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Mitochondrial unfolded protein response plays an important role in the occurrence and development of breast cancer. However, the role of mitochondrial unfolded protein response (UPRmt) in the sensitivity of breast cancer to cisplatin chemotherapy has not yet been cleared. The purpose of this study is to explore the role of mitochondrial unfolded protein response in breast cancer sensitivity to cisplatin. In this study, qRT-PCR, Western blotting, Immunofluorescence, CCK-8, Colony formation, Transwell assay and TUNEL staining assay were used to confirm the role of UPRmt in breast cancer cells treated with cisplatin. Cisplatin increased the levels of UPRmt including CLPP, HSP60, LONP1 in MCF7 and MDA-MB-231 cells. UPRmt inducer Nicotinamide ribose (NR) could promote the proliferation and invasion of breast cancer cells treated with cisplatin. Importantly, SIRT3 was discovered to increase UPRmt in breast cancer cells and silencing of SIRT3 could inhibit the effect of NR in breast cancer. UPRmt regulated by SIRT3 could protect breast cancer cell from cisplatin. Controlling SIRT3-induced UPR may be a potential therapeutic target to increase the sensitivity of breast cancer chemotherapy.

Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, and oral infection. Due to the lack of long-term treatment for the symptoms of xerostomia, current research has focused on finding endogenous stem cells that can differentiate into various cell lineages to replace lost tissue and restore functions. Here, we report that Sox9+ cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9+ cells, the salivary glands of irradiated mice showed more severe phenotypes and the reduced proliferative capacity. Analysis of online single-cell RNA-sequencing data reveals the enrichment of the Wnt/β-catenin pathway in the Sox9+ cell population. Furthermore, treatment with a Wnt/β-catenin inhibitor in irradiated mice inhibits the regenerative capability of Sox9+ cells. Finally, we show that Sox9+ cells are capable of forming organoids in vitro and that transplanting these organoids into salivary glands after radiation partially restored salivary gland functions. These results suggest that regenerative therapy targeting Sox9+ cells is a promising approach to treat radiation-induced salivary gland injury.

Background LINC00152 (long intergenic non-protein coding RNA 152) was identified as an oncogenic lncRNA in multiple cancers. In the current study, we aimed to explore the transcriptional profile of LINC00152 in oral squamous cell carcinoma (OSCC) and its regulations at the transcriptional level. Methods Bioinformatic analysis was performed by extracting the OSCC subset from The Cancer Genome Atlas (TCGA)-Head and Neck Squamous Cell Carcinoma (HNSC). LINC00152 subcellular localization and its interacting transcriptional factors (TFs) were explored. Dual-luciferase assay and ChIP-qPCR were applied to study transcriptional regulation. In vitro and in-vivo tumor cell growth models were used for functional assays. Results NR_024206.2 was the dominant isoform that accounts for 80% of all transcripts of LINC00152. LINC00152 upregulation was associated with unfavorable survival of patients with OSCC. LINC00152 knockdown significantly impaired OSCC cell growth in vitro and in vivo. RNA FISH assay confirmed nuclear and cytoplasmic distribution of LINC00152. It physically interacted with Upstream Transcription Factor 1 (USF1), a common transcription factor in mammalian cells. USF1 could bind to the promoter region of MRPL52 (Mitochondrial Ribosomal Protein L52) and activate its transcription. LINC00152 could enhance the binding, thereby indirectly elevating MRPL52 expression. USF1 or MRPL52 knockdown slowed the proliferation of OSCC cells and partly canceled LINC00152 mediated growth-promoting effects. Conclusion This study revealed a novel LINC00152-USF1/MRPL52 axis promoting OSCC tumor growth.

Azole resistance constitutes a serious clinical problem in the management of infections caused by Candida albicans. This study aimed to explore azole-resistant mechanisms in clinical C. albicans isolates collected in Jinan, Shandong, China. In total, 22 samples were collected and analyzed. Among these, four isolates (28A, 28D, 28I, and 28J) exhibited high level of pan-azole-resistance that was Hsp90 dependent. Gene sequencing revealed that the four Hsp90-dependent strains contained different ERG3 mutations that led to four novel amino acid substitutions (S265Y, N322D, N324S, and E355D) in Erg3. The role of these substitutions in azole resistance development was determined by constructing one copy of the mutated ERG3 from the 28A, 28D, and 28I strains into C. albicans CAI4, respectively. The minimum inhibitory concentration value of fluconazole (FLC) against C. albicans CAI4-ERG328I increased fourfold compared with the wild-type C. albicans strain, suggesting that the novel combination of substitutions S265Y, N322D, and N324S played an important role in mediating azole resistance in 28I. Besides, we identified several different mechanisms in other three isolates. Strains 28A and 28D displayed increased efflux ability and overexpression of MDR1. Strain 28J showed high level of ERG11 expression, but no mutation in its regulator Upc2 was observed. Our study revealed that multiple factors confer azole resistance in clinical C. albicans isolates and combination therapy should be conducted clinically.

Aims To analyze changes in oropharynx microbiota composition after receiving induced chemotherapy followed by surgery for hypopharyngeal squamous cell carcinoma (HPSCC) patients. Methods Clinical data and swab samples of 38 HPSCC patients (HPSCC group) and 30 patients with benign disease (control group, CG) were enrolled in the study. HPSCC group was stratified into two groups: induced chemotherapy group (IC) of 10 patients and non-induced chemotherapy group (nIC) of 28 patients. The microbiota from oropharyngeal membrane was analyzed through 16S rRNA sequencing. Results Alpha-diversity (Shannon and Ace indexes) and weighted UniFrac based beta-diversity severely decreased in the HPSCC group when compared with CG. In pre-operative comparisons, PCoA and NMDS analyses showed microbial structures in the IC group were more similar to CG than nIC. Both IC group and nIC group yielded significantly diverse post-operative communities in contrast to their pre-operative counterparts, evident by the decrease in genera Veillonella and Fusobacterium and increase in genera Streptococcus and Gemella. Given that post-operative oropharynx microbiota showed no difference between IC and nIC groups, the IC group showed less accumulation in anaerobic communities. The abundance of genera Fusobacterium, Parvimonas, Actinomyces were enhanced in the advanced stages (III/IV). Conclusions Oropharynx microbiota in the HPSCC group presents dysbiosis with low diversity and abundance. Induced chemotherapy is beneficial in adjusting the oropharynx microbial environment leading to fewer amounts of anaerobe accumulation after operation. Higher amounts of Fusobacterium in advanced stages (III/IV) may influence the progression of HPSCC.

Spindle and Kinetochore Associated Complex Subunit 3 (SKA3) is crucial for anaphase mitosis. However, the relationship between SKA3 and lung adenocarcinoma (LUAD) has not been fully clarified. Differentially expressed genes were first identified by analyzing data from TCGA. It was found that miR-133b was significantly lowly expressed in LUAD, while SKA3 was remarkably highly expressed. Cell Counting Kit-8 (CCK8), wound healing assay and Transwell assay uncovered that overexpressing miR-133b could inhibit the proliferation, invasion and migration of LUAD cells. In addition, the targeting relationship between miR-133b and SKA3 was also verified by dual-luciferase analysis. Moreover, it was proved by the rescue assay that the overexpression of miR-133b significantly downregulated SKA3 in LUAD cells. All in all, these findings revealed the role of miR-133b and SKA3 in regulating the proliferation, migration, and invasion of LUAD cells. This study could yield new information about the mechanisms of LUAD.

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1β and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.

A NIR fluorescent probe (DDAA) derived from fluorophore DDAO with alanine as the recognition group was developed for sensing aminopeptidase N (APN) in gut microbiota. Using DDAA as the real-time guidance tool for the fluorescence imaging of intestinal microorganism, target bacteria and saccharomycete possessing active APN were identified successfully from human feces.

Recent studies suggest that RRP15 (Ribosomal RNA Processing 15 Homolog) might be a potential target for cancer therapy. However, the role of RRP15 in hepatocarcinogenesis remains poorly delineated. In this study, we aimed to evaluate the expression and biological function of RRP15 in human hepatocellular carcinoma (HCC). We show that RRP15 was up regulated in HCC cell lines and tumours. Up-regulation of RRP15 in HCC tumours was also correlated with unfavorable prognosis. We further show that the frequent up-regulation of RRP15 in HCCs is at least partly driven by recurrent gene copy gain at chromosome 1q41. Functional studies indicated that RRP15 knockdown suppresses HCC proliferation and growth both in vitro and in vivo. Mechanistically, RRP15 depletion in p53-wild-type HepG2 cells induced senescence via activation of the p53-p21 signalling pathway through enhanced interaction of RPL11 with MDM2, as well as inhibition of SIRT1-mediated p53 deacetylation. Moreover, RRP15 depletion in p53-mutant PLC5 and p53-deleted Hep3B cells induced metabolic shift from the glycolytic pentose-phosphate to mitochondrial oxidative phosphorylation via regulating a series of key genes such as HK2 and TIGAR, and thus, promoted the generation of ROS and apoptosis. Taken together, our findings provide evidence for an important role of the RRP15 gene in hepatocarcinogenesis through regulation of HCC proliferation and growth, raising the possibility that targeting RRP15 may represent a potential therapeutic strategy for HCC treatment.

The activating transcription factor 1 (ATF1) has been identified as a vital pathogenic factor in the progression of colorectal cancer (CRC), whiles, the precise regulatory mechanisms remain elusive. Here, we comprehensively characterized the ATF1 cistrome by RNA-seq and ChIP-seq assays in CRC cell lines. As the results, we identified 358 genes differentially regulated and 15,029 ATF1 binding sites and demonstrated that ATF1 was widely involved in major signaling pathways in CRC, such as Wnt, TNF, Jak-STAT. Subsequently, by the expression quantitative trait loci (eQTL) analyses, we found that rs7017386 was associated with the expression of CCAT1 and PVT1 in the Wnt pathway. By a two-stage population study with 6,131 CRC cases and 10,022 healthy controls, we identified the variant was associated with CRC risk. Mechanistically, we found rs7017386 allele-specifically enhanced the binding affinity of ATF1 and promoted the expressions of PVT1 and CCAT1, via forming a long-range chromatin loop. Moreover, those two lncRNAs could synergistically facilitate c-Myc expression to activate the Wnt pathway in CRC progression. Our findings not only demonstrated the transcriptomic profiling of ATF1 in CRC, but also provided important clues for the etiology of CRC.

Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remains unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium-related disorders. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The genetic variants of orosomucoid-like protein 3 (ORMDL3) gene are associated with highly significant increases in the number of human rhinovirus (HRV)-induced wheezing episodes in children. Recent investigations have been focused on the mechanisms of ORMDL3 in rhinovirus infection for asthma and asthma exacerbations. ORMDL3 not only regulates major human rhinovirus receptor intercellular adhesion molecule 1 expression, but also plays pivotal roles in viral infection through metabolisms of ceramide and sphingosine-1-phosphate, endoplasmic reticulum (ER) stress, ER-Golgi interface and glycolysis. Research on the roles of ORMDL3 in HRV infection will lead us to identify new biomarkers and novel therapeutic targets in childhood asthma and viral induced asthma exacerbations.

Summary Recent advances in plant genomics are scaling up gene expression profiling from the individual level to the population level, making transcriptomics a more powerful tool while deciphering the genome function. This study developed an efficient 3′RNA‐seq method, Simplified Poly(A) Anchored Sequencing (SiPAS), to perform large‐scale experiments of gene expression quantification. Aside from being cost‐effective, by conducting a comprehensive performance assessment of SiPAS in hexaploid wheat, we demonstrated that SiPAS is highly sensitive, accurate, and reproducible while quantifying gene expression. Our method is anticipated to boost studies of population transcriptomics in plants and improve our understanding of genome biology.

A released exopolysaccharide (rEPS)-producing strain (LM187) with good acid resistance, bile salt resistance, and cholesterol-lowering properties was isolated from Sichuan paocai and identified as Leuconostoc mesenteroides subsp. mesenteroides. The purified rEPS, designated as rEPS414, had a uniform molecular weight of 7.757 × 105 Da. Analysis of the monosaccharide composition revealed that the molecule was mainly composed of glucose. The Fourier transform-infrared spectrum showed that rEPS414 contained both α-type and β-type glycosidic bonds. 1H and 13C nuclear magnetic resonance spectra analysis showed that the purified rEPS contained arabinose, galactose, and rhamnose, but less uronic acid. Scanning electron microscopy demonstrated that the exopolysaccharide displayed a large number of scattered, fluffy, porous cellular network flake structures. In addition, rEPS414 exhibited strong in vitro antioxidant activity. These results showed that strain LM187 and its rEPS are promising probiotics with broad prospects in industry.

Hand, foot, and mouth disease (HFMD) is a contagious disease that threatens the health of children under 5 years of age. Coxsackievirus A10 (CV-A10) is one of the main pathogens of HFMD. Currently, preventive vaccines and specific therapeutic drugs are not available for CV-A10. In this study, a total of 327 stool specimens were collected from pediatric patients from 2009 to 2017 during HFMD surveillance, among which 14 CV-A10 strains could only be isolated from rhabdomyosarcoma cells, but not from KMB17 and Vero cells. Through adaptive culture, 2 and 11 CV-A10 strains were recovered from Vero and KMB17 cell cultures, respectively. The growth of CV-A10 strains in Vero cells was better than that in KMB17 cells. The 14 CV-A10 strains belonged to the F genotype, and the nucleotides and amino acids of their complete genomes shared 92.6%-96.3% and 98.4%-98.9% identities, respectively. The different CV-A10 strains exhibited varying virulence in vivo, but had similar effects on tissue injury, with the hind limb muscles, kidneys, and lungs being severely affected. Additionally, the hind limb muscles had the highest viral loads. CV-A10 was found to exhibit a strong tropism to muscle tissue. The results of this study are critical to developing vaccines against CV-A10 infections.

Leucine aminopeptidase (LAP) is a hydrolase for the hydrolysis of peptides or proteins containing a leucine residue at the N-terminal. It is also known to be a key virulence factor for the pathogenic abilities of various pathogens causing infectious diseases, which indicated a new insight into the diagnosis and therapy of pathogenic infections. A new fluorescent probe (S)-2-amino-N-(4-(((6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl)oxy)methyl)phenyl)-4-methylpentanamide (DDBL) containing DDAO as the fluorophore and leucine as the recognition group was developed for LAP. By real-time visual sensing of LAP, six bacteria with LAP expression were identified efficiently from human feces, as well as by sensitive visual analysis using native-PAGE specially stained with DDBL. Furthermore, a high throughput screening system established with DDBL was applied to identify a natural inhibitor (3-acetyl-11-keto-β-boswellic acid, AKBA), which could attenuate mouse sepsis induced by Staphylococcus aureus. Therefore, the visual sensing of LAP by DDBL suggested the application for target bacteria identification and LAP homolog analysis as well as potential inhibitor expounding for treatment of bacterial infections.

Reports of immune-related adverse events caused by programmed cell death protein-1 inhibitor are becoming increasingly frequent. Herein, we report the first case of pemphigus herpetiformis-type drug reaction presented after the treatment of tislelizumab (6 cycles) in a primary non-small cell lung carcinoma patient. A 56-year-old Chinese man was referred to our department for pruritic annulare erythema and blister for two weeks. Histological finding revealed blister formation in the epidermis and eosinophilic infiltration in the blister fluid. Direct immunofluorescence showed intercellular deposition of IgG and C3 within the lower part of epidermis. Serum anti-intercellular antibodies were positive at 1:100 dilution. Based on history and clinicopathological correlation, herpetiformis-type drug-induced pemphigus was diagnosed, which was possibly be induced by tislelizumab. To the best to our knowledge, there is no report of pemphigus herpetiformis-type drug-induced reaction associated with programmed cell death protein-1 inhibitor treatment.

Background Cryopreservation induces transcriptomic and epigenetic modifications that strongly impairs sperm quality and function, and thus decrease reproductive performance. N6-methyladenosine (m6A) RNA methylation varies in response to stress and has been implicated in multiple important biological processes, including post-transcriptional fate of mRNA, metabolism, and apoptosis. This study aimed to explore whether cryopreservation induces m6A modification of mRNAs associated with sperm energy metabolism, cryoinjuries, and freezability. Results The mRNA and protein expression of m6A modification enzymes were significantly dysregulated in sperm after cryopreservation. Furthermore, m6A peaks were mainly enriched in coding regions and near stop codons with classical RRACH motifs. The mRNAs containing highly methylated m6A peaks (fts vs. fs) were significantly associated with metabolism and gene expression, while the genes with less methylated m6A peaks were primarily involved in processes regulating RNA metabolism and transcription. Furthermore, the joint analysis of DMMGs and differentially expressed genes indicated that both of these play a vital role in sperm energy metabolism and apoptosis. Conclusions Our study is the first to reveal the dynamic m6A modification of mRNAs in boar sperm during cryopreservation. These epigenetic modifications may affect mRNA expression and are closely related to sperm motility, apoptosis, and metabolism, which will provide novel insights into understanding of the cryoinjuries or freezability of boar sperm during cryopreservation.

Although Uzbekistan and Central Asia are known for the well-studied Bronze Age civilization of the Bactria–Margiana Archaeological Complex (BMAC), the lesser-known Iron Age was also a dynamic period that resulted in increased interaction and admixture among different cultures from this region. To broaden our understanding of events that impacted the demography and population structure of this region, we generated 27 genome-wide single-nucleotide polymorphism capture data sets of Late Iron Age individuals around the Historical Kushan time period (∼2100–1500 BP) from three sites in South Uzbekistan. Overall, Bronze Age ancestry persists into the Iron Age in Uzbekistan, with no major replacements of populations with Steppe-related ancestry. However, these individuals suggest diverse ancestries related to Iranian farmers, Anatolian farmers, and Steppe herders, with a small amount of West European Hunter Gatherer, East Asian, and South Asian Hunter Gatherer ancestry as well. Genetic affinity toward the Late Bronze Age Steppe herders and a higher Steppe-related ancestry than that found in BMAC populations suggest an increased mobility and interaction of individuals from the Northern Steppe in a Southward direction. In addition, a decrease of Iranian and an increase of Anatolian farmer-like ancestry in Uzbekistan Iron Age individuals were observed compared with the BMAC populations from Uzbekistan. Thus, despite continuity from the Bronze Age, increased admixture played a major role in the shift from the Bronze to the Iron Age in southern Uzbekistan. This mixed ancestry is also observed in other parts of the Steppe and Central Asia, suggesting more widespread admixture among local populations.

Ark shells are commercially important clam species that inhabit in muddy sediments of shallow coasts in East Asia. For a long time, the lack of genome resources has hindered scientific research of ark shells. Here, we report a high-quality chromosome-level genome assembly of Scapharca kagoshimensis, with an aim to unravel the molecular basis of heme biosynthesis, and develop genomic resources for genetic breeding and population genetics in ark shells. Nineteen scaffolds corresponding to 19 chromosomes were constructed from 938 contigs (contig N50 = 2.01 Mb) to produce a final high-quality assembly with a total length of 1.11 Gb and scaffold N50 around 60.64 Mb. The genome assembly represents 93.4% completeness via matching 303 eukaryota core conserved genes. A total of 24,908 protein-coding genes were predicted and 24,551 genes (98.56%) of which were functionally annotated. The enrichment analyses suggested that genes in heme biosynthesis pathways were expanded and positive selection of the haemoglobin genes was also found in the genome of S. kagoshimensis, which gives important insights into the molecular mechanisms and evolution of the heme biosynthesis in mollusca. The valuable genome assembly of S. kagoshimensis would provide a solid foundation for investigating the molecular mechanisms that underlie the diverse biological functions and evolutionary adaptations of S. kagoshimensis.

Wrasses are dominant components of major coral reef systems. Among wrasses, Cheilinus undulatus is an endangered species with high economic and ecological value that exhibits sex reversal of females to males, while sexual selection occurs in breeding aggregations. However, the molecular-associated mechanism underlying this remains unclear. Opsin gene diversification is regarded as a potent force in sexual selection. Here we present a genome assembly of C. undulatus, using Illumina, Nanopore and Hi-C sequencing. The 1.17 Gb genome was generated from 328 contigs with an N50 length of 16.5 Mb and anchored to 24 chromosomes. In total, 22,218 genes were functionally annotated, and 96.36% of BUSCO genes were fully represented. Transcriptomic analyses showed that 96.79% of the predicted genes were expressed. Transposons were most abundant, accounting for 39.88% of the genome, with low divergence, owing to their evolution with close species ~60.53 million years ago. In total, 567/1,826 gene families were expanded and contracted in the reconstructed phylogeny, respectively. Forty-six genes were under positive selection. Comparative genomic analyses with other fish revealed expansion of opsin SWS2B, LWS1 and Rh2. The elevated duplicates of SWS2B were generated by gene conversions via transposition of transposons followed by nonallelic homologous recombination. Amino acid substitutions of opsin paralogues occurred at key tuning sites, causing a spectral shift in maximal absorbance of visual pigment to capture functional changes. Among these opsin genes, SWS2B-3 and 4 and Rh1 are expressed in the retina. The genome sequence of C. undulatus provides valuable resources for future investigation of the conservation, evolution and behaviour of fishes.

The aim of the present study was to investigate the effect of glycosylation with sugar beet pectin (SBP) on the interfacial behaviour and emulsifying ability of coconut protein (CP). The physical stabilities of the emulsions were predicted by transmission variation, droplet distribution and zeta potentials. The results showed that SBP-CP-stabilized emulsions showed better stability during centrifugation than those stabilized by CP because SBP-CP reduced the degree of variation in the CP transmission profile. The adsorption kinetics of all emulsifiers at the oil-water interface were determined to investigate the relationship between the interfacial behaviour and emulsion stability. The presence of SBP considerably reduced the adsorption rate of CP (0.698 mN/m/s1/2) and hampered the development of a highly viscoelastic network at the oil-water interface. The values of the dilatational elastic modulus (Ed = 19.477 mN/m) and dilatational viscous modulus (E = 19.719 mN/m) were approximately equal, indicating that the adsorption process was mainly dominated by elastic behaviour. Additionally, the SBP-CP interaction enhanced the dilatational property of the CP-absorbed layer.

Optimized ultrasound-assisted extraction conditions (solid-to-liquid ratio of 1:7, ultrasonication time of 66 min, ultrasonication temperature of 55 °C and ultrasonication power of 395 W) were obtained by using response surface methodology to obtain the maximum oil yield from peony (Paeonia suffruticosa Andr.) seeds. The yield of extracted oil under optimized conditions from peony seeds in response to different harvest times ranged from 25.35 ± 1.45% to 30.85 ± 1.15% and reached a maximum 100 days after pollination (DAP). Analyses of fatty acid composition in peony seed oil by GC–MS showed that the relative contents of polyunsaturated fatty acids and α-linolenic acid were higher during the period from 95 to 105 DAP, exceeding 90% and 33% of total fatty acids, respectively, and the ratios of ω-6:ω-3 varied from 0.87:1 to 1.66:1. Moreover, the optimized extraction conditions and fatty acid characteristics of peony seed oil in different harvest time periods may be used as important references for the industrialization of peony and harvest time of peony seeds in the future.

The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1−/−) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1−/−-OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1−/−-OVA group and TRPA1−/−-OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3′-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3′-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3′-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.

Grapevine (Vitis spp.) is one of the most economically important fruit crops worldwide, and there is considerable interest in improving its major agronomic and enological traits in response to ever-changing agricultural environments and consumer demands. Molecular genetic techniques in particular, associated with rapid technological advancements, provide an attractive alternative to conventional breeding approaches for developing new grapevine varieties with enhanced yield performance, quality, stress tolerance and disease resistance. To date, several grapevine varieties have been transformed with genes associated with diverse functions through biolistic bombardment and/or Agrobacterium-mediated transformation, and transgenic grape lines have been obtained using established regeneration systems. Nevertheless, a wide range of factors, including genotype, explant source and culture medium, have been shown to affect the efficiency of plant regeneration. Moreover, the selection and use of acceptor materials, bacterial strain and cell density, selectable markers and selection methods also influence transformation efficiency. This paper provides an overview of recent advances in grapevine regeneration and genetic transformation and in-depth discussion of the major limiting factors, and discusses promising future strategies to develop robust plant regeneration and genetic transformation in grapevine.

Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease and even blindness in newborns. However, ZIKV-induced retinal lesions have not been studied in a comprehensive way, mechanisms of ZIKV-induced retinal abnormalities are unknown, and no therapeutic intervention is available to treat or minimize the degree of vision loss in patients. Here, we developed a novel mouse model of ZIKV infection to evaluate its impact on retinal structure. ZIKV (20 plaque-forming units) was inoculated into neonatal wild type C57BL/6J mice at postnatal day (P) 0 subcutaneously. Retinas of infected mice and age-matched controls were collected at various ages, and retinal structural alterations were analyzed. We found that ZIKV induced progressive neuronal and vascular damage and retinal inflammation starting from P8. ZIKV-infected retina exhibited dramatically decreased thickness with loss of neurons, initial neovascular tufts followed by vessel dilation and degeneration, increased microglia and leukocyte recruitment and activation, degeneration of astrocyte network and gliosis. The above changes may involve inflammation and endoplasmic reticulum stress-mediated cell apoptosis and necroptosis. Moreover, we evaluated the efficacy of preclinical drugs and the safety of ZIKV vaccine candidate in this mouse model. We found that ZIKV-induced retinal abnormalities could be blocked by a selective flavivirus inhibitor NITD008 and a live-attenuated ZIKV vaccine candidate could potentially induce retinal abnormalities. Overall, we established a novel mouse model and provide a direct causative link between ZIKV and retinal lesion in vivo, which warrants further investigation of the underlying mechanisms of ZIKV-induced retinopathy and the development of effective therapeutics. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01195-6.

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals. In this study, using a FcRn knockout pig model generated with a CRISPR-Cas9-based approach, we clearly demonstrate that FcRn is not responsible for the IgG transfer from serum to colostrum in pigs, although like in other mammals, it is involved in IgG homeostasis and mediates IgG absorption in the small intestine of newborns.

Age at onset of amyotrophic lateral sclerosis (ALS) is highly variable (eg, 27–74 years in carriers of the G4C2-expansion in C9orf72). It might be influenced by environmental and genetic factors via the modulation of DNA methylation (DNAm) at CpG-sites. Hence, we combined an epigenetic and genetic approach to test the hypothesis that some common single nucleotide polymorphisms (SNPs) at CpG-sites (CpG-SNPs) could modify ALS age of onset. Our genome-wide DNAm analysis suggested three CpG-SNPs whose DNAm levels are significantly associated with age of onset in 249 ALS patients (q C9orf72-carriers (n = 333; P = 0.025), suggesting that each A-allele delays onset by 1.6 years. Analysis of Genotype-Tissue Expression data revealed that the protective A-allele is linked with the reduced expression of CTSS in cerebellum (P = 0.00018), which is a critical brain region in the distributed neural circuits subserving motor control. CTSS encodes cathepsin S protein playing a key role in antigen presentation. In conclusion, we identified a 16 Kb locus tagged by rs4970944 as a modifier of ALS age of onset. Our findings support the role of antigen presenting processes in modulating age of onset of ALS and suggest potential drug targets (eg, CTSS). Future replication studies are encouraged to validate the link between the locus tagged by rs4970944 and age of onset in independent ALS cohorts, including different ethnic groups.

Supplemental Digital Content is Available in the Text., Acute immune rejection is one of the most serious complications of heart transplantation, and its mechanism has always been a hot spot. Th17 cells and cytokine interleukin-17 (IL-17) have been proved to be involved in acute immune rejection, and the signaling pathway mechanism has attracted our interest. It has been confirmed that the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the differentiation of CD4+ T cells, so we focus on whether the JAK2/STAT3 signaling pathway is involved in the occurrence of acute immune rejection by regulating the Th17/IL-17 axis. In this study, we used Bagg’s Albino c mice and C57BL/6 mice to construct heterotopic heart transplantation models, which were divided into the acute rejection group and AG490-treated group (n = 5), and donor tissue and serum were collected in 3 experimental days from the recipient mice for H&E staining analysis of paraffin sections and ELISA, Western blot, flow cytometry, and real time-polymerase chain reaction. The results showed that the acute rejection rating of the heart decreased, and the expression of related factors decreased significantly after using the inhibitor AG490, suggesting that the JAK2/STAT3 signaling pathway regulates expression of the Th17/IL-17 axis in cardiac allograft rejection.

Long noncoding RNA (LncRNA) dysregulation has been shown to exhibit a regulatory effect in various cancers. However, the effect of LINC01287 on breast cancer (BC) has not been illustrated. The aim of this research was to explore the expression and function of LncRNA LINC01287 in BC. LINC01287 expression in clinical tissues and BC cell lines was detected. The luciferase reporter assay was performed to verify the correlation between LINC01287, microRNA 98 (miR-98), and the insulin-like growth factor 1 receptor (IGF1R). The CCK-8 assay was performed to examine cell viability. Cell invasion and migration capacity was determined by transwell and wound healing assays. The protein level of IGF1R, phosphorylated mitogen-activated protein kinase 1 and 2 (p-MEK1/2), and phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) was analyzed by western blotting. LINC01287 expression markedly increased in BC cell lines. Subsequent studies identified LINC01287 as a downstream target of miR-98. In addition, LINC01287 knockdown and miR-98 overexpression significantly stagnated progression of BC cells. LINC01287 knockdown also downregulated IGF1R levels. Moreover, LINC01287 knockdown notably downregulated the phosphorylation of MEK1/2 and ERK1/2. The in vivo assay verified that LINC01287 can regulate tumorigenesis of BC. Our findings showed that LINC01287 was overexpressed in BC cells and tissues. LINC01287 promoted the malignant characteristics of BC cells and acted as an oncogene. Its regulatory effect may be associated with the miR-98/IGF1R/MEK/ERK signaling pathway. Therefore, LINC01287 has potential for use as a biomarker or therapeutic target for the treatment of BC.

Background MicroRNAs play an important role in many fundamental biological and pathological processes. Defining the microRNAs profile underlying the processes by beneficial and detrimental lifestyles, including caloric restriction (CR), exercise and high-fat diet (HF), is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We used the microarray to detect microRNAs expression in livers from CR, EX and HF mice models. After predicted potential target genes of differentially expressed microRNAs with four algorithms, we applied GO and KEGG to analyze the function of predicted microRNA targets. Results We describe the overall microRNAs expression pattern, and identified 84 differentially expressed microRNAs changed by one or two or even all the three lifestyle modifications. The common and different enriched categories of gene function and main biochemical and signal transduction pathways were presented. Conclusions We provided for the first time a comprehensive and thorough comparison of microRNAs expression profiles in liver among these lifestyle modifications. With this knowledge, our findings provide us with an overall vision of microRNAs in the molecular impact of lifestyle on health as well as useful clues for future and thorough research of the role of microRNAs.

BackgroundAlternative polyadenylation (APA) is an important mechanism of gene expression regulation through generation of RNA isoforms with distinct 3′ termini. Increasing evidence has revealed that APA is actively involved in development and disease, including hepatocellular carcinoma (HCC). However, how APA functions in tumor formation and progression remains elusive. In this study, we investigated the role of cleavage factor I (CFIm) subunit CPSF6 in human hepatocellular carcinoma (HCC).MethodsExpression levels of CPSF6 in clinical tissues and cell lines were determined by qRT-PCR and western blot. Functional assays, including the cell number, MTT, colony formation and transwell, were used to determine the oncogenic role of CPSF6 in HCC. Animal experiments were used to determine the role of CPSF6 in HCC tumorigenicity in vivo. Deep sequencing-based 3 T-seq was used to profile the transcriptome-wide APA sites in both HCC cells and CPSF6 knockdown HCC cells. The function of CPSF6-affected targetNQO1with distinct 3′UTRs was characterized by metabolism assays.ResultsWe observed CPSF6 was upregulated in HCC and the high expression of CPSF6 was associated with poor prognosis in patients. Overexpression of CPSF6 promoted proliferation, migration and invasion of HCC cells in vitro and in vivo. Transcriptome-wide APA profiling analysis indicated that high expression of CPSF6 promoted the favorable usage of the proximal poly(A) site in the 3′UTR ofNQO1. We demonstrated CPSF6-induced tumorigenic activities were mediated by theNQO1isoform with short 3′UTR. Furthermore, we found that CPSF6 induced metabolic alterations in liver cells through NQO1.ConclusionCPSF6 plays a critical role in HCC progression by upregulating NQO1 expression through APA. These findings provide evidence to demonstrate that APA ofNQO1contributes to HCC progression and may have implications for developing new therapeutic strategy against this disease.

Probiotics have been reported to be associated with the alleviation of constipation. The aim of this study was to detect and determine the effect of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) on the alleviation of constipation in BALB/c mice and humans, and to elucidate the mechanisms underlying its effect by measuring changes in the concentration of short-chain fatty acids and the composition of microbes in human faeces. BALB/c mice were given MN-Gup by gavage for 14 days. On the 8th day of this treatment, constipation was induced by the application of diphenoxylate via gavage. The results showed that MN-Gup significantly decreased the first black stool defecation time, and significantly increased black faecal wet weight, black faecal number and the gastric-intestinal transit rate (P

DNA replication stress poses a severe threat to genome stability and is a hallmark of cancer as well as a target for cancer therapy. It is well known that the evolutionarily conserved protein kinase WEE1 regulates replication stress responses by directly phosphorylating and inhibiting the major cell cycle driver CDKs in many organisms. Here, we report a novel WEE1 pathway. We found that Arabidopsis WEE1 directly interacts with and phosphorylates the E3 ubiquitin ligase FBL17 that promotes the degradation of CDK inhibitors. The phosphorylated FBL17 is further polyubiquitinated and degraded, thereby leading to the accumulation of CDK inhibitors and the inhibition of CDKs. In strong support for this model, either loss of function of FBL17 or overexpression of CDK inhibitors suppresses the hypersensitivity of the wee1 mutant to replication stress. Intriguingly, human WEE1 also phosphorylates and destabilizes the FBL17 equivalent protein SKP2, indicating that this is a conserved mechanism. This study reveals that the WEE1-FBL17/SKP2-CKIs-CDKs axis is a molecular framework for replication stress responses, which may have clinical implications because the WEE1 inhibitor AZD1775 is currently in phase II clinical trial as an anticancer drug. The kinase WEE1 regulates replication stress responses by directly phosphorylating cell cycle driver CDKs. Now, WEE1 is found to regulate CDKs via an indirect pathway involving the E3 ligase FBL17 and CDK inhibitors, a mechanism probably shared between plants and humans.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

The sex determination and control of poultry is a key problem in production and scientific research despite few studies on regulatory factors, especially transcription factors in sex determination. In the early stage of this study, high-throughput sequencing was used to screen the differentially expressed gene JUN in male and female embryonic stem cells (ESCs) and primordial germ cells (PGCs). The qRT-PCR discovered that the JUN gene significantly increased from embryonic days (E) 2.5 later in chicken embryo development, and the female gonad expression was much higher than that of the male after E14.5. Lentivirus shRNA-JUN, shRNA-Smad2 interference, and OE-JUN overexpression vectors were successfully constructed. After interfering with JUN in vivo, male characteristics appeared in ZW embryonic gonads at E18.5. Meanwhile, the male-specific genes DMRT1 and Sox9 were upregulated, the female-specific genes FOXL2, ESR1, and CYP19A1 were downregulated, and the estradiol in the gonads was significantly decreased. The situation was reversed after the overexpression of JUN, ZZ chicken embryo developed into female sexual characteristics. The double luciferase report has found that the Smad2 promoter activity was significantly upregulated after interference with JUN, and significantly increased after the deletion of the JUN binding site. After the injection of the Smad2-shRNA vector into the blood vessel in vivo, it was discovered that DMRT1 and Sox9 of ZW embryos at E18.5 were downregulated, FOXL2 and CYP19A1 were significantly upregulated, and the gonads show femininity. In conclusion, this study proves that JUN is a key regulator in the process of chicken female sex differentiation, which can inhibit the transcription of Smad2 and promote the synthesis of estradiol, and participate in the process of chicken sex differentiation. This study lays a foundation for the analysis of the molecular mechanism of chicken sex determination and the development of poultry sex control technology.

Three unprecedented oligomeric phenylpropanoids with new carbon skeletons [(+)/(–)-maglignan A ((+)/(–)-1) and maglignan B (2)] and an undescribed meroterpenoid [maglignan C (3)] possessing an oxabicyclo [3.3.1] skeleton were obtained from the bark of Magnolia officinalis var. biloba. Compounds (+)-1 and (–)-1, a pair of enantiomeric trimers with novel oligomerization mode, which could be biosynthesized through oxidation, substitution, and hetero-Diels–Alder (HDA) reactions between C6–C3 units, exhibited significant inhibition of PTP1B and α-glucosidase with IC50 values from 0.448 to 2.16 μM. Molecular docking simulation was conducted to demonstrate the obtained results.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 μmol/L vs. 325.60 ± 18.65 μmol/L, p

Gender research shows excellent significance in the breeding and production of poultry, achieving the actual needs of poultry through targeted gender regulation could increase economic benefits. Ho...

Background Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer’s disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. Methods The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis was conducted to explore the underlying pathological mechanisms. Results Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut–brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. Conclusion Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome–gut–brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.

DNA studies of endangered or extinct species often rely on ancient or degraded remains. The majority of ancient DNA (aDNA) extraction protocols focus on skeletal elements, with skin and hair samples rarely explored. Similar to that found in bones and teeth, DNA extracted from historical or ancient skin and fur samples is also extremely fragmented with low endogenous content due to natural degradation processes. Thus, the development of effective DNA extraction methods is required for these materials. Here, we compared the performance of two DNA extraction protocols (commercial and custom laboratory aDNA methods) on hair and skin samples from decades-old museum specimens to Iron Age archaeological material. We found that apart from the impact sample-specific taphonomic and handling history has on the quantity and quality of DNA preservation, skin yielded more endogenous DNA than hair of the samples and protocols tested. While both methods recovered DNA from ancient soft tissue, the laboratory method performed better overall in terms of DNA yield and quality, which was primarily due to the poorer performance of the commercial binding buffer in recovering aDNA.