that the peptide-based vaccine stimulated high and durable antibody responses in mice, with the T and B cell responses differing based on the type of adjuvant employed. Using epitope mapping, we showed that our peptide-based vaccine produced antibody patterns similar to those in COVID-19 convalescent individuals. Moreover, plasma from vaccinated mice and recovered COVID-19 humans had the same neutralizing activity when tested with a pseudo particle assay. Our data indicate that this adjuvant peptide-based vaccine can generate sustainable and effective B and T cell responses. Thus, we believe that our peptide-based vaccine can be a safe and effective vaccine against COVID-19, particularly because of the flexibility of including new peptides to prevent emerging SARS-CoV-2 variants and avoiding unwanted autoimmune responses.

Comprehensive characterization of the bacterial community structure and metabolite composition of food waste fermentation products via microbiome and metabolome analyses.

Few studies have characterized the microbial community and metabolite profile of solid food waste fermented products from centralized treatment facilities, which could potentially be processed into safe animal feeds. In this study, 16S rRNA gene sequencing and liquid/gas chromatography-mass spectrometry were conducted to investigate the bacterial community structure and metabolite profile of food waste samples inoculated with or without 0.18% of a commercial bacterial agent consisting of multiple unknown strains and 2% of a laboratory-made bacterial agent consisting of Enterococcus faecalis, Bacillus subtilis and Candida utilis. Our findings indicated that microbial inoculation increased the crude protein content of food waste while reducing the pH value, increasing lactic acid production, and enhancing aerobic stability. Microbial inoculation affected the community richness, community diversity, and the microbiota structure (the genera with abundances above 1.5% in the fermentation products included Lactobacillus (82.28%) and Leuconostoc (1.88%) in the uninoculated group, Lactobacillus (91.85%) and Acetobacter (2.01%) in the group inoculated with commercial bacterial agents, and Lactobacillus (37.11%) and Enterococcus (53.81%) in the group inoculated with homemade laboratory agents). Microbial inoculation reduced the abundance of potentially pathogenic bacteria. In the metabolome, a total of 929 substances were detected, 853 by LC-MS and 76 by GC-MS. Our results indicated that inoculation increased the abundance of many beneficial metabolites and aroma-conferring substances but also increased the abundance of undesirable odors and some harmful compounds such as phenol. Correlation analyses suggested that Leuconostoc, Lactococcus, and Weissella would be promising candidates to improve the quality of fermentation products. Taken together, these results indicated that inoculation could improve food waste quality to some extent; however, additional studies are required to optimize the selection of inoculation agents.

Molecular evolution and functional characterization of chitinase gene family in Populus trichocarpa.

Chitinases, the chitin-degrading enzymes, have been shown to play important role in defense against the chitin-containing fungal pathogens. In this study, we identified 48 chitinase-coding genes from the woody model plant Populus trichocarpa. Based on phylogenetic analysis, the Populus chitinases were classified into seven groups. Different gene structures and protein domain architectures were found among the seven Populus chitinase groups. Selection pressure analysis indicated that all the seven groups are under purifying selection. Phylogenetic analysis combined with chromosome location analysis showed that Populus chitinase gene family mainly expanded through tandem duplication. The Populus chitinase gene family underwent marked expression divergence and is inducibly expressed in response to treatments, such as chitosan, chitin, salicylic acid and methyl jasmonate. Protein enzymatic activity analysis showed that Populus chitinases had activity towards both chitin and chitosan. By integrating sequence characteristic, phylogenetic, selection pressure, gene expression and protein activity analysis, this study shed light on the evolution and function of chitinase family in poplar.