N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine.

Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Previously, we reported that α-syn clusters synaptic vesicles (SV) 1, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering 2. Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological condition and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn's N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes α-syn-LPC interaction for mediating α-syn's function in SV clustering.

A review of natural products targeting tumor immune microenvironments for the treatment of lung cancer.

Lung cancer (LC) produces some of the most malignant tumors in the world, with high morbidity and mortality. Tumor immune microenvironment (TIME), a component of the tumor microenvironment (TME), are critical in tumor development, immune escape, and drug resistance. The TIME is composed of various immune cells, immune cytokines, etc, which are important biological characteristics and determinants of tumor progression and outcomes. In this paper, we reviewed the recently published literature and discussed the potential uses of natural products in regulating TIME. We observed that a total of 37 natural compounds have been reported to exert anti-cancer effects by targeting the TIME. In different classes of natural products, terpenoids are the most frequently mentioned compounds. TAMs are one of the most investigated immune cells about therapies with natural products in TIME, with 9 natural products acting through it. 17 natural products exhibit anti-cancer properties in LC by modulating PD-1 and PD-L1 protein activity. These natural products have been extensively evaluated in animal and cellular LC models, but their clinical trials in LC patients are lacking. Based on the current review, we have revealed that the mechanisms of LC can be treated with natural products through TIME intervention, resulting in a new perspective and potential therapeutic drugs.

Effect of graphene oxide on sodium alginate hydrogel as a carrier triggering release of ibuprofen.

The design and preparation of safe wound dressings with antibacterial and controlled drug release abilities is valuable in medicine. This research focuses on the fabrication of a hydrogel carrier with graphene oxide (GO)-triggered ibuprofen (IBU) release to control inflammation. The hydrogel was prepared by cross-linking the base polymer sodium alginate (SA) and functionalized GO. The morphology of the gel was observed by a scanning electron microscope (SEM), and its structure was analyzed through X-ray diffraction (XRD) and Fourier transform infrared reflection (FTIR) spectroscopy. The effects of GO on swelling capacity, IBU release behavior and antibacterial activity were investigated by using the prepared GO/SA hydrogel as a drug carrier and IBU as a drug model. In vitro studies confirmed that the GO/SA hydrogel had good antimicrobial activity and excellent cytotoxicity. The analysis of cumulative IBU release rates revealed that the addition of GO could promote the release of IBU, and the change in GO content did not have a prominent effect on IBU release. At the same time, the rate of IBU release from the GO/SA hydrogel was affected by near-infrared light. Under a light source, the release rate of IBU increased, and the release amount of IBU showed a clear stepwise increase under light on-off conditions. These results suggest that the GO/SA hydrogel could be a potential antibacterial and anti-inflammatory wound dressing.

Comparative Toxicological Effects of Perfluorooctane Sulfonate and Its Alternative 6:2 Chlorinated Polyfluorinated Ether Sulfonate on Earthworms.

High levels of 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), which is a substitute for perfluorooctane sulfonate (PFOS), are detected in various environmental matrices, wildlife, and humans. Chlorinated polyfluorinated ether sulfonate has received increased attention due to its potential risk to ecosystems. However, its toxicity in the soil organisms remains unclear. In the present study, a comparative investigation was conducted on the toxicities of 6:2 Chlorinated polyfluorinated ether sulfonate (F-53B) and PFOS to the earthworm Eisenia. fetida. F-53B was significantly more acutely toxic to earthworms than PFOS, with median lethal concentrations of 1.43 and 1.83 mmol/kg dry soil (~816 and 984 mg/kg dry soil), respectively. Although both F-53B and PFOS, at 0.4 mmol/kg dry soil (=228 and 215 mg/kg dry soil) caused oxidative stress in earthworms, as evidenced by increased superoxide dismutase, peroxidase, and catalase activities as well as malondialdehyde level, the stress caused by F-53B was higher than that caused by PFOS. In transcriptomic and metabolomic studies, negative effects of PFOS and F-53B were observed on several metabolic processes in earthworms, including protein digestion and amino acid absorption, lipid metabolism, and the immune response. Compared with PFOS, F-53B exhibited a weaker disruption of lipid metabolism, comparable potency for toxicity to the immune response, and a stronger potency in extracellular matrix destruction along with apoptosis and ferroptosis induction. Hence, our data suggest that F-53B is more toxic than PFOS to earthworms. The findings provide some new insights into the potential toxicity of F-53B to soil organisms. Environ Toxicol Chem 2024;43:170-181. © 2023 SETAC.

[Research status of insect infestation of Chinese medicinal materials during storage].

During the storage process, Chinese medicinal materials are susceptible to insect infestation due to their own nature and external storage factors. Infestation by insects can have varying impacts on the materials. In mild cases, it affects the appearance and reduces consumer purchasing power, while in severe cases, it affects the quality, reduces medicinal value, and introduces impurities such as insect bodies, excrement, and secretions, resulting in significant contamination of the medicinal materials. This study reviewed the rele-vant factors influencing insect infestation in Chinese medicinal materials and the compositional changes that occur after infestation and summarized maintenance measures for preventing insect infestation. Additionally, it provided an overview of detection techniques applicable to identifying insect infestation during the storage of Chinese medicinal materials. During the storage process, insect infestation is the result of the combined effects of biological factors(source, species, and population density of insects), intrinsic factors(moisture, chemical composition, and metabolism), and environmental factors(temperature, relative humidity, and oxygen content). After infestation, there are significant changes in the content of constituents in the medicinal materials. By implementing strict pre-storage inspections, regular maintenance after storage, and appropriate storage and maintenance methods, the occurrence of insect infestation can be reduced, and the preservation rate of Chinese medicinal materials can be improved. The storage and maintenance of Chinese medicinal materials are critical for ensuring their quality. Through scientifically standardized storage and strict adherence to operational management standards, the risk of insect infestation can be minimized, thus guaranteeing the quality of Chinese medicinal materials.

Comprehensive metabolomic variations of hawthorn before and after insect infestation based on the combination analysis of 1H NMR and UPLC-MS.

Hawthorn, the sliced and dried ripe fruits of Crataegus pinnatifida Bge. Var. Major N. E. Br. (Rosaceae), is an edible and medicinal substance with a variety of health-promoting benefits. Hawthorn needs to be stored in warehouses after harvesting to meet people's perennial demand. However, it is easily infested by insects of Plodia interpunctella and Tribolium castaneum during storage, which inevitably leads to poor quality and causes adverse effects on people's health. So far, there has been no report on insect-infested hawthorn. In this study, we analyzed the changes of metabolites in hawthorn before and after insect infestation and screened out potential biomarkers to effectively and quickly detect the occurrence of insect infestation. A combination analysis of 1H nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to identify the primary and secondary metabolites. By the comparison of hawthorn and insect-infested hawthorn samples, it was found that the differences were mainly manifested in the content of metabolites. The metabolites of 32 and 1463 were identified by 1H NMR and UPLC-MS analysis, respectively. According to the parameters of VIP >1 and P < 0.05, 10 differential metabolites were screened from 1H NMR analysis. Based on the parameters of VIP >1.0, P < 0.05, and (FC) > 1 or < 1, 47 differential metabolites were screened from UPLC-MS analysis. Therefore, a total of 57 differential metabolites were considered as differential biomarkers. The heat map analysis showed that the content of some differential biomarkers with significant pharmacological activities decreased after insect infestation. Through receiver operating characteristic (ROC) curve assessment, 52 differential biomarkers (6 of 1H NMR analysis and 46 of UPLC-MS analysis) were screened to distinguish whether insect infestation occurred in hawthorn. This is the first report on the changes of metabolites between hawthorn and insect-infested hawthorn and on the screening of differential biomarkers for monitoring insects. These results contributed to evaluate quality of hawthorn and ensure food safety for consumers. It also laid a foundation for further research on the infestation mechanism and safe storage monitoring in hawthorn.

A Comprehensive Quality Analysis of Different Colors of Medicinal and Edible Honeysuckle.

Honeysuckle (the dried flower bud or opening flower of Lonicera japonica Thunb.), a medicinal and edible substance, has is greatly popular among consumers for its remarkable health effects, such as antioxidant, antibacterial, and anti-inflammatory effects. However, due to the influences of processing methods, storage conditions, and other factors, honeysuckles show different colors which can directly reflect the quality and the price on the market. In order to comprehensively compare the quality of different colors, 55 batches of honeysuckle samples were collected and analyzed. Their color parameters, chlorophyll content (chl), total phenol content (TPC), total flavonoid content (TFC), antioxidant activity (AA), main active compounds, and metabolites were measured. As a result, the initial green-white (GW) samples, a kind of highest-quality honeysuckle, had the smallest a* value, largest h*, chl, TPC, TFC, and AA values, and highest content of chlorogenic acid and cynaroside. There was a significant difference between GW samples and a series of discolored samples. As the color darkened or lightened, the quality gradually decreased. The yellow-brown (YB) samples were of the worst quality and were no longer available for clinical and health purposes. A series of differential metabolites, such as quercetin-7-O-glucoside and secologanoside, could be used as important references to evaluate the quality of differently colored samples. The metabolic profile of honeysuckle provided new insights into the process of color change and laid a foundation for further honeysuckle quality control. The correlation results showed that the a* and h* values significantly affect the abovementioned quality indicators and the 10 main active compounds. In other words, the color difference could directly reflect the quality and clinical efficacy. Multiple regression analysis was carried out using combined L*, a*, and b* values to predict the quality of honeysuckle. This is the first time the quality of different color honeysuckle samples on the post-harvest link has been systematically compared and a demonstration of medicinal and edible substances with different colors has been provided.

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation.

Osteoporosis (OP) is a metabolic disease that affects bone, resulting in a progressive decrease in bone mass, quality, and micro-architectural degeneration. Natural products have become popular for managing OP in recent years due to their minimal adverse side effects and suitability for prolonged use compared to chemically synthesized products. These natural products are known to modulate multiple OP-related gene expressions, making epigenetics an important tool for optimal therapeutic development. In this study, we investigated the role of epigenetics in OP and reviewed existing research on using natural products for OP management. Our analysis identified around twenty natural products involved in epigenetics-based OP modulation, and we discussed potential mechanisms. These findings highlight the clinical significance of natural products and their potential as novel anti-OP therapeutics.

Spatiotemporal optical properties of dissolved organic matter in a sluice-controlled coastal plain river with both salinity and trophic gradients.

Due to the combined effect of sluices and sea tide, the sluice-controlled coastal plain river would be characterized by both trophic state and salinity gradients, affecting the spatiotemporal optical properties of dissolved organic matter (DOM). In this study, we investigated the spatiotemporal variation of water quality parameters and optical properties of DOM in the Haihe River, a representative sluice-controlled coastal plain river in Tianjin, China. A significant salinity gradient and four trophic states were observed in the water body of the Haihe River. Two humic- and one protein-like substances were identified from the DOM by the three-dimensional fluorescence spectra combined with the parallel factor (PARAFAC) analysis. Pearson's correlation analysis and redundancy analysis (RDA) showed that the salinity significantly affected the abundance of chromophoric DOM (CDOM) but did not cause significant changes in the fluorescence optical characteristics. In addition, the effect of Trophic state index (TSI) on the CDOM abundance was greater than that on the fluorescence intensity of fluorescent dissolved organic matter (FDOM). In the water body with both salinity and trophic state gradients, TSI posed a greater influence than salinity on the CDOM abundance. Our results fill the research gap in spatiotemporal DOM characteristics and water quality variation in water bodies with both salinity and trophic state gradients. These results are beneficial for clarifying the joint influence of saline intrusion and sluices on the DOM characteristics and water quality in sluice-controlled coastal plain rivers.

Evaluation and Optimization of Quality Based on the Physicochemical Characteristics and Metabolites Changes of Qingpi during Storage.

Qingpi, the dried immature pericarp of Citrus reticulata Blanco, is a commonly used medicinal food with some health-promoting benefits. In general, it is essential that Qingpi be stored for a period of time, but there are no reports about the number of storage years needed to obtain the best quality of Qingpi. Our aim was to determine the best storage time of Qingpi by studying the physicochemical properties and metabolite changes in product stored from 1 to 5 years. As a result, the color of Qingpi became darker during storage. Both the levels of three flavonoids (hesperidin, nobiletin, and tangeretin) and total flavonoids (TFs) and the antioxidant activity decreased during storage and the total phenolics (TPs) content fluctuated during storage. Cluster analysis was performed on the color parameters measured using a color difference meter, revealing that the color of Qingpi differed before and after 3 years of storage. A total of 9 special differential metabolites were identified that could be used to distinguish the storage years of Qingpi. This is the first study to report the quality changes of Qingpi during storage. The optimized results of the quality evaluation indicated that Qingpi should be stored for no more than 3 years.

Generation of APN-chimeric gene-edited pigs by CRISPR/Cas9-mediated knock-in strategy.

The prevalence of porcine enteric coronaviruses (PECs), including transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and porcine epidemic diarrhea virus (PEDV), poses a serious threat to animal and public health. Here, we aimed to further optimize the porcine aminopeptidase N (pAPN) gene editing strategy to explore the balance between individual antiviral properties and the biological functions of pAPN in pigs. Finally, APN-chimeric gene-edited pigs were produced through a CRISPR/Cas9-mediated knock-in strategy. Further reproductive tests indicated that these gene-edited pigs exhibited normal pregnancy rates and viability. Notably, in vitro viral challenge assays further demonstrated that porcine kidney epithelial cells isolated from F1-generation gene-edited pigs could effectively inhibit TGEV infection. This study is the first to report the generation of APN-chimeric pigs, which may provide a natural host animal for characterizing PEC infection with APN and help in the development of better antiviral solutions.

Gender Discrimination of Flower Buds of Mature Populus tomentosa by HPLC Fingerprint Combined with Chemometrics.

A high performance liquid chromatography-diode array detector (HPLC-DAD) was used to establish the HPLC fingerprint. Chemometrics methods were used to discriminate against the gender of flower buds of Populus tomentosa based on areas of common peaks calibrated with the HPLC fingerprint. The score plot of principal component analysis (PCA) showed a clear grouping trend (R 2 X, 0.753; Q 2, 0.564) between female and male samples. Two groups were also well discriminated with orthogonal partial least squares-discriminant analysis (OPLS-DA) (R 2 X, 0.741; R 2 Y, 0.980; Q 2, 0.970). As the hierarchical clustering analysis (HCA) heatmap showed, all samples were separated into two groups. Four compounds were screened out by S-plot and variable importance in projection (VIP > 1.0). Two of them were identified as siebolside B and tremulacin. This study demonstrated that HPLC fingerprints combined with chemometrics can be applied to discriminate against dioecious plants and screen differences, providing a reference for identifying the gender of dioecious plants.

The Difference of Volatile Compounds in Female and Male Buds of Trichosanthes anguina L. Based on HS-SPME-GC-MS and Multivariate Statistical Analysis.

Trichosanthes anguina L. (family Cucurbitaceae) is a monoecious and diclinous plant that can be consumed as a vegetable and has anti-inflammatory and antioxidant effects. The chemical composition and content of volatile compounds in female and male buds of T. anguina were explored by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology combined with multivariate statistical analysis. The results showed that the content of the volatile compounds was different between female and male buds. 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol and 2,2,6-trimethyl-6-vinyldihydro-2H-pyran-3(4H)-one were the main volatile compounds in both female and male buds. Based on the multivariate statistical analysis of orthogonal projections to latent structures discriminant analysis (OPLS-DA) and t-test, the content of seven compounds was significantly different between female and male buds. The content of three compounds in male buds was higher than that in female, i.e., (E)-4,8-dimethyl-1,3,7-nonatriene, 1,5,9,9-tetramethyl-1,4,7-cycloundecatriene, and (E)-caryophyllene. Conversely, the content of (Z)-4-hexen-1-ol, (Z)-3-hexenyl benzoate, (Z)-3-hexenyl salicylate, and 2-hexen-1-ol in female buds was higher than that in male buds. This is the first report on the difference in the volatile compounds between female and male buds of T. anguina, which enriches the basic research on the monoecious and diclinous plant and provides a reference for the study of plant sex differentiation.

Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology.

Amyloid aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles is closely associated with Alzheimer's disease (AD). Several molecular chaperones have been reported to bind Tau and impede its pathological aggregation. Recent findings of elevated levels of Hsp27 in the brains of patients with AD suggested its important role in pTau pathology. However, the molecular mechanism of Hsp27 in pTau aggregation remains poorly understood. Here, we show that Hsp27 partially co-localizes with pTau tangles in the brains of patients with AD. Notably, phosphorylation of Tau by microtubule affinity regulating kinase 2 (MARK2), dramatically enhances the binding affinity of Hsp27 to Tau. Moreover, Hsp27 efficiently prevents pTau fibrillation in vitro and mitigates neuropathology of pTau aggregation in a Drosophila tauopathy model. Further mechanistic study reveals that Hsp27 employs its N-terminal domain to directly interact with multiple phosphorylation sites of pTau for specific binding. Our work provides the structural basis for the specific recognition of Hsp27 to pathogenic pTau, and highlights the important role of Hsp27 in preventing abnormal aggregation and pathology of pTau in AD.

Comprehensive Quality Evaluation for Medicinal and Edible Ziziphi Spinosae Semen before and after Rancidity Based on Traditional Sensory, Physicochemical Characteristics, and Volatile Compounds.

To comprehensively evaluate the quality of medicinal and edible Ziziphi Spinosae Semen (ZSS, the dried ripe seeds of Ziziphus jujuba var. spinosa) before and after rancidity during storage, some indicators including traditional sensory properties, physicochemical characteristics, and volatile compounds were analyzed. As a result, compared with the normal samples, the rancid samples of ZSS produced a darker color, a bitter taste, and an irritating odor, increased moisture content, electrical conductivity, fatty oil content, and acid value, and decreased water- and alcohol-soluble extract contents and pH value. Among them, the acid value had significant difference (p < 0.01) from 3.90 of normal ZSS to 18.68 mg/g of rancid ZSS. A total of 39 volatile compounds were identified in samples, including 20 in normal ZSS and 38 compounds in rancid ZSS. Nineteen common compounds were identified in normal and rancid samples. Among them, the content of 10 compounds such as δ-limonene, (R,R)-2,3-butanediol, and (R,S)-2,3-butanediol was decreased but that of nine compounds such as acetic acid, n-octanoic acid, and n-nonanoic acid was increased in rancid ZSS. Nineteen unique compounds such as ß-phellandrene, α-pinene, and 3-carene were detected and only one compound, δ-cadinene, was not detected in rancid ZSS. In addition, eight short-chain organic acids, acetic, propanoic, butanoic, pentanoic, hexanoic, heptanoic, octanoic, and nonanoic acids, were new products in rancid ZSS, and it was speculated that the production of a series of organic acids might be the material basis of irritating odor after normal ZSS became rancid. This is the first report that a series of short-chain organic acids have been found in a rancid substance. In conclusion, there was a significant difference between normal and rancid ZSS. These indicators could be used as an early warning for judging the rancidity phenomenon of medicinal and edible ZSS. In addition, this is the first comprehensive evaluation about the rancidity process of a medicinal and edible substance.

L-Arginine enhanced perylenequinone production in the endophytic fungus Shiraia sp. Slf14(w) via NO signaling pathway.

Perylenequinones (PQ) are natural polyketides used as anti-microbial, -cancers, and -viral photodynamic therapy agents. Herein, the effects of L-arginine (Arg) on PQ biosynthesis of Shiraia sp. Slf14(w) and the underlying molecular mechanism were investigated. The total content of PQ reached 817.64 ± 72.53 mg/L under optimal conditions of Arg addition, indicating a 30.52-fold improvement over controls. Comparative transcriptome analysis demonstrated that Arg supplement promoted PQ precursors biosynthesis of Slf14(w) by upregulating the expression of critical genes associated with the glycolysis pathway, and acetyl-CoA and malonyl-CoA synthesis. By downregulating the expression of genes related to the glyoxylate cycle pathway and succinate dehydrogenase, more acetyl-CoA flow into the formation of PQ. Arg supplement upregulated the putative biosynthetic gene clusters for PQ and activated the transporter proteins (MFS and ABC) for exudation of PQ. Further studies showed that Arg increased the gene transcription levels of nitric oxide synthase (NOS) and nitrate reductase (NR), and activated NOS and NR, thus promoting the formation of nitric oxide (NO). A supplement of NO donor sodium nitroprusside (SNP) also confirmed that NO triggered promoted biosynthesis and efflux of PQ. PQ production stimulated by Arg or/and SNP can be significantly inhibited upon the addition of NO scavenger carboxy-PTIO, NOS inhibitor Nω-nitro-L-arginine, or soluble guanylate cyclase inhibitor NS-2028. These results showed that Arg-derived NO, as a signaling molecule, is involved in the biosynthesis and regulation of PQ in Slf14(W) through the NO-cGMP-PKG signaling pathway. Our results provide a valuable strategy for large-scale PQ production and contribute to further understanding of NO signaling in the fungal metabolite biosynthesis. KEY POINTS: • PQ production of Shiraia sp. Slf14(w) was significantly improved by L-arginine addition. • Arginine-derived NO was firstly reported to be involved in the biosynthesis and regulation of PQ. • The NO-cGMP-PKG signaling pathway was proposed for the first time to participate in PQ biosynthesis.

Untargeted Metabolomics Coupled with Chemometrics for Leaves and Stem Barks of Dioecious Morus alba L.

The differences in metabolites in male and female individuals of dioecious Morus alba L. (Moraceae) are usually ignored and lack study. In the present study, 58 leaves and 61 stem barks from male and female individuals were analyzed by untargeted metabolomics via headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics, including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). A total of 66 and 44 metabolites were identified from leaves and stem barks, respectively. Four and eight differential metabolites among candidate metabolites in leaves and stem barks from male and female individuals were identified. Moreover, females possessed stronger antioxidant activity than males. This is the first report where untargeted metabolomics coupled with chemometrics was used to analyze the different metabolites and to discriminate the gender of leaves and stem barks of dioecious M. alba. It provided the basis for further study of M. alba and reference value for researching dioecious plants.

The Difference of Volatile Compounds in Female and Male Buds of Herpetospermum pedunculosum Based on HS-SPME-GC-MS and Multivariate Statistical Analysis.

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H. pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as (E)-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as (Z)-3-methylbutyraldehyde oxime and benzyl alcohol. (Z)-3-methylbutyraldehyde oxime and (E)-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, (Z)-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum, which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

[Aflatoxins and fungal community distribution during harvesting and processing of Platycladi Semen].

This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.

Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson's disease.

The spread of pathological α-synuclein (α-syn) is a crucial event in the progression of Parkinson's disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn in the amyloid over monomeric state to initiate cell-to-cell transmission. However, the molecular mechanism underlying this selective binding is unknown. Here, we perform an array of biophysical experiments and reveal that LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus, especially residues 118 to 140, of α-syn. The formation of amyloid fibrils not only can disrupt the intramolecular interactions between the C terminus and the amyloid-forming core of α-syn but can also condense the C terminus on fibril surface, which remarkably increase the binding affinity of α-syn to the receptors. Based on this mechanism, we find that phosphorylation at serine 129 (pS129), a hallmark modification of pathological α-syn, can further enhance the interaction between α-syn fibrils and the receptors. This finding is further confirmed by the higher efficiency of pS129 fibrils in cellular internalization, seeding, and inducing PD-like α-syn pathology in transgenic mice. Our work illuminates the mechanistic understanding on the spread of pathological α-syn and provides structural information for therapeutic targeting on the interaction of α-syn fibrils and receptors as a potential treatment for PD.