Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.

Current therapies for Alzheimer's disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed.

Highly oxygenated germacrane-type sesquiterpenoids from the whole plant of Salvia cavaleriei H.Lév. and their biological activities.

The entire plant Salvia cavaleriei H.Lév. (Lamiaceae) is used as a traditional Chinese herbal medicine. Its leaves are edible, and the flowers can be soaked in water to make a health-care tea. In an effort to find natural bioactive chemical components, twelve undescribed germacrane-type sesquiterpenoids, salcavalins A-L, were isolated from the whole plant of S. cavaleriei and were identified as analogs. This is the first study to isolate highly oxygenated germacrane-type sesquiterpenoids from this plant. The structures of these undescribed compounds were elucidated by various spectroscopic methods, and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation and electronic circular dichroism calculations. The biological activity of these undescribed compounds on the production of tumor necrosis factor-alpha in lipopolysaccharide induced NR8383 cells was evaluated, and salcavalins I and K showed anti-inflammatory activity to some extent. Salcavalins A-C, F and L were found to be neuroprotective with antiparkinsonic potential in a nematode (Caenorhabditis elegans) model. In addition, salcavalins F and I displayed marked phytotoxic activity against radish seeds at a low concentration of 50 ppm. Our findings provide scientific justification to show that bioactive sesquiterpenoids from the edible herb have anti-inflammatory in vitro, neuroprotective and phytotoxic activities.

The relationship among knowledge, attitude, and behavior of workers on food safety in Taiwan's Company A.

In recent years, consumer awareness of food safety has been increasing, and food workers with professional food safety knowledge, attitude, and practical implementation are essential for maintaining the quality of food as well as preventing foodborne diseases. This study evaluates the knowledge, attitude, and implementation of food safety practices among employees in a food company in Taiwan. The employees were both who had received food safety knowledge and training and had yet to receive it. Data collection was carried out through 68 questionnaires, and analysis methods, including descriptive statistical analysis and multiple regression analysis, have performed. Before the first stage of education and training, 100% of the employees knew that food factories must conduct regular water quality testing. Still, the error rate for personal hygiene and safety was the highest. The second part has the highest average food safety attitude and the concept of food preservation. The third part of personnel behavior was to avoid cross-contamination. After the second stage of education and training of personnel in food safety knowledge, the attitude and behavior have been greatly improved. The findings of this study can be used as a reference for food suppliers to develop employee education and training.

The complete mitochondrial genome of Picromerus lewisi Scott 1874 (Hemiptera: Pentatomidae: Asopinae).

Picromerus lewisi Scott (Hemiptera: Pentatomidae) is a widely used natural enemy, through this study, we proved that its complete mitochondrial genome of it had similar characteristics to those of other Hemiptera. The mitogenome of P. lewisi is a circular molecule of 18,123 bp with 74.0% A + T content, containing 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and one control region. Phylogenetic tree based on 13 PCGs from 17 Panheteroptera species (two species of the Cimicomorpha are used as outgroup, 15 species belong to the Pentatomomorpha) suggested that P. lewisi has a closer relationship with E. thomsoni within Pentatomidae family.

Bioactive diterpenoids and sesquiterpenoids with different skeletons from Salvia digitaloides Diels.

Salvia has been regarded as a beneficial healing herb in ancient Egypt, Rome and Greece, and is listed as an official medicine in the pharmacopoeias of many countries worldwide. Currently, Salvia is widely used to flavor and preserve food. Here, two undescribed norabietane-type diterpenoids, sadigitaloides A and B, two undescribed germacrane-type sesquiterpenoids, sadigitaloides C and D, five undescribed guaiane-type sesquiterpenoid lactones, sadigitaloides E-I, two undescribed noreudesmane-type sesquiterpenoids, sadigitaloides J and K, one known diterpenoid, three known sesquiterpenoids, and three other types of known compounds were isolated from the 95% ethanol extract of the whole plants of Salvia digitaloides. Their structures and absolute configurations were characterized using 1D and 2D NMR spectroscopic techniques, electronic circular dichroism (ECD) calculations, HRESIMS experiments, and single-crystal X-ray diffraction analysis. Some compounds were evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced TNF-α production in rat macrophage NR8383 cells. Sadigitaloide A showed noticeable anti-inflammatory activity at a concentration of 100.0 µM. At a concentration of 60 µM, sadigitaloide B exhibited better protection of dopaminergic neurons than the positive control n-butylidenephthalide in the Caenorhabditis elegans model injured by 6-OHDA. The phytotoxic activities of some compounds were attributed to considerable inhibitory effects on the growth of the roots and hypocotyls of Raphanus sativus L seedlings, especially cis, trans-abscisic acid, whose inhibition rates were much higher than those of glyphosate at concentrations ranging from 50 to 400 ppm. These results indicated that abietane-type diterpenoids possessed excellent anti-inflammatory and neuroprotective activities and further suggested that the low-molecular-weight compounds exhibited outstanding phytotoxic activities.

Cryptotanshinone Alleviates Oxidative Stress and Reduces the Level of Abnormally Aggregated Protein in Caenorhabditis elegans AD Models.

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

Caesalpinbondin A, a Novel Diterpenoid Lactone With an Unprecedented Carbon Skeleton from the Seeds of Caesalpinia bonduc.

One novel diterpenoid lactone named caesalpinbondin A (1) that possesses an unprecedented tetracyclic ring system in which a 6/6/5-fused tricyclic ring and a 4,5-dimethyldihydrofuran-2(3H)-one were connected by a C-C single bond comprising a 5-(naphtho [2,3-b]furan-7-yl)dihydrofuran-2(3H)-one moiety was isolated from the seeds of Caesalpinia bonduc. Its chemical structure was established by extensive spectroscopic methods, and its absolute configuration was further determined by single-crystal X-ray diffraction analysis and electronic circular dichroism calculation. The biological evaluation suggested that compound 1 demonstrated potent anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A possible biogenetic pathway of 1 was also proposed.

Diterpenoids with α-glucosidase inhibitory activities from the fruits of Vitex trifolia Linn.

Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.

Nanoparticles-based anti-aging treatment of Alzheimer's disease.

Age is the strongest risk factor for Alzheimer's disease (AD). In recent years, the relationship between aging and AD has been widely studied, with anti-aging therapeutics as the treatment for AD being one of the mainstream research directions. Therapeutics targeting senescent cells have shown improvement in AD symptoms and cerebral pathological changes, suggesting that anti-aging strategies may be a promising alternative for AD treatment. Nanoparticles represent an excellent approach for efficiently crossing the blood-brain barrier (BBB) to achieve better curative function and fewer side effects. Thereby, nanoparticles-based anti-aging treatment may exert potent anti-AD therapeutic efficacy. This review discusses the relationship between aging and AD and the application and prospect of anti-aging strategies and nanoparticle-based therapeutics in treating AD.

Diterpenoid Caesalmin C Delays Aß-Induced Paralysis Symptoms via the DAF-16 Pathway in Caenorhabditis elegans.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aß-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aß-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aß monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.

Diterpenoids and C13 Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis.

Croton yanhuii (Family Euphorbiaceae) is an annual aromatic plant endemic to Yunnan Province, China, which yields an aromatic, spicy oil used as a flavoring and fragrance. The aim of the present study was to acquire secondary metabolites from the leaves and twigs of C. yanhuii and to evaluate their cytotoxic activity. Five new diterpenoids, croyanhuins A-E (1-5), and one new C13 nor-isoprenoid, croyanhuin F (6), were isolated from the leaves and twigs of C. yanhuii. Their structures and absolute configurations were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS) and confirmed by electronic circular dichroism (ECD) spectra or single-crystal X-ray diffraction analysis. Among the new terpenoids, compounds 1 and 3 inhibited cell proliferation and viability in a dose- and time-dependent manner, whereas both induced cleavage of either caspase-3 or PARP-1 in the SW480 cell line. Additionally, we observed that Z-YVAD-FMK and Z-VAD-FMK, two caspase inhibitors, inhibited the compound-dependent cell viability loss, suggesting that either of them can induce pyroptosis and caspase-dependent apoptosis. These biological assay results revealed that compounds 1 and 3 induce different kinds of programmed cell death in SW480 cells.

A new highly oxygenated germacranolide from Carpesium nepalense var. lanatum (C.B.Clarke) Kitam.

A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.

Transcriptomic analysis of gills in nitrite-tolerant and -sensitive families of Litopenaeus vannamei.

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimps still can withstand somewhat high concentrations of nitrite environment. However, few studies have been conducted about the tolerance molecular mechanism of Litopenaeus vannamei in the high concentration nitrite. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the L. vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO2, 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. During nitrite stress, energy metabolism in NT was significantly enhanced by activating the related genes expression of oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Meanwhile, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses also were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new insights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei.

2D van der Waals materials for ultrafast pulsed fiber lasers: review and prospect.

2D van der Waals materials are crystals composed of atomic layers, which have atomic thickness scale layers and rich distinct properties, including ultrafast optical response, surface effects, light-mater interaction, small size effects, quantum effects and macro quantum tunnel effects. With the exploration of saturable absorption characteristic of 2D van der Waals materials, a series of potential applications of 2D van der Waals materials as high threshold, broadband and fast response saturable absorbers (SAs) in ultrafast photonics have been proposed and confirmed. Herein, the photoelectric characteristics, nonlinear characteristic measurement technique of 2D van der Waals materials and the preparation technology of SAs are systematically described. Furthermore, the ultrafast pulsed fiber lasers based on classical 2D van der Waals materials including graphene, transition metal chalcogenides, topological insulators and black phosphorus have been fully summarized and analyzed. On this basis, opportunities and directions in this field, as well as the research results of ultrafast pulsed fiber lasers based on the latest 2D van der Waals materials (such as PbO, FePSe3, graphdiyne, bismuthene, Ag2S and MXene etc), are reviewed and summarized.

Polyoxygenated sesquiterpenoids from Salvia castanea and their potential anti-Alzheime's disease bioactivities.

Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500-3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1-6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1-6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1-9. The results showed the compounds 1-3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.

Cadinane-type sesquiterpenes from the resinous exudates of Commiphora myrrha and their anti-Alzheimer's disease bioactivities.

Commiphoins A-C (1-3), three new cadinane-type sesquiterpenes, together with two known cadinane-type sesquiterpenes (4 and 5) were isolated from the resinous exudates of Commiphora myrrha. Their structures and relative configurations were established on the basis of comprehensive spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses. Compounds 1 and 3-5 were screened for anti-Alzheimer's disease (AD) activities using the AD pathological model in Caenorhabditis elegans. The results showed that they all had significant anti-AD activities.

Integrated analysis of physiological, transcriptomic and metabolomic responses and tolerance mechanism of nitrite exposure in Litopenaeus vannamei.

Nitrite accumulation in aquatic environments is a potential risk factor that disrupts multiple physiological functions in aquatic animals. In this study, the physiology, transcriptome and metabolome of the control group (LV-C), nitrite-tolerance group (LV-NT) and nitrite-sensitive group (LV-NS) were investigated to identify the stress responses and mechanisms underlying the nitrite tolerance of Litopenaeus vannamei. After LV-NT and LV-NS were subjected to nitrite stress, the hemocyanin contents were significantly decreased, and hepatopancreas showed severe histological damage compared with LV-C. Likewise, the antioxidant enzymes were also significantly changed after nitrite exposure. The transcriptome data revealed differentially expressed genes associated with immune system, cytoskeleton remodeling and apoptosis in LV-NT and LV-NS. The combination of transcriptomic and metabolomic analysis revealed nitrite exposure disturbed metabolism processes in L. vannamei, including amino acid metabolism, nucleotide metabolism and lipid metabolism. The multiple comparative analysis implicated that higher nitrite tolerance of LV-NT than LV-NS may be attributed to enhanced hypoxia inducible factor-1α expression to regulate energy supply and gaseous exchange. Moreover, LV-NT showed higher antioxidative ability, detoxification gene expression and enhanced fatty acids contents after nitrite exposure in relative to LV-NS. Collectively, all these results will greatly provide new insights into the molecular mechanisms underlying the stress responses and tolerance of nitrite exposure in L. vannamei.

Relationship between ß-amyloid protein 1-42, thyroid hormone levels and the risk of cognitive impairment after ischemic stroke.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is not only a common consequence of stroke but also an important factor for adverse prognosis of patients. Biochemical indicators such as blood lipids and blood pressure are affected by many factors, and the ability of evaluating the progress of patients with PSCI is insufficient. Therefore, it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI. Recent studies have shown that ß-amyloid protein 1-42 (Aß1-42) and thyroid hormone levels are closely related to PSCI, which may be the influencing factors of PSCI, but there are few related studies. AIM: To investigate the relationship between serum levels of Aß and thyroid hormones in acute stage and PSCI and its predicted value. METHODS: A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study. Baseline data and serological indicators were recorded to assess cognitive function of patients. All patients were followed up for 1 year. Their cognitive functions were evaluated within 1 wk, 3 mo, 6 mo and 1 yr after stroke. At the end of follow-up, the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score, and the relationship between biochemical indexes and the progression of PSCI was explored. RESULTS: Compared with patients with non-PSCI, the levels of Aß1-42, triiodothyronine (T3) and free thyroxin were lower in the patients with PSCI. Repeated measures analysis of variance showed that the overall content of Aß1-42 and T3 in PSCI was also lower than that of the non-PSCI patients. Further analysis revealed that Aß1-42 (r = 0.348), T3 (r = 0.273) and free thyroxin (r = 0.214) were positively correlated with disease progression (P < 0.05), suggesting that these indicators have the potential to predict disease progression and outcome. Cox regression analysis showed that Aß1-42 and T3 were important factors of PSCI. Then stratified analysis showed that the lower the Aß1-42 and T3, the higher risk of PSCI in patients who were aged over 70, female and illiterate. CONCLUSION: Aß1-42 and T3 have the ability to predict the progression of PSCI, which is expected to be applied clinically to reduce the incidence of PSCI and improve the quality of life of patients.

Stress response and tolerance mechanisms of ammonia exposure based on transcriptomics and metabolomics in Litopenaeus vannamei.

Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.

[Removing Typical Odorants in Drinking Water by Vacuum Ultraviolet Combined with Chlorine].

For the effective removal of two typical odorants found in drinking water, 2-methylisoborneol (2-MIB) and geosmin (GSM), which cannot be effectively removed by the conventional water treatment processes, the advanced oxidation process of vacuum ultraviolet combined with chlorine (VUV/chlorine) was studied. The efficiency of this technology in the removal of these typical odorants was investigated; the effects of ultraviolet intensity, chlorine concentration, pH, bicarbonate concentration, and humic acid concentration on the degradation of these typical odorants were examined, and the role of hydroxyl radicals (·OH) in the degradation of these typical odorants was analyzed. The purge and trap method coupled with gas chromatography and mass spectrometry (GC/MS) was used to determine the concentrations of the typical odorants. The results showed that the VUV/chlorine technology removed typical odorants effectively, and the removal rates of 2-MIB and GSM increased by 15% and 8%, respectively, in 30 minutes, compared with that by the UV/chlorine technology. With the increase in chlorine concentration and ultraviolet intensity, the degradation rates of the typical odorants was accelerated. The removal of the typical odorants was obvious under weak acid condition, and the removal rates of 2-MIB and GSM reached 95% and 96%, respectively, in 10 minutes under the condition of pH 5. Bicarbonate and humic acid competed with free radicals in the reaction system to inhibit the degradation of the typical odorants. The removal rates of 2-MIB and GSM decreased appreciably by 40% and 31%, respectively, when 1 mmol·L-1tert-butanol was added to the reaction mixture, which indicated that hydroxyl radicals (·OH) played a major role in the removal of these typical odorants.