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Identified as the pathogenic genes of Alzheimer's disease (AD), APP, PSEN1, and PSEN2 mainly lead to early-onset AD, whose course is more aggressive, and atypical symptoms are more common than sporadic AD. Here, a novel missense mutation, APP E674Q (also named “Shanghai APP”), was detected in a Chinese index patient with typical late-onset AD (LOAD) who developed memory decline in his mid-70s. The results from neuroimaging were consistent with AD, where widespread amyloid β deposition was demonstrated in 18F-florbetapir Positron Emission Tomography (PET). APP E674Q is close to the β-secretase cleavage site and the well-studied Swedish APP mutation (KM670/671NL), which was predicted to be pathogenic in silico. Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1. The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ. Furthermore, we applied an adeno-associated virus (AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice. AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain, implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation. Collectively, we report a strong amyloidogenic effect of the E674Q substitution in AD. To our knowledge, E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

Chouioia cunea are known to exploit in varying degrees a wide range of lepidopteran species and its offspring development may vary with host species. This study examined its preimaginal development and larval gut microbiota in parasitizing five folivorous lepidopteran hosts including Hyphantria cunea (referred to thereafter as CcHc), Antherea pernyi (CcAp), Helicoverpa armigera (CcHa), Spodoptera exigua (CcSe), and Spodoptera frugiperda (CcSf). Though rates of parasitism and offspring eclosion did not change with host species, the development period and number of offspring eclosed varied with hosts, with the shortest period in CcSf and the highest number from CcAp. For offspring larval gut microbiota, though phylum Proteobacteria was dominant for attacking CcAp, Firmicutes was so for the other hosts. All microbial genera except Enterococcus were less abundant for CcSf than the other hosts. The database-based predictions indicate a significant positive correlation between Cutibacterium and Aureimonas with the relative number of wasp emergence, while Blastomonas exhibits a strong positive association with the developmental period. Our results imply the potential relevance of the gut microbial community in offspring larvae to host species attacked by C. cunea.

Insufficient milk supply is a widespread issue faced by women globally and associated with a higher risk of health problems in infants and mothers. Hemerocallis citrina Baron, commonly known as daylily, is a perennial edible plant often used in traditional Asian cuisine to promote lactation. However, the active compound(s) and mechanism of its lactation-promoting effect remain unclear. This study aimed to confirm the traditional use of daylily in promoting lactation and investigate its potential active components and underlying molecular mechanisms. Our results showed that the aqueous extracts of H. citrina Baroni (HAE) significantly enhanced milk production, and the serum levels of lactation-related hormones, and promoted mammary gland development in lactating rats, as well as increased the levels of milk components in bovine mammary epithelial cells (BMECs) (p < 0.05). UHPLC-Q-Exactive Orbitrap-MS analysis revealed that hexamethylquercetin (HQ) is the representative flavonoid component in HAE, accounting for 42.66% of the total flavonoids. An integrated network pharmacology and molecular docking analysis suggested that HQ may be the potential active flavonoid in HAE that promotes lactation, possibly supporting lactation by binding to key target proteins such as STAT5A, PIK3CA, IGF1R, TP53, CCND1, BCL2, INS, AR, and DLD. Cell experiments further demonstrated that HQ could promote cell proliferation and the synthesis of milk proteins, lactose, and milk fat in BMECs. Transcriptomic analysis combined with a quantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed that both HAE and HQ exert a lactation-promoting function mainly through regulating the expression of key genes in the PI3K-Akt signaling pathway.

Wild-type strains hardly meet the current industrial demands due to low stability. The performance of microbial strains (high-yielding, high-quality strains) can be improved by using physical mutagenesis techniques. At the same time，high throughput screening methods and techniques can be used to quickly obtain ideal strains from the mutation library. However, traditional manual screening and shaker culture are high-cost, time-consuming, and laborious, and high-throughput screening technology can solve this problem. In this review, the applications of traditional and novel mutagenesis used for the improvement of probiotics are summarized, the principles of traditional and novel physical mutagenesis techniques are discussed, the differences between the two kinds of mutagenesis techniques are compared and their applications in the improvement of probiotics are described. At the same time, the characteristics and relevant applications of various high-throughput screening technologies (microtitration plate screening, fluorescence activated cell sorting, biosensors screening, droplet microfluidic platform screening and model animal platform screening) are summarized. This review provides important reference for reducing screening cost, improving screening efficiency and obtaining high yield ideal target strains.

ABSTRACT: Yak milk is rich in essential milk proteins of nutritional and therapeutic value. In this study, whey proteins of milk from 3 yak breeds (Gannan, GN; Huanhu, HH; Maiwa, MW) in China were comprehensively identified and compared using a data-independent acquisition quantitative proteomics approach. A total of 632 proteins were identified in yak milk whey samples, in which immune-related proteins were abundant. Compared with other milks, more proteins were involved in oxidation-reduction process and with ATP binding. In addition, we identified 96, 155, and 164 differentially expressed proteins (DEP) for GN versus HH, GN versus MW, and HH versus MW, respectively. “Phagosome” and “complement and coagulation cascades” were the most significant pathways for DEP of GN versus HH and GN or HH versus MW yak milk based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein-protein interaction network analysis showed that DEP for the 3 comparisons had significant biological interactions but were associated with different functions. The results provide useful information on yak milk from different breeds in China, and elucidate the biological functions of yak milk proteins.

ObjectivesOne-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women.MethodsData were obtained from the baseline of the Mother–Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24–32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire.ResultsOf 397 participants, 82.6% were in mid-pregnancy (24–27 gestational weeks) and 17.4% were in late-pregnancy (28–32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p

With the continuous improvement of people's living standards and health awareness, more and more attention has been paid to food safety. It follows that the research and management of the types and labels of food allergens also need to be more and more strict. Therefore, the regulation of food allergens needs to be more and more stringent. This summary reviews the current status of food allergen testing methods and standards in China. Also, the labelling of food allergen types in China, the Codex Alimentarius Commission, the United States, the European Union, Canada and Japan is systematically summarized. By systematically reviewing the labeling management of food allergens in various countries and regions, it is hoped to provide reference for Chinese food allergen labeling management, and to continuously improve our country's food allergen detection methods and labeling standards.

IntroductionIn this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals.MethodsWe collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated.ResultsIn this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p

In recent years, oncolytic viruses (OVs) have emerged as an effective means of treating cancer. OVs have multiple oncotherapeutic functions including specifically infecting and lysing tumor cells, initiating immune cell death, attacking and destroying tumor angiogenesis and triggering a broad bystander effect. Oncolytic viruses have been used in clinical trials and clinical treatment as drugs for cancer therapy, and as a result, oncolytic viruses are required to have long-term storage stability for clinical use. In the clinical application of oncolytic viruses, formulation design plays a decisive role in the stability of the virus. Therefore, this paper reviews the degradation factors and their degradation mechanisms (pH, thermal stress, freeze–thaw damage, surface adsorption, oxidation, etc.) faced by oncolytic viruses during storage, and it discusses how to rationally add excipients for the degradation mechanisms to achieve the purpose of maintaining the long-term stability of oncolytic viral activity. Finally, the formulation strategies for the long-term formulation stability of oncolytic viruses are discussed in terms of buffers, permeation agents, cryoprotectants, surfactants, free radical scavengers, and bulking agent based on virus degradation mechanisms.

Parkinson's disease (PD) is the most common motor-associated neurodegenerative disease. Although the pathogenesis of PD is still wrapped in the mist, accumulating evidence indicates that mitochondrial dysfunction contributes to the onset and progression of PD. We previously reported that the lysosomal protease asparagine endopeptidase (AEP) cleaves α-synuclein in the brains of PD patients. The major product, α-synuclein 1–103, significantly promotes PD-like histological changes and motor dysfunction. However, the underlying molecular mechanisms remain unknown. Here we show that α-synuclein 1–103 fragment interacts with mitochondria and induces morphological and functional abnormalities of mitochondria. Furthermore, we investigated the protective effects of 7,8-dihydroxyflavone (7,8-DHF) on mitochondrial dysfunction induced by α-synuclein 1–103 fragment. We found that 7,8-DHF ameliorated α-synuclein 1–103-induced mitochondrial impairment and motor dysfunction. These results indicate that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating PD.

Abstract Background Maternal feeding anxiety (FA) was prevalent during puerperium and might affect infant feeding practices. This study was aimed to investigate the FA status in Chinese postpartum women and its relationship with infant feeding practices (FPs). Methods Participants were from the Mother-Infant Cohort Study of China, in which the dietary and feeding practices, physical and psychiatric health for both mothers and infants were followed up from childbirth to next 2 years. In this study the maternal feeding anxiety (FA) status at 0–3 months postpartum was assessed by Li’s Self-rating Feeding Anxiety Scale (SFAS). Infant feeding practices (FPs) at 0–3 months, including breastfeeding-related behaviors, responsive feeding and infant food refusal were investigated by self-designed questionnaire. Results In total 456 mothers the average feeding anxiety scores (FAS) was 41.02 ± 8.02 (mean ± SD), and maternal FA prevalence were 61.4% (FAS>38) with severe FA being 8.6% (FAS>52) at 0–3 months postpartum. The FAS was related with infant FPs, and lower maternal FAS was significantly related with infant colostrum feeding (40.86 ± 8.02 vs 44.74 ± 11.33, P 53) were more likely to feed infants with bottle (ORs, 95%CI: 2.41, 1.11 ~ 5.19). There were not significant association between FAS and exclusive breastfeeding and responsive feeding practices (P > 0.05). The higher FAS was associated with infant food refusal behaviors, the maternal scores whose infant “never”, “rarely”, “sometimes” and “often” spat out food when feeding were 39.86 ± 8.02, 41.47 ± 8.18, 41.36 ± 7.44 and 42.14 ± 12.03 increasingly (P > 0.05), and the FA prevalence was significantly different among groups (P

The FLT3-ITD mutation occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor prognosis. However, FLT3 inhibitors are only partially effective and prone to acquired resistance. Here, we identified Yes-associated protein 1 (YAP1) as a tumor suppressor in FLT3-ITD+ AML. YAP1 inactivation conferred FLT3-ITD+ AML cell resistance to chemo- and targeted therapy. Mass spectrometric assay revealed that DNA damage repair gene poly (ADP-ribose) polymerase 1 (PARP1) might be the downstream of YAP1, and the pro-proliferative effect by YAP1 knockdown was partly reversed via PARP1 inhibitor. Importantly, histone deacetylase 10 (HDAC10) contributed to decreased YAP1 acetylation levels through histone H3 lysine 27 (H3K27) acetylation, leading to the reduced nuclear accumulation of YAP1. Selective HDAC10 inhibitor chidamide or HDAC10 knockdown activated YAP1, enhanced DNA damage, and significantly attenuated FLT3-ITD+ AML cell resistance. In addition, combination chidamide with FLT3 inhibitors or chemotherapy agents synergistically inhibited growth and increased apoptosis of FLT3-ITD+ AML cell lines and acquired resistant cells from the relapse FLT3-ITD+ AML patients. These findings demonstrate that the HDAC10-YAP1-PARP1 axis maintains FLT3-ITD+ AML cells and targeting this axis might improve clinical outcomes in FLT3-ITD+ AML patients.

Hypertension is a major risk factor leading to cardiovascular disease, and is frequently treated with angiotensin I-converting enzyme (ACE) inhibitory peptides. The objective of this study was to separate and identify an ACE-inhibitory peptide from goat milk casein hydrolysates, and to evaluate its potential for improving angiotensin II (Ang II)-mediated adverse effects on vascular smooth muscle cells (VSMCs). A novel ACE-inhibitory peptide with the highest activity from the goat milk casein hydrolysates as determined by four steps of RP-HPLC was purified and identified as Phe-Pro-Gln-Tyr-Leu-Gln-Tyr-Pro-Tyr (FPQYLQYPY). The results of inhibitory kinetics studies indicated that the peptide was a non-competitive inhibitor against ACE. Gastrointestinal digest in vitro analysis showed that the hydrolysate of FPQYLQYPY was still active after digestion with gastrointestinal proteases. Moreover, we found that the peptide could significantly inhibit the proliferation and migration of Ang II-stimulated VSMCs. Further transcriptomic analysis revealed that differentially expressed genes (DEGs) were enriched in the cardiovascular disease-related pathways, and that the peptide may have the ability to regulate vascular remodeling. Our findings indicate the potential anti-hypertensive effects of FPQYLQYPY, as well-implicate its role in regulating vascular dysfunction.

Aiming at the problems of poor classification effect, low accuracy, and long time in the current automatic classification methods of music genres, an automatic classification method of music genres based on deep belief network and sparse representation is proposed. The music signal is preprocessed by framing, pre-emphasis, and windowing, and the characteristic parameters of the music signal are extracted by Mel frequency cepstrum coefficient analysis. The restricted Boltzmann machine is trained layer by layer to obtain the connection weights between layers of the depth belief network model. According to the output classification, the connection weights in the model are fine-tuned by using the error back-propagation algorithm. Based on the deep belief network model after fine-tuning training, the structure of the music genre classification network model is designed. Combined with the classification algorithm of sparse representation, for the training samples of sparse representation music genre, the sparse solution is obtained by using the minimum norm, the sparse representation of test vector is calculated, the category of training samples is judged, and the automatic classification of music genre is realized. The experimental results show that the music genre automatic classification effect of the proposed method is better, the classification accuracy rate is higher, and the classification time can be effectively shortened.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. However, its cellular and molecular mechanisms still wrap in the mist. This is partially caused by the absence of appropriate animal models mimicking sporadic PD that constitutes the majority of cases. Previously, we reported that a cysteine protease, asparagine endopeptidase (AEP), is activated in an age-dependent manner, and cleaves α-synuclein in the brain of sporadic PD patients. The AEP-derived α-synuclein 1-103 fragment is required for the pathogenesis of PD. Thus, we designed and characterized a novel transgenic mouse line expressing α-synuclein 1-103 (designated N103 mice). This model shows an abundant accumulation of pathological α-synuclein in the central nervous system, loss of dopaminergic neurons in the substantia nigra, and progressive striatal synaptic degeneration. The N103 mice also manifest age-dependent PD-like behavioral impairments. Notably, the mice show weight loss and constipation, which are the common non-motor symptoms in PD. The RNA-sequencing analysis found that the transcriptomics pattern was extensively altered in N103 mice. In conclusion, the N103 mouse line, as a brand-new tool, might provide new insights into PD research.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway. Synaptic dysfunction impairs dopamine turnover and contributes to the degeneration of dopaminergic neurons. However, the molecular mechanisms underlying synaptic dysfunction and dopaminergic neuronal vulnerability in PD are not clear. Here, we report that synaptojanin 1 (SYNJ1), a polyphosphoinositide phosphatase concentrated at nerve terminals, is a substrate of a cysteine proteinase, asparagine endopeptidase (AEP). SYNJ1 is cleaved by the cysteine proteinase AEP at N599 in the brains of PD patients. AEP-mediated cleavage of SYNJ1 disrupts neuronal phosphoinositide homeostasis and causes synaptic dysfunction. Overexpression of the AEP-generated fragments of SYNJ1 triggers synaptic dysfunction and the degeneration of dopaminergic neurons, inducing motor defects in the α-synuclein transgenic mice. Blockage of AEP-mediated cleavage of SYJN1 alleviates the pathological and behavioral defects in a mouse model of PD. Our results demonstrate that the fragmentation of SYNJ1 by AEP mediates synaptic dysfunction and dopaminergic neuronal degeneration in PD.

Neurofibrillary tangles composed of hyperphosphorylated tau and synaptic dysfunction are characteristics of Alzheimer’s disease (AD). However, the underlying molecular mechanisms remain poorly understood. Here, we identified Amphiphysin I mediates both tau phosphorylation and synaptic dysfunction in AD. Amphiphysin I is cleaved by a cysteine proteinase asparagine endopeptidase (AEP) at N278 in the brains of AD patients. The amount of AEP-generated N-terminal fragment of Amphiphysin I (1-278) is increased with aging. Amphiphysin I (1-278) inhibits clathrin-mediated endocytosis and induces synaptic dysfunction. Furthermore, Amphiphysin I (1-278) binds p35 and promotes its transition to p25, thus activates CDK5 and enhances tau hyperphosphorylation. Overexpression of Amphiphysin I (1-278) in the hippocampus of Tau P301S mice induces synaptic dysfunction, tau hyperphosphorylation, and cognitive deficits. However, overexpression of the N278A mutant Amphiphysin I, which resists the AEP-mediated cleavage, alleviates the pathological and behavioral defects. These findings suggest a mechanism of tau hyperphosphorylation and synaptic dysfunction in AD.

Chironomidae is the most ecologically diverse insects in aquatic and semi-aquatic habitats. Propsilocerus akamusi (Tokunaga) is a dominant and ubiquitous chironomid species in Eastern Asia and its morphologically unique larvae are also considered as indicator organisms to detect water contamination, potential toxicity and waterborne pathogens. Since few studies to date have focused on the olfactory system of P. akamusi, our study aims to elucidate the potential functions of chemosensory genes in P. akamusi. In our study, we found that although signals released from male groups might attract female swarmers, it was a completely male-dominated mating process. Sequencing the transcriptome of P. akamusi on an Illumina HiSeq platform generated 4.42, 4.46 and 4.53 Gb of clean reads for heads, legs, and antennae, respectively. 27,609 unigenes, 20,379 coding sequences (CDSs), and 8,073 simple sequence repeats were finally obtained. The gene-level differential expression analysis demonstrated variants among three different tissues, including 2,019 genes specifically expressed in heads, 1,540 genes in legs, and 2,071 genes in antennae. Additionally, we identified an assortment of putative olfactory genes consisting of 34 odorant binding proteins, 17 odorant receptors, 32 gustatory receptors, 22 ionotropic receptors, six chemosensory proteins as well as 3 sensory neuron membrane proteins; their relative abundances in the above three tissues were also determined by RT-qPCR. Our finding could allow a more plausible understanding of certain olfaction-mediated behaviors in groups of this macroinvertebrate.

Diet is believed to play a major role in maternal recovery, postpartum weight retention (PPWR) is one of the challenges for Chinese women. However, the association between puerperal women's diet and PPWR remained unclear and complicated in China. The study assessed the dietary quality of puerperal women using adjusted Chinese Dietary Balance Index-16 (DBI-16) and explored its associations with PPWR. Participants were enrolled in the Mother-Infant Cohort Study of China. Dietary intake and demographic characteristics were obtained by a semi-quantitative food frequency questionnaire and a self-designed questionnaire at 0-3 months postpartum. PPWR was calculated by the weight difference at 0-3months and 6-8months postpartum minus pre-pregnancy weight. Dietary quality was assessed using adjusted DBI-16. 316 puerperal women were enrolled. According to adjusted DBI-16, 84.8% of participants had an insufficient dietary intake (vegetables 84.8%, fruits 91.8%, dairy 87.3%, soybean 61.4% and aquatic foods 79.4%, respectively), 67.1% had an excessive intake (cereals 60%, meat 57.3% and eggs 64.9%, respectively), 98.4% had an imbalanced diet consumption. PPWR at 0-3, and 6-8 months were 6.0 (±5.1) kg and 5.2 (±7.7) kg, and the percentage of PPWR (≥5kg) were 63.0% and 52.8% respectively. Multivariable linear regression showed the intake of fish and shrimp at 0-3 months postpartum was negatively associated with PPWR at 6-8 months (β = -0.114, SE = 0.279, p < 0.05). The diet quality of Chinese puerperal women was unreasonable and imbalanced. Fish intake tended to be a favorable factor for postpartum weight loss.